Handbook of Active Marine Natural Products: Volume 1 Terpenoids, Part 1 9783110655131, 9783110653243

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Jiaju Zhou Handbook of Active Marine Natural Products

Handbook of Active Marine Natural Products Jiaju Zhou Volume : Terpenoids, Part  ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Volume : Alkaloids, Part  ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Volume : Alkaloids, Part  ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Volume : Polyketides and Steroids ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Volume : Aliphatic Metabolites ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Volume : O-Heterocycles and Aromatics ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Volume : Peptides and Others ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Jiaju Zhou

Handbook of Active Marine Natural Products Volume 1: Terpenoids, Part 1

Author Prof. Jiaju Zhou Chinese Academy of Sciences 1303 Department, 10 Building 31 Zhong Guan Cun Nan Dajie 100081 Beijing China [email protected]

ISBN 978-3-11-065324-3 e-ISBN (PDF) 978-3-11-065513-1 e-ISBN (EPUB) 978-3-11-065331-1 Library of Congress Control Number: 2019941348 Bibliographic information published by the Deutsche Nationalbibliothek The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at http://dnb.dnb.de. © 2019 Walter de Gruyter GmbH, Berlin/Boston Typesetting: Integra Software Services Pvt. Ltd. Printing and binding: CPI books GmbH, Leck Cover image: Science Photo Library/Douwma, Georgette www.degruyter.com

Preface The English edition Handbook of Active Marine Natural Products (HAMNP) with 8 Volumes is a selective version of the Marine Natural Products Dataset. The whole dataset was collected and developed by the Molecular Design Group, Institute of Process Engineering, Chinese Academy of Sciences during 1998–2016. Totally, it covers 19,722 entries of secondary metabolites from marine living things, where 8,350 compound entries have pharmacological activity data. The 8,350 compound entries were grouped into eight volumes to form the set of handbooks as follows: Volume 1: Terpenoids, Part 1 Volume 2: Terpenoids, Part 2 Volume 3: Alkaloids, Part 1 Volume 4: Alkaloids, Part 2 Volume 5: Polyketides and Steroids Volume 6: Aliphatic Metabolites Volume 7: O-Heterocycles and Aromatic Volume 8: Peptides and Others This set of eight HAMNP books gathers the structure, origin, and bioactivity, as well as other relevant information, of 8,350 active marine natural products from 3,025 marine organisms. The HAMNP handbook represents a largest collection of active secondary metabolites from marine organisms, and all kinds of scientific data have been reorganized as well-formatted data so that the books became helpful to researchers as a convenient reference. The materials covered in these books include those through systematic collection up to 2012, and further accompanied with the latest data published in several core journals until 2016. The work covered in these HAMNP books was accomplished in two phases. The initial phase ranged from 1998 to 2001 and the main phase from 2011 to 2018. In the original version of the dataset, more than 22,000 compounds have been collected, including duplicated compounds from different authors. The comprehensive data compilation process include data specification definition, cross-validation, assessment confirmation, identification of duplicated structures, and merging of relevant information, leading to the final accomplishment of the current 19,722 datasets. In brief, the main compilation process of the HAMNP books is given as follows. First, collect the name list, origin, and structure of chemical compounds from successive annual reviews (see Core References R01 and R02 in Introduction) and literature reviews. Second, double-check the documents to verify and complete other information. Third, confirm the structural information and other types of data using orthogonal information from other sources with cross-validation methods. Fourth, the structures of more than 22,000 compounds are rechecked and the information is integrated by manual identification and computer programs. Finally, the comprehensive information https://doi.org/10.1515/9783110655131-201

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on the 19,722 compounds constitutes the dataset. Here, 8,350 active sets were picked up from the dataset to form the current HAMNP handbook. Three problems need to be solved to compile a multidisciplinary reference book. First, every definition and concept should be explicit when expanding knowledge, connotation and extension included, without any research details. Second, the reliability assessment is essential for all kinds of data, because the devil is in the detail. Third, it is essential to search, identify, and integrate data of duplicated chemical compounds. Fortunately, well-developed software packages can help us automatically identify the majority of duplicated chemical compounds. The remaining issues can be resolved by combining with manual processing. It is the guiding principle of the author to make the book to be pithy, thorough, precise, and intelligible. In fact, we always view ourselves as HAMNP’s readers, with the exclusive objective to let readers gain the most useful knowledge in the shortest possible time. The core contents and highlights of the HAMNP books are the “three diversities,” that is, the diversity of chemical structures, the diversity of biological resources, and the diversity of pharmacological activities. In terms of chemical structure diversity, we refer to the classification system from references, then further improve and expand it based on the latest research and development to define our classification framework of structures. Once readers browse the contents of the books, the classification system is straightforward. For the diversity of biological resources, it is recommended to refer to Index 3 in each volume – Compound Marine Organism Source Index; and Index 4 in each volume – Compound Marine Source Sampling Geographic Location Index. For the diversity of Pharmacological activities, it is recommended to refer to Index 5 in each volume – Compound Pharmacological Activity Index. These HAMNP handbooks are expected to help readers who are engaged in research, in teaching, and in the development of marine natural products. It should also benefit college students, postgraduates, marine resource managers, and those who are interested in the chemistry and pharmacology of marine natural products. We would feel fortunate if it works as expected.

Jiaju Zhou Institute of Process Engineering (IPE), Chinese Academy of Sciences (CAS) February 2019

Contents Preface V About the Author IX Introduction XI How to Use the HAMNP Books XIX List of Abbreviations and Acronyms XXIII List of Cancer Cell Codes XXXIII 1

Monoterpenoids 1 1.1 Acyclic Monoterpenoids 1 1.2 Halogenated Dimethyloctane Monoterpenoids 2 1.3 Ochtodane Monoterpenoids 8 1.4 1-Ethyl-1,3-Dimethylcyclohexane Monoterpenoids 10 1.5 1-Ethyl-2,4-Dimethylcyclohexane Monoterpenoids 13 1.6 Iridoid Monoterpenoids 14 1.7 Menthane Monoterpenoids 15

2

Sesquiterpenoids 17 2.1 Farnesane Sesquiterpenoids 17 2.2 Cyclopentane Sesquiterpenoids 25 2.3 Irregular Acyclic Sesquiterpenoids 26 2.4 Bisabolane Sesquiterpenoids 26 2.5 Elemane Sesquiterpenoids 35 2.6 Germacrane Sesquiterpenoids 36 2.7 Miscellaneous Monocyclic Sesquiterpenoids 2.8 Caryophyllane Sesquiterpenoids 38 2.9 Cuparane Sesquiterpenoids 39 2.10 Laurane Sesquiterpenoids 40 2.11 Trichothecane Sesquiterpenoids 42 2.12 Eudesmane Sesquiterpenoids 45 2.13 Eremophilane Sesquiterpenoids 51 2.14 Nardosinane Sesquiterpenoids 56 2.15 Cadinane Sesquiterpenoids 58 2.16 Drimane Sesquiterpenoids 61 2.17 Guaiane Sesquiterpenoids 71 2.18 Aromadendrane Sesquiterpenoids 75 2.19 Valerenane Sesquiterpenoids 77 2.20 Illudalane Sesquiterpenoids 78 2.21 Furodysinin Sesquiterpenoids 79 2.22 Chamigrane Sesquiterpenoids 80 2.23 Sativane Sesquiterpenoids 88

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2.24 2.25 2.26 2.27 2.28 2.29 2.30 2.31 2.32 2.33 3

Other Bicyclic Sesquiterpenoids 89 Africanane Sesquiterpenoids 97 Capnellane Sesquiterpenoids 97 Hirsutane Sesquiterpenoids 101 Silphiperfoliane Sesquiterpenoids 102 Quadrane Sesquiterpenoids 102 Precapnellane Sesquiterpenoids 103 Hamigerane Sesquiterpenoids 104 Miscellaneous Tricyclic Sesquiterpenoids Fourcyclic Sesquiterpenoids 110

108

Diterpenoids 113 3.1 Phytane Diterpenoids 113 3.2 10,15-Cyclophytane Diterpenoids 118 3.3 Linear Homo- and Nor- diterpenoids 122 3.4 Labdane Diterpenoids 123 3.5 Halimane Diterpenoids 129 3.6 Clerodane Diterpenoids 133 3.7 Isopimarane Diterpenoids 147 3.8 Dolabrane (Erythroxylane) Diterpenoids 156 3.9 Paraguerane and Isoparguerane Diterpenoids 3.10 Spongiane Diterpenoids 159 3.11 Podocarpane Diterpenoids 174 3.12 Phyllocladane Diterpenoids 174 3.13 Cembrane Diterpenoids 176 3.14 Pseudopterane Diterpenoids 260 3.15 Eunicellane diterpenoids 265 3.16 Asbestinane diterpenoids 315 3.17 Sphaerane diterpenoids 318 3.18 Briarane diterpenoids 319

Index 1 Index 2 Index 3 Index 4 Index 5

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Compound Name and Synonym Index 395 Compound Molecular Formula Index 411 Compound Organism Source Index 430 Compound Sampling Geographic Locality Index 437 Compound Pharmacological Activity Index 441

About the Author Prof. Jiaju Zhou was born in October 1939 in Tianjin, China. He graduated from Rare Earth Inorganic Chemistry Specialty, Chemistry Department, Peking University, in 1963 under a six-year program. Before he retired in 2008, Zhou was the leader of Molecule Design Group, IPE, CAS. Zhou’s areas of research include rare earth chemistry, mineral analytical chemistry, chemical industry process simulation (in IPE, CAS and UBC, Canada), design of crystal structural database (in OSRD, NIST, Gaithersburg, MD, USA), scientific database R&D, and computer-aided and artificial intelligence drug design. Zhou developed the first TCM database (TCMDB) with 23,033 entries. Since 2008, he has worked on Marine Natural Products project and has developed the Marine Natural Products Database (MNPDB) with 19,722 entries.

https://doi.org/10.1515/9783110655131-202

Introduction The Handbook of Active Marine Natural Products covers eight volumes. This book is Volume 1: Terpenoids, Part 1, which includes 1,131 active compounds. Format of Compound Entry. A compound entry starts with a title line, which has two items: the compound’s unique code (from 1 to 1,131 for volume 1) and the main name. The following eight items form the title line as a body, and the graphic structure is placed at the end: Title line (code number, main name) A. Synonyms of the compound (if any) B. Structural type C. Formula (relative molecular mass) D. Physicochemical properties E. Marine source(s) F. Pharmacological data (if any) G. Reference(s) Graphic structure Chemical Names and A. Synonyms. Generally, a compound may have one scientific name and several trivial names. In the handbooks, based on original articles, we select one name as the “main name.” The main name appeared at the title line of each compound entry. In most cases, a trivial name was selected as the main name, and in some cases, the main name is a scientific name. Any synonyms, if any, are presented after the title line as an item A of the entry body. B. Structural Type. Structural type is the second item, ordered by the contents order. F. Normalization of Pharmacological Data. All of 1,131 MNP components in this book have pharmacological data, which are very valuable. Because different expressions are used for the same kind of data in different articles, we have to define and normalize thousands of pharmacological terms, so that the data could be expressed in a unified way, and be easily understood by readers. Stereochemistry in Graphic Structure. We protracted all compound structures down to atomic bond level, including complicated glycosides, with stereochemical information based on the data in the original papers. For example, the structure with full stereochemistry of the compound 730 sinularin is OH

O

O

H

O https://doi.org/10.1515/9783110655131-203

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Let us further explain the data structure of source terms and pharmacological terms.

Source Terms The source data of the compound 730 sinularin is Source: Soft coral Sinularia sp. (Dongluo I. Hainan, South China Sea) Soft coral Sinularia triangula (Taitung County, Taiwan) Soft coral Sinularia flexibilis Soft coral Sinularia capillosa The format is as follows (banding the English-type name and the Latin name together): Source: English-type name + Latin name of source 1 (sampling place, sampling season water depth, etc., if any) English-type name + Latin name of source 2 English-type name + Latin name of source 3 English-type name + Latin name of source 4

Pharmacological Terms The pharmacological terms in the handbooks are presented in a multilayered structure. In the top layer, there are more than 20 types of the most important pharmacological activity terms. They are cytotoxic (in vitro anticancer), antineoplastic (in vivo anticancer), antibacterial, antifungal, antiviral, anti-HIV, anti-inflammatory, antioxidant, antimalarial, NO (nitric oxide) production inhibitors, enzyme inhibitors, cardiovascular activity, smooth muscle relaxant and stimulant, toxin and medium lethal dose (LD50), and so forth. Readers need to be familiar with these Tope lever pharmacological terms (see Table 1). For each term there is a regulation about how to describe related pharmacological data. The following is an example. Under the subtitle “Pharm:” of the compound 730 Sinularin, a set of multiple biodata is presented as follows: Pharm: Cytotoxic (CCRF-CEM, ED50 = 26.0 μmol/L, control doxorubicin, ED50 = 0.57 μmol/ L, DLD-1, ED50 = 37.1 μmol/L, doxorubicin, ED50 = 0.25 μmol/L); anti-inflammatory [immunoblot analysis assay, 10 μmol/L, RAW264.7 macrophage cells, inhibition of LPS-induced upregulation of iNOS and COX-2, reduced COX-2 to ≈ 85%, reduced iNOS to (1.2 ± 0.3)%];

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Table 1: Twenty-Four Main Pharmacological Terms in Tope Lever. Order in Index 

Pharmacological Terms in Tope Lever

                       

Anti-AD Antibacterial Antifungal Anti-HIV Anti-inflammatory Antileishmanial Antimalarial Antineoplastic (in vivo) Antioxidant Antiplasmodial Antitrypanosomal Antituberculosis Antiviral Cardiovascular activity Cell cycle inhibitor Cell division inhibitor Cell growth inhibitor Cell adhesion inhibitor Cytotoxic (in vitro) Enzyme inhibitors NO production inhibitors Smooth muscle relaxant and stimulant Toxin Medium lethal dose (LD)

antibacterial (gram-positive bacteria); NF-κB inhibitor (cell-based HEK-293 NF-κB luciferase reporter gene assay, IC50 = 5.30 μg/mL; NF-κB plays a key role in regulating immune response to infection, incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development). The format is as follows: Pharm: Term name 1 (formatted detail information) Term name 2 (formatted detail information) Term name 3 (formatted detail information) Term name 4 (formatted detail information)

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Under the term name Cytotoxic, a set of multiple cytotoxic biodata is presented as follows: Cytotoxic CCRF-CEM, ED50 = 26.0 μmol/L, control doxorubicin, ED50 = 0.57 μmol/L, DLD-1, ED50 = 37.1 μmol/L, control doxorubicin, ED50 = 0.25 μmol/L; The format is as follows: Term name (in vitro/in vivo, target cancer cell 1, quantitative data, positive control compound, control’s quantitative data (if any); target cancer cell 2, quantitative data, positive control compound, control’s quantitative data (if any); brief description of related mechanism if any). In order to standardize abbreviations of cancer cells, such as P388, A549, HT29, MEL28, CCRF-CEM, and DLD-1, we defined and used 438 cancer cell codes (CCC) in the handbooks. For explanations of these codes, please see “List of Cancer Cell Codes.” By means of the formatted and structuralized methods, we have normalized expressions of almost all the pharmacological data discussed in the handbooks. For complete information in volume 1, of all 674 normalized pharmacological activity terms, please see “Index 5 Compound Pharmacological Activity Index.” In summary, these handbooks with eight volumes provide an integrated collection of 8,350 marine natural products’ chemical components isolated from 3,025 marine organisms and a large amount of pharmacological activity data of these components. It might be used not only as a handbook to look for structures and bioactivities of marine natural products and marine organisms source information, but also as a fundamental platform for studying the marine natural products with a systematic and integrative approach.

Acknowledgments First, as the author of those books, I would like to give my heartfelt thanks to Dr. David Lide and B.J. Lide, who were my directors 30 years ago when I worked in OSRD, NIST (former NBS), USA, in 1985–1986 for nine months. They gave me the rare opportunity to learn how to use a software platform and how to treat a complicated scientific information data system. It is my research experience in NBS that helped me to compile easily the current huge project in Marine Natural Products. At the same time, I also give my sincere thanks to my NBS’s colleagues: Dr. John Rumble, Mrs. Geraldine Dalton, Mrs. Phoebe Fagan, and other OSRD members.

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Then, I would like to give my genuine thanks to the following two close friends. They two gave my MNP project continual concerns and supports for years: Dr. Jun Xu, Professor and Director, Research Center for Drug Discovery, Sun Yet-Sen University, 132 East Circle, University City, Guangzhou 510006, China, and Dr. Leming Shi, Professor and Director, Center for Pharmacogenomics, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai 200438, China ([email protected]). Third, I like to give my honest thanks to my following group members. For many years, all of them gave various devices to me: 1 Dr. Jing Lei, Associate Professor, Educational Equipment Research and Development Centre, Ministry of Education of the People’s Republic of China, Beijing 100080, China (early research in her doctor thesis) 2 Dr. Bing Liu, Lead Dev Prophix Software Inc. 350 Bumhamthorpe Road West, Suite 1000 Mississauga, Ontario L5B 3J1, Canada (data collection in the early stage) 3 Master Yingxin Qiao, Software Engineer, National Library of China, Beijing 100081, China (data source searching and original paper collection) 4 Dr. Haibo Liu, Associate Professor, The Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 100193, China (special software development for automatic edition) 5 Dr. Tao Peng, Associate Professor, College of Robotics, Beijing Union University, Beijing 1001011, China (special software development for index generation) 6 Dr. Aihua Xie, Associate Professor, School of Pharmacy, Hebei Chinese Medical University, Shijiazhuang, Hebei 050200, China (part of data collection) 7 Dr. Chenzhong Liao, Professor, Dean of Department of Pharmacy, School of Biological and Medical Engineering, Hefei University of Technology, Hefei 230009, China (original paper collection) 8 Dr. Jianfeng Pei, Associate Professor, Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China (data collection in early stage); 9 Dr. Xianfeng He, Associate Professor, Scientific Researcher, EMMS Group, State Key Laboratory of Multiphase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China (data collection in the early stage) 10 Madam Guirong Xie, Associate Professor, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China (part of data compilation) 11 Mr. Wucheng Tang, Engineer, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China (part of original paper collection). Finally, I thank my family members. Without their complete and never-ending support, this book would never have been possible.

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Core References (Guiding References 5) R01 D. J. Faulkner, Marine Natural Products (review), Nat. Prod. Rep., 1986, 3, 1–33; 1987, 4, 539–576; 1988, 5, 613–663; 1990, 7, 269–309; 1991, 8, 97–147; 1992, 9, 323–364; 1993, 10, 497–539; 1994, 11, 355–394; 1995, 12, 223–269; 1996, 13, 75–125; 1997, 14, 259–302; 1998, 15, 113–158; 1999, 16, 155–198; 2000, 17, 7–55; 2001, 18, 1R–49R; 2002, 19, 1–49 R02 J. W. Blunt, et al, Marine Natural Products (review), Nat. Prod. Rep., 2003, 20, 1–48; 2004, 21, 1–49; 2005, 22, 15–61; 2006, 23, 26–78; 2007, 24, 31–86; 2008, 25, 35–94; 2009, 26, 170–244; 2010, 27, 165–237; 2011, 28, 196–268; 2012, 29, 144–222; 2013, 30, 237–323; 2014, 31, 160–258; 2015, 32, 116–211 R03 J. Buckingham (Executive Editor), Dictionary of Natural Products, Chapman & Hall, London, Vol. 1–Vol. 7 1994; Vol. 8, 1995; Vol. 9, 1996; Vol. 10, 1997; Vol. 11, 1998 R04 CRC Press, Dictionary of Natural Products on DVD, version 20.2, 2012 R05 Jean-Michel Kornprobst, Encyclopedia of Marine Natural Products, Vol. 1–Vol. 3, 2nd Edition, WILEY BLACKWELL, Germany, 2014

(Dictionaries 17) R06 P.M. Kirk, P.F. Cannon, D.W. Minter and J.A. Stalpers, Dictionary of the Fungi, 10th Edition, CABI Europe-UK, 2011 R07 Miaoying Cai, et al., Names of Bacteria, 2nd Edition, Science Press, Beijing, 1996 R08 Rui-Fu Yang et al, Dictionary of Bacterial Names with English Explanation and Chinese Translation, Chemical Industry Press, Beijing, 2011 R09 Zongxun Wang et al. (Institute of Botany, Chinese Academy of Sciences), New Edited Plant Names in Latin-Chinese-English, Aerial Industry Press, Beijing, 1996 R10 Zhong-Yan Qi and Xi-Xing Liu, New Names of Invertebrate Animals in Latin-Chinese, Science Press, Beijing, 1999 R11 Ling-Ti Lu and Jia-Ran Zhu, Dictionarium Lantino-Sinicum de Scientia et technologia, The Commercial Press, Beijing, 2017 R12 Ji-Sheng Chen, et al., English-Chinese Dictionary of Life Science, Scientific and technological Literature Press, Beijing, 1992 R13 P. Singleton and D. Sainsbury (Qing-jun Ma and Cheng-hua Shi et al. translated), Dictionary of Microbiology and Molecular Biology, Chemical Industry Press, Beijing, 2008 R14 Scientific Terms Laboratory of Science Press, English-Chinese Dictionary of Chemistry and Chemical Engineering, 4th Edition, Science Press, Beijing, 2000 R15 Scientific Terms Laboratory of Science Press, English-Chinese Dictionary of Chemistry and Chemical Engineering, 5th Edition, Science Press, Beijing, 2016 R16 Jian Zhuge and Zheng-Xiang Wang, Modern English-Chinese Dictionary of Biotechnology, Science Press, Beijing, 2003 R17 Jing-Ying Tan, English-Chinese Biological Dictionary of Biochemistry and Molecular Biology, 2nd Edition, Science Press, Beijing, 2007 R18 Scientific Terms Laboratory of Science Press, English-Chinese Biological Dictionary, 2nd Edition, Science Press, Beijing, 1997 R19 Scientific Terms Laboratory of Science Press, Chinese-English Biological Dictionary, 2nd Edition, Science Press, Beijing, 1998

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R20 Yu Hui, A New Century Chinese-English Dictionary, Foreign Language Teaching and Research Press, Beijing, 2003 R21 Zong-Guo Huang and Mei-Ling Jin, Dictionary of Marine Biology, Ocean Press, Beijing, 1994 (in Chinese) R22 Wenbao Chang, et al., Dictionary of Chemistry, Science Press, Beijing, 2008 (in Chinese)

(Book References 11) R23 Hua-Shi Guan and Shu-Guang Wang, Zhong-hua Hai-yang Ben-cao, Marine Natural Products, 3 Volumes, Chemical Industry Press and Shanghai Science and Technology Press, Beijing, 2009 (in Chinese) R24 C. J. Alexopoulos, M. Blackwell and C. W. Mims, (Yijian Yao and Yu Li translated), Introductory Mycology, Fourth Edition, John Wiley & Sons, Inc., 1996, Chinese Agricultural Press, Beijing, 2002 R25 Janet S. Dodd, The ACS Style Guide, A Manual for Authors and Editors, 2nd Edition, American Chemical Society, Washington, DC, 1997 R26 Shu-Xian Ren, Invertebrates, 2 volumes, Peking University Press, Beijing, 1990 (in Chinese) R27 R. Mcneill Alexander, (translated by Lan-zhi Du), The invertebrates, Chemical Industry Press, Beijing, 2013 (in Chinese) R28 Yanghua Yi and Binghua Jiao, Modern Marine pharmacology, Science Press, Beijing, 2006 (in Chinese) R29 Chang-Yun Wang and Chang-Lun Shao, Marine pharmacology, Science Press, Beijing, 2011 (in Chinese) R30 Rensheng Xu, et al., Chemistry of Natural Products, 2nd Edition, Science Press, Beijing, 2004 (in Chinese) R31 Yue-Zeng Chen, General Biology, Higher Education Press, Beijing, 1997 (in Chinese) R32 Jiaju Zhou, Guirong Xie and Xinjian Yan, Encyclopedia of traditional Chinese Medicines, Molecular Structures, Pharmacological Activities, Natural Sources and Applications, Vol. 1–Vol. 6, Springer, Heidelberg Dordrecht London New York, 2011 R33 Jiaju Zhou, Guirong Xie and Xinjian Yan, TCM Series of Active Components, 10 books, Science Press, Beijing, 2012 (in Chinese)

How to Use the HAMNP Books In essence, from data computerization point of view, scientific knowledge is the expression of interrelation between research objects in different types. During a long coastline without computer, people learn and spread scientific knowledge in traditional ways, including education, reading, and exchanging information with each other. In today’s world, using computer’s powerful functions, we have a new way to learn systematical, complete knowledge. In short, a study process in the new way is to search and learn some relationships. Next, we discuss concretely how to use the HAMNP books. In these books, there are three kinds of data and three pairs of important relations. Three kinds of data are: (1) marine living sources (source); (2) secondary metabolites (compounds); and (3) pharmacological activities (pharm-activity). The three pairs of important relations are: (1) relationship between source and compounds; (2) relationship between compounds and pharm-activity; and (3) relationship between source and pharm-activity. In the case of asking questions, each relation has two directions; hence, together there are six types of questions: Type 1: from known source to unknown compound Type 2: from known compound to unknown source Type 3: from known compound to unknown pharm-activity Type 4: from known pharm-activity to unknown compound Type 5: from known source to unknown pharm-activity Type 6: from known pharm-activity to unknown source (Figure 1)

Source(s) Type 1

Type 5

Type 2

Type 6

Compound(s)

Type 4

Pharm-activity

Type 3

Figure 1: Kinds of Data and Six Types of Questions.

(1) An Illustration of Type 1 (and Type 3, Type 5) Question Up to now, what monoterpenoids and sesquiterpenoids are isolated from sea hares of genus Aplysia ? From index 3 of volume 1, one will get the following related data in detail: https://doi.org/10.1515/9783110655131-204

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How to Use the HAMNP Books

Aplysia angasi 77. Aplysia brasiliana 142, 145. Aplysia californica 20, 22, 23, 260. Aplysia dactylomela 15, 37, 46, 87, 88, 96, 124, 125, 128, 129, 130, 131, 261, 263, 265, 266, 267, 268, 273, 274, 328, 487, 488, 489, 491, 492. Aplysia kurodai 9, 10, 11, 12, 36, 171, 177, 178, 179, 180, 181. Aplysia punctata 5, 6, 7, 39, 46. Aplysia sp. 133. Aplysia spp. 129. Since compounds 1–50 are monoterpenoids, compounds 51–350 are sesquiterpenoids, and compounds 351–1131 are diterpenoids; thus, the answer of the current question must be: Aplysia angasi 77. Aplysia brasiliana 142, 145. Aplysia californica 20, 22, 23, 260. Aplysia dactylomela 15, 37, 46, 87, 88, 96, 124, 125, 128, 129, 130, 131, 261, 263, 265, 266, 267, 268, 273, 274, 328. Aplysia kurodai 9, 10, 11, 12, 36, 171, 177, 178, 179, 180, 181. Aplysia punctata 5, 6, 7, 39, 46. Aplysia sp. 133. Aplysia spp. 129. Then, readers can enjoy studying these 45 compounds by reading the book, including their pharm-activity (question of types 3 and 5). For example, with entry 21, a reader will know that compound 21 “8-Bromo-1,3,4,7-tetrachloro-3,7-dimethyl-1,5octadiene” had already been isolated from red algae Plocamium spp. in Antarctic, and they have antifungal pharmaceutical activity: Cl

Cl

Cl

Br

Cl

(2) An Illustration of Type 4 (and Type 2, Type 6) Question “What are isolated compounds with pharmacological activity against hmn nonsmall cell lung cancer from monoterpenoids and sesquiterpenoids? And what are their marine sources?” Because involving cancer cells, the List of Cancer Cell Codes must be used first. By the question, three related items were being collected as objects (small cell lung cancer):

How to Use the HAMNP Books

XXI

A549 hmn nonsmall cell lung cancer (cell) A549 NSCL hmn nonsmall cell lung cancer (cell) A549/ATCC hmn nonsmall cell lung cancer (cell) Then, to browse Index 5 of volume 1, searching “Cytotoxic, A549,” “Cytotoxic, A549 NSCL,” and “Cytotoxic, A549/ATCC,” respectively, the following results were obtained: Cytotoxic, A549 5, 6, 7, 51, 63, 64, 66, 78, 104, 105, 106, 107, 108, 164, 165, 167, 168, 218, 257, 271, 298, 319, 344, 345, 346, 347, 348, (352, 434, 435, 547, 548, 559, 561, 574, 575, 654, 655, 656, 657, 659, 673, 674, 675, 677, 678, 696, 712, 725, 726, 800, 841, 847, 873, 875, 906, 970, 1017, 1019, 1020, 1024, 1025, 1026, 1028, 1059, 1060, 1061, 1067, 1068, 1069, 1070, 1071, 1072, 1073, 1074, 1100, and 1101 are diterpenoids). Cytotoxic, A549 NSCL (435 is a diterpenoid). Cytotoxic, A549/ATCC (no entry in volume 1). Further, from the entry bodies of the 27 compounds (5, 6, 7,. . ., 346, 347, and 348), all sources can be obtained (see Table 2). In summary, by using three parts of the books – the contexts ordered by structural classifications, the text 8,350 compound entries in volumes 1–8, and the indexes – Table 2: Answer to the Above Type 6 Question. Vol.

Code

Compound Name

Related Sources





(Z,E)--Acetoxy--bromo-,-dichloro -,-dimethylocta-,-diene

Sea hare Aplysia punctata (Cádiz, Spain)





(E)--Acetoxy--chloro --(dichloromethyl)--methyloct--en-one

Sea hare Aplysia punctata (Cádiz, Spain)





(Z)--Acetoxy--chloro --(dichloromethyl)--methyloct--en-one

Sea hare Aplysia punctata (Cádiz, Spain)

. . .. . .

. . .. . .

. . .. . .

. . .. . .





Suberosenol A acetate

Gorgonian Isis hippuris





Suberosenol B

Gorgonian Isis hippuris





Suberosenol B acetate

Gorgonian Isis hippuris

readers can easily gain well-formatted systematically related knowledge in multidisciplinary fields.

List of Abbreviations and Acronyms [3H]AMPA [3H]CGS-19755 [3H]CPDPX [3H]DPDPE [3H]KA ‡ 3Y1 5-FU 6-MP 6-OHDA AAI ABRCA ABTS•+ ACAT ACE AChE ACTH ADAM9 ADAM10 ADM AGE AIDS AKT AKT1 ALK AMPB AP-1 APOBEC3G aq ARCA ARK5 ATCC ATPase Aurora-B AXL AZT BACE BACE1 BCG Bcl-2 BoMC BoMCL bp c CaMKIII cAMP CAPE

[3H]-1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid N-methyl-D-aspartic acid (NMDA) receptor antagonist [3H]-1,3-dipropyl-8-cyclopentylxanthine opioid peptide [3H]-kainic acid homonym mark rat fibroblasts 5-fluorouracil 6-mercaptopurine 6-hydroxydopamine antioxidant activity index (final DPPH concentration/EC50) amphotericin B-resistant Candida albicans 2,2′-azino-bis-(3-ethyl benzthiazoline 6-sulfonic acid), radical Acyl-CoA: cholesterol acyl transferase angiotensin-converting enzyme acetylcholinesterase adrenocorticotropic hormone ADAM9 protease ADAM10 protease adriamycin advanced glycation end products acquired immune deficiency syndrome ribosomal protein protein kinase protein kinase amphotericin B transcription factor hmn innate intracellular antiviral factor (recombinant protein) aqueous solution amphotericin-resistant Candida albicans protein kinase American Type Culture Collection adenosine triphosphatase protein kinase protein kinase 3′-azido-3′-deoxythymidine β-secretase β-secretase Bacille Calmette-Guérin a cell survival promoting factor further abbreviation on Bioorg. Med. Chem. further abbreviation on Bioorg. Med. Chem. Lett. boiling point concentration protein kinase cyclic adenosine monophosphate caffeic acid phenethyl ester

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List of Abbreviations and Acronyms

caspase-3 CB CC50 CCR5 CD Cdc2 Cdc25 Cdc25a Cdc25b CDDP CDK CDK1 CDK2 CDK4 CDK4/cyclin D1 P25 p25 CDK7 c-erbB-2 CETP cGMP CGRP ChAT CMV CNS COMPARE ConA COX-1 COX-2 CPB cPLA2 CPT CRPF CRPF FcM29 CSPF Cyp1A CYP1A CYP450 1A d D Delta DGAT DHFR DMSO DNA DOX DPI DPPH

caspase-3 protein cytochalasin B IC50 of cytotoxicity (concentration of the 50% cytotoxic effect) chemokine receptor 5 concentration required to double the specific activity cyclin-dependent kinase protein Cdc25 phosphatase protein phosphatase recombinant hmn phosphatase cis-diaminedichloroplatinum (cisplatin) cyclin-dependent kinase protein kinase protein kinase protein kinase cyclin-dependent kinase 4 (CDK4) in complex with its activator cyclin D1 protein kinase protein kinase protein kinase protein kinase cholesteryl ester transfer protein cyclic guanylic acid, cyclic guanosine monophosphate calcitonin gene-related peptide choline acetyltransferase CMV protease central nervous system COMPARE is an algorithm to analyze data concanavalin A cyclooxygenase-1 cyclooxygenase-2 further abbreviation on Chem. Pharm. Bull. cytosolic 85-kDa phospholipase camptothecin chloroquine-resistant Plasmodium falciparum chloroquine-resistant Plasmodium falciparum FcM29 chloroquine-sensitive Plasmodium falciparum aromatase cytochrome P450 1A cytochrome P450 1A cytochrome P450 1A day diameter (mm) difference in log10 GI50 (mol/L) value of the most sensitive cell line and MGMID value diacylglycerol acyltransferase dihydrofolate reductase dimethyl sulfoxide deoxyribonucleic acid doxorubicin diphenylene indonium 1,1-diphenyl-2-picrylhydrazyl free radical

List of Abbreviations and Acronyms

DRPF DRS DSPF DYRK1A EBV EC EC50 ED50 ED50 EGF EGFR EL-4 ELISA EPI ERK ESBLs EurJOC FAK FBS FLT3 Flu-A Flu-B fMLP/CB FOXO1a fp FPT FRCA FtsZ FXR GABA GI50 GlyR gp41 gpg GPR12 GRP78 GST GTP GU4 GU5 h H1N1 H3N2 H5N1 HBV HC50 HCMV

XXV

drug-resistant Plasmodium falciparum drug-resistant Staphylococcus sp. drug-sensitive Plasmodium falciparum protein kinase Epstein–Barr virus effective concentration medium effective concentration effective dose for 50% medium effective dose (sometimes for the medium effective concentration) epidermal growth factor epidermal growth factor receptor lymphoma cell line with resistance to natural killer cells enzyme-linked immunosorbent assay epirubicin extracellular signal-regulated protein kinase extended spectrum β-lactamase further abbreviation on Eur. J. Org. Chem. protein kinase fetal bovine serum a protein tyrosine kinase influenza virus type A influenza virus type B N-formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B downstream target of PTEN tumor suppressor freezing point Farnesyl protein transferase fluconazole-resistant Candida albicans A structural homolog of eukaryotic tubulin, a GTPase farnesoid X receptor γ-aminobutyric acid the concentration of sample necessary to inhibit the growth to 50% of the control glycine-gated chloride channel receptor a transmembrane protein of HIV-1 (recombinant protein) guinea pig G protein-coupled receptor 12; it can be a significant molecular target for treating a variety of neurological disorders molecular chaperone (chaperone) glutathione S-transferases guanosine triphosphate Candida albicans-sensitive GU4 strain Candida albicans-resistant GU5 strain hour influenza virus H1N1 influenza virus H3N2 influenza virus A H5N1 hepatitis B virus medium hemolytic concentration hmn cytomegalovirus

XXVI

HCV HD HER2 HF HIF-1 HIV HIV-1 HIV-1 IIIB HIV-1 in HIV-1 RF HIV-1-rt HIV-2 HIV-rt HLE HMG-CoA hmn HNE HO• hPPARd HSV HSV-1 HSV-2 hTopo l HXB2 IC IC50 IC90 IC100 ICR ID ID50 IDE IDO IFV IgE IGF1-R IgM IL IL-1 IL-1α IL-1β IL-2 IL-4 IL-5 IL-6 IL-8 IL-12 IL-13

List of Abbreviations and Acronyms

hepatitis C virus a positive control compound, no concrete explanation in original paper (J. Qin, et al., BoMCL, 2010, 20, 7152) tyrosine kinase hypersensitivity factor hypoxia-inducible factor-1 hmn immunodeficiency virus hmn immunodeficiency virus type 1 hmn immunodeficiency virus type 1 IIIB hmn immunodeficiency virus type 1 integrase hmn immunodeficiency virus RF hmn immunodeficiency virus type 1 reverse transcriptase hmn immunodeficiency virus type 2 hmn immunodeficiency virus reverse transcriptase hmn leukocyte elastase 3-hydroxy-3-methylglutaryl coenzyme A reductase human hmn neutrophil elastase hydroxyl radical hmn peroxisome proliferator-activated receptor delta herpes simplex virus herpes simplex virus 1 herpes simplex virus 2 hTopo l isomerase T-cell tropic viral strain inhibiting concentration median inhibiting concentration inhibiting concentration for 90% absolute inhibiting concentration imprimting control region mouse inhibition diameter (mm) median inhibiting dose insulin-degrading enzyme indoleamine 2,3-dioxygenase influenza virus immunoglobulin E protein kinase immunoglobulin M interleukin interleukin-1 interleukin-1α interleukin-1β interleukin-2 interleukin-4 interleukin-5 interleukin-6 interleukin-8 interleukin-12 interleukin-13

List of Abbreviations and Acronyms

IM IMPDH IN iNOS InRt ip iv IZ IZD IZR JACS Jak2 JCS Perkin I JMC JNK JNP JOC KDR KU-812 LAV LC50 LCV LD LD100 LD50 LD99 LDH LOX LPS LTB4 LTC4 LY294002 MABA MAGI test MAPKAPK-2 MAPKK MBC MBC90 MBEC90 MCV MDR MDR1 MDRPF MDRSA MDRSP MEK1 wt MET wt

XXVII

immunomodulator inosine monophosphate dihydrogenase integrase inducible nitric oxide synthase inhibitive rate intraperitoneal injection intravenous injection inhibition zone (mm) inhibition zone diameter (mm) inhibition zone radii (mm) further abbreviation on J. Am. Chem. Soc. Janus kinase 2 further abbreviation on J. Chem. Soc., Perkin Trans. I further abbreviation on J. Med. Chem. c-Jun NH2-terminal kinase further abbreviation on J. Nat. Prod. further abbreviation on J. Org. Chem. a protein tyrosine kinase hmn basophilic granulocyte T-cell tropic viral strain concentration at which only 50% of the cells are viable lymphocyte viability lethal dose 100% lethal dose medium lethal dose 99% lethal dose lactate dehydrogenase lipoxygenase lipopolysaccharide leukotriene B4 leukotriene C4 phosphatidylinositol-3-kinase inhibitor, using as a positive control in anti-inflammatory assay microplate alamar blue assay also called single life cycle test, reflects only one round of infection mitogen-activated protein kinase-activated protein kinase 2 mitogen-activated protein kinase kinase minimum bactericidal concentration minimum bactericidal concentration for 90% minimum biofilm eradication counts for 90% poxvirus Molluscum contagiosum virus multidrug resistance major facilitator superfamily 1; one type of efflux pump in C. albicans, which functions as an H+-antiporter multidrug-resistant Plasmodium falciparum multidrug-resistant Staphylococcus aureus multidrug-resistant Streptococcus pneumonia protein kinase protein kinase

XXVIII

MG-MID MIA MIC MIC50 MIC80 MIC90 MID min MLD MLR MMOA MMP MMP-2 MoBY-ORF mp MPtpA MPtpB mPTPB MREC MRSA MRSE MSR MSSA MSSE MT1-MMP MT4 MTT MTT assay mus n nACh NADH NDM-1 NEK2 NEK6 NF-κB

NFRD NGF NMDA NO• NPR O2•− ONOO− ORAC orl p24

List of Abbreviations and Acronyms

mean value of log10 GI50 (mol/L) over all cell lines tested minimal inhibitory amounts (μg/disk) minimum Inhibitory concentration minimal Inhibitive concentration for 50% minimal Inhibitive concentration for 80% minimal inhibitive concentration for 90% minimum inhibitory dose minute minimum lethal dose mixed lymphocyte reaction molecular mechanism of action matrix metalloproteinases matrix metalloproteinase-2 molecular barcoded yeast open-reading frame library method melting point mycobacterial protein tyrosine phosphatase A mycobacterial protein tyrosine phosphatase B Mycobacterium tuberculosis protein tyrosine phosphatase B methicillin-resistant Escherichia coli methicillin-resistant Staphylococcus aureus methicillin-resistant Staphylococcus epidermidis macrophage scavenger receptor methicillin-sensitive Staphylococcus aureus methicillin-sensitive Staphylococcus epidermidis membrane-type 1 matrix metalloproteinase MT4 cells containing HIV-1 IIIB virus 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide A cytotoxicity measurement method, tetrazolium-based colorimetric assay; see L. V. Rubinstein, et al., Nat. Cancer Inst., 82, 1113–1118 (1990) mouse number of parallel experiments nicotinic acetylcholine reduced nicotinamide adenine dinucleotide New Delhi metallo-β-lactamase-1 protein kinase protein kinase NF-κB serves as a central regulator of hmn immune, inflammatory, and antiapoptotic responses (Ghosh et al., 1998, Ann. Rev. Immunol, 16, 225-260) NADH-fumarate reductase nerve growth factor N-methyl-D-aspartate nitric oxide free radical further abbreviation on Nat. Prod. Rep. superoxide free radical peroxy nitrite free radical oxygen radical absorbance capacity oral p24 protein

List of Abbreviations and Acronyms

P2Y receptors P2Y11 receptor P450 p56lck PAcF PAF PD pD2 (=pEC50) PDE5 PDGF PfGSK-3 Pfnek-1 PfPK5 PfPK7 PGE2 PHK PIM1 PK PKA PKC PKC-ε PKD PKG PLA PLA2 PLCγ1 PLK1 PM PMA (=TPA) PMNL PP PP1 PP2A pp60V-SRC PPAR PPDK PR PRK1 PRNG PRSP PTEN PTK PTP1B PTPB PTPS2

XXIX

one type of purine receptors which includes P1 (adenosine receptors) and P2 receptors [ionotropic P2X and metabotropic (G protein-coupled) P2Y] one of eight P2Y subtypes cytochrome P450 tyrosine kinase platelet activating factor platelet aggregation factor Parkinson’s disease negative logarithm (−log M) of molar concentration required to produce 50% of the maximum response (EC50) phosphodiesterase 5 platelet-derived growth factor kinase a NIMA-related protein kinase of Plasmodium falciparum kinase kinase prostaglandin E2 primary hmn keratinocytes protein kinase protein kinase protein kinase A protein kinase C protein kinase C-ε ribosomal protein protein kinase G phospholipase A phospholipase A2 ribosomal protein protein kinase further abbreviation on Planta Med. phorbol-12-myristate-13-acetate hmn polymorphonuclear leukocyte protein phosphatase protein phosphatase PP1 protein phosphatase PP2A tyrosine kinase peroxisome proliferator-activated receptor pyruvate phosphate dikinase protease protein kinase penicillin-resistant Neisseria gonorrhoeae penicillin-resistant Staphylococcus pneumoniae tumor suppressor, an identified tumor suppressor gene located on hmn chromosome 10q23.3 protein tyrosine kinase protein tyrosine phosphatase 1B, an important target for treatment of type II diabetes protein tyrosine phosphatase B protein tyrosine phosphatase S2

XXX

List of Abbreviations and Acronyms

PV-1 PXR QR Range rat rbt RLAR RNA ROS RS321 RSV RT RU RyR1-FKBP12 S6 SAK SARS ScRt SF162 SI SI SI SI SI SIRT2

sp. spp. SR SRB SRC SV40 Syn. T/C TACE Taq DNA polymerase TBARS TC50 TEAC TGI TMV TNFα TPA (=PMA)

Polio virus pregnane X receptor NAD(P)H: quinone reductase difference in log10 GI50 (mol/L) value of the most sensitive cell line and the least sensitive cell white rat rabbit rat lens aldose reductase ribonucleic acid reactive oxygen species (involved in genesis of various cancers, arteriosclerosis, rheumatism, and aging) code of a yeast respiratory syncytial virus reverse transcriptase response unit of binding capacity to HIV-1 targets, 1 RU = 1 pg/mm2 RyR1-FKBP12 Ca2+ channel, a tetrameric heterodimeric channel protein (~2000 kDa) associated with smaller 12 kDa immunophilin FKBP12 ribosomal protein a protein kinase severe acute respiratory syndrome scavenging rate macrophage-tropic viral strain IC50 of testing cells/IC50 of HUVECs selective index = cytotoxic CC50/target EC50 selective index = cytotoxic IC50/target IC50 selective index = cytotoxic IC50/target MIC selective index = cytotoxic TC50/target IC50 hmn sirtuin type 2 (a NAD+-dependent cytoplasmic protein that is colocalized with HDAC6 on microtubules. SIRT2 has been shown to deacetylate α-tubulin and to control mitotic exit from the cell cycle) species species (plural) sarcoplasmic reticulum sulforhodamine B assay protein kinase SV40 virus synonym survival ratio [survival time of treated animal (T) was compared to that of control animal (C) expressed as a percent (T/C%)] ɑ-secretase (a serine protease) a DNA polymerase isolated from the thermophilic bacterium Thermus aquaticus thiobarbituric acid-reactive substance assay 50% cytotoxic concentration Trolox equivalent antioxidant capacity 100% growth inhibition tobacco mosaic virus tumor necrosis factor-α 12-O-tetradecanoyl phorbol 13-acetate

List of Abbreviations and Acronyms

TPK TRP TRPA1 TRPV1 TRPV3 TXB2 TZM-bl USP7 VCAM VCAM-1 VCR VEGF VEGF-A VEGFR2 VE-PTP VGSC VHR Vif VP-16 VRE VREF VSE VSSC VSV WST-8 XTT YU2-V3

XXXI

tyrosine protein kinase transient receptor potential cationic channel transient receptor potential cationic channel of subfamily A1 transient receptor potential cationic channel of subfamily V1 transient receptor potential cationic channel of subfamily V3 thromboxane B2 host cell in HIV-1 neutralization assay a deubiquitylating enzyme hydrolyzing isopeptide bond at C-terminus of ubiquitin, is an emerging cancer target vascular cell adhesion molecule vascular cell adhesion molecule-1 vincristine vascular endothelial growth factor vascular endothelial growth factor A tyrosine kinase VEGFR2 protein phosphatase voltage-gated sodium channel vaccinia open-reading frame H1-related protein phosphatase viral infectivity factor of HIV-1 etoposide (Sigma product), a positive control for cytotoxic assay vancomycin-resistant Enterococcus sp. vancomycin-resistant Enterococcus faecium vancomycin-sensitive Enterococcus sp. voltage-sensitive sodium channel Vesicular stomatitis virus 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfo-phenyl)2H-tetrazolium, monosodium salt sodium 3′-[1-(phenylaminocarbonyl)-3,4-tetrazolium] bis(4-methoxy-6nitrobenzene)sulfonic acid viral strain

List of Cancer Cell Codes This set of codes for 438 cancer cells, named as CCC codes, are defined and tried out in the books by the author. The codes of some normal cells are included in this list also. 293T 3T3-L1 5637 786-0 9KB A-10 A2058 A278 A2780 A2780CisR A2780/DDP A2780/Tax A375 A375-S2 A431 A498 A549 A549 NSCL A549/ATCC ACC-MESO-1 ACHN AGS AsPC-1 B16 B16F1 B16-F-10 BC BC-1 BCA-1 BEAS2B Bel7402 BG02 BGC823 BOWES BR1 BSC BSC-1 BSY1 BT-483 BT549 BT-549 BXF-1218L BXF-T24 BXPC

kidney epithelial cells murine fibroblasts superficial bladder cancer (cell) hmn renal cancer (cell) hmn epidermatoid nasopharyngeal carcinoma (cell) rat aorta cells hmn (cell) hmn ovarian tumor (cell) hmn ovarian tumor (cell) hmn ovarian tumor (cell) hmn ovarian tumor (cell) hmn ovarian tumor (cell) hmn melanoma (cell) hmn melanoma (cell) hmn epidermic cancer (cell) hmn renal cancer (cell) hmn nonsmall cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn malignant pleural mesothelioma (cell) hmn renal cancer (cell) gastric adenocarcinoma (cell) hmn pancreatic cancer (cell) mouse melanoma (cell) mouse melanoma (cell) mouse melanoma (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) normal hmn lung bronchial cells hmn liver cancer (cell) normal hmn embryonic stem cells hmn gastric cancer (cell) hmn cells DNA repair competent Chinese hamster ovary (cell) normal monkey kidney cells normal African Green Monkey kidney cells breast cancer (cell) hmn breast carcinoma (cell) hmn galactophore cancer (cell) hmn breast cancer (cell) hmn bladder cancer (cell) hmn bladder cancer (cell) hmn pancreas cancer (cell)

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XXXIV

BXPC3 C6 C26 C38 CA46 Ca9-22 CaCo-2 CAKI-1 Calu Calu3 CCRF-CEM CCRF-CEMT CEM CEM-TART CFU-GM CHO CHO-K1 CML K562 CNE CNE2 CNS SF295 CNXF-498NL CNXF-SF268 Colo320 Colo357 Colon26 Colon38 Colon205 Colon250 CV-1 CXF-HCT116 CXF-HT29 DAMB DG-75 DLAT DLD-1 DLDH DMS114 DMS273 Doay Dox40 DU145 DU4475 E39 EAC EKVX EM9 EMT-6 EPC

List of Cancer Cell Codes

hmn pancreas cancer (cell) rat glioma (cell) hmn colon carcinoma (cell) murine colon adenocarcinoma (cell) hmn Burkitt lymphoma (cell) hmn gingival carcinoma (cell) hmn epithelial colorectal adenocarcinoma (cell) hmn renal cancer (cell) prostate carcinoma (cell) nonsmall cell lung cancer (cell) hmn T-cell acute lymphoblastic leukemia (cell) leukemia (cell) hmn leukemia (cell) T-cells that express both HIV-1 tat and rev hmn/murine hematopoietic progenitor cells Chinese hamster ovary cells subclone of normal Chinese hamster ovary cells chronic myelogenous leukemia (cell) hmn nasopharyngeal carcinoma (cell) hmn nasopharyngeal carcinoma (cell) hmn brain tumor (cell) hmn glioblastoma cancer (cell) hmn glioblastoma cancer (cell) hmn colorectal cancer (cell) hmn colorectal cancer (cell) colorectal cancer (cell) mus colorectal cancer (cell) colorectal cancer (cell) colorectal cancer (cell) monkey kidney fibroblasts hmn colon cancer (cell) hmn colon cancer (cell) hmn mammary carcinoma (cell) hmn B lymphocyte (cell) Dalton’s lymphoma ascites tumor (cell) hmn colorectal adenocarcinoma (cell) hmn colorectal adenocarcinoma (cell) hmn lung cancer (cell) hmn small cell lung cancer (cell) hmn medulloblastoma (cell) hmn myeloma (cell) prostate cancer (cell) breast cancer (cell) hmn renal carcinoma (cell) Ehrlich ascites carcinoma (cell) hmn nonsmall cell lung cancer (cell) topoisomerase I-sensitive Chinese hamster ovary (cell) mouse tumor cells carp epithelium (cell)

List of Cancer Cell Codes

EVLC-2 F1 FADU Farage Fem-X Fl FM3C G402 GM7373 GR-III GXF-251L H116 H125 H441 H460 H522 H1299 H1325 H1975 H2122 H2887 H69AR H929 H9c2 HBC4 HBC5 HBL100 HCC366 HCC2998 HCC-S102 HCT HCT8 HCT15 HCT29 HCT116 HCT116/mdr+ HCT116/topo HCT116/VM46 HEK-293 HEL HeLa HeLa-APL HeLa-S3 Hep2 Hep3B HepA Hepa1c1c7 HepG HepG2

SV40 large T-antigen immortalized hmn umbilical vein cells hmn amniotic epithelial cells pharynx-sq cancer (cell) hmn lymphoma (cell) melanoma (cell) hmn amniotic epithelial cell line mus mammary tumor (cell) hmn renal leiomyoblastoma bovine endothelial (cell) adenocarcinoma (cell) hmn stomach cancer (cell) hmn colorectal cancer (cell) hmn colorectal cancer (cell) hmn lung adenocarcinoma (cell) hmn lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn lung adenocarcinoma (cell) hmn nonsmall cell lung cancer (cell) hmn cancer (cell) hmn nonsmall cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) multidrug-resistant small cell lung cancer (cell) hmn myeloma (cell) rat cardiac myoblasts breast cancer (cell) breast cancer (cell) breast cancer (cell) hmn nonsmall cell lung cancer (cell) hmn colorectal cancer (cell) hepatocellular carcinoma (cell) hmn colorectal cancer (cell) hmn colorectal cancer (cell) hmn colorectal cancer (cell) hmn colon adenocarcinoma (cell) hmn colorectal cancer (cell) overexpress mdr+ hmn colorectal cancer (cell) resistant to etoposide hmn colorectal cancer (cell) multidrug-resistant colorectal cancer (cell) normal hmn epithelial kidney cells hmn embryonic lung fibrocytes hmn cervical epithelial carcinoma (cell) hmn cervical epithelial cancer (cell) hmn cervical epithelial cancer (cell) hmn liver carcinoma (cell) hmn liver cancer (cell) hmn liver cancer ascites (cell) mus liver cancer (cell) hmn liver cancer (cell) hmn liver cancer (cell)

XXXV

XXXVI

HepG3 HepG3B HEY HFF HL60 HL7702 HLF HM02 HMEC HMEC1 HNXF-536L HOP-18 HOP-62 HOP-92 Hs578T Hs683 HSV-1 HT HT29 HL60 HT115 HT460 HT1080 HTC116 HTCLs HuCCA-1 Huh7 HUVEC HUVECs IC-2WT IGR-1 IGROV IGROV1 IGROV-ET IMR-32 IMR-90 J774 J774.1 J774.A1 JB6 CI41 JB6 P+CI41 JurKat JurKat-T K462 K562 KB KB16 KB-3 KB-3-1

List of Cancer Cell Codes

hmn liver cancer (cell) hmn liver cancer (cell) hmn ovarian carcinoma (cell) hmn foreskin fibroblasts hmn promyelocytic leukemia (cell) hmn liver tumor (cell) hmn lung fibroblasts hmn gastric adenocarcinoma (cell) hmn microvascular endothelial cells hmn microvascular endothelial cells hmn head and neck cancer (cell) hmn nonsmall cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn breast cancer (cell) hmn oligodendroglioma (black dots) (cell) nonmalignant cell hmn lymphoma (cell) hmn colorectal cancer (cell) M. Daferner, et al., Z. Naturforsch., Teil C, 1999, 54, 474 hmn colorectal cancer (cell) hmn tumor (cell) hmn fibrosarcoma (cell) hmn acute promyelocytic leukemia (cell) hmn tumors (cells) hmn cholangiocarcinoma cancer (cell) hmn hepatoma (cell) hmn umbilical vein endothelial cell hmn umbilical vein endothelial cell murine cell line hmn melanoma (cell) hmn ovarian cancer (cell) hmn ovarian cancer (cell) hmn ovarian cancer (cell) hmn neuroblastoma (cell) hmn diploid lung fibroblasts mus monocyte/macrophage (cell) mus monocyte/macrophage (cell) mus monocyte/macrophage (cell) mouse epidermal cells mouse epidermal cells hmn leukemia (cell) hmn T-cell leukemia (cell) hmn leukemia (cell) hmn chronic myelogenous leukemia (cell) hmn nasopharyngeal carcinoma (cell) hmn nasopharyngeal carcinoma (cell) hmn epidermoid carcinoma (cell) hmn epidermoid carcinoma (cell)

List of Cancer Cell Codes

KB-C2 KB-CV60 KBV200 Ketr3 KM12 KM20L2 KMS34 KU812F KV/MDR KYSE30 KYSE70 KYSE180 KYSE520 L1210 L1210/Dx L363 L-428 L5178 L5178Y L-6 L929 LLC-PK1 LMM3 LNCaP LO2 LoVo LoVo-DOX LOX LOX-IMVI LX-1 LXF-1121L LXF-289L LXF-526L LXF-529L LXF-629L LXFA-629L LXF-H460 M14 M16 M17 M17-Adr M21 M5076 MAGI MALME-3 MALME-3M MAXF-401 MAXF-401NL MAXF-MCF7

hmn carcinoma (cell) hmn carcinoma (cell) MDR nasopharyngeal carcinoma (cell) hmn renal cancer (cell) hmn colorectal cancer (cell) hmn colorectal cancer (cell) hmn myeloma (cell) hmn leukemia (cell) multidrug-resistant cancer (cell) hmn esophageal cancer (cell) hmn esophageal cancer (cell) hmn esophageal cancer (cell) hmn esophageal cancer (cell) mouse lymphocytic leukemia (cell) doxorubicin-resistant L1210 (cell) hmn myeloma (cell) leukemia (cell) mouse lymphosarcoma (cell) mouse lymphosarcoma (cell) rat skeletal myoblasts (cell) mouse fibroblasts pig kidney cells mouse mammary adenocarcinoma (cell) hmn prostate cancer (cell) hmn liver cells hmn colorectal cancer (cell) hmn colorectal cancer (cell) hmn melanoma (cell) hmn melanoma (cell) hmn lung cancer (cell) hmn lung cancer (cell) hmn lung cancer (cell) hmn lung cancer (cell) hmn lung cancer (cell) hmn lung cancer (cell) lung adenocarcinoma (cell) hmn lung cancer (cell) melanoma (cell) murine colon adenocarcinoma (cell) adriamycin-resistant breast cancer (cell) adriamycin-resistant breast cancer (cell) melanoma (cell) ovarian sarcoma (cell) Hela-CD4-LTR-β-gal (indicator) cells containing HIV-1 IIIB virus melanoma (cell) melanoma (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell)

XXXVII

XXXVIII

List of Cancer Cell Codes

MCF MCF-10A MCF7 MCF7 Adr MCF7/Adr MCF7/ADR-RES MCF12 MDA231 MDA361 MDA435 MDA468 MDA-MB MDA-MB-231 MDA-MB-231/ATCC MDA-MB-435 MDA-MB-435s MDA-MB-468 MDA-N MDCK ME180 MEL28 MES-SA MES-SA/DX5 MEXF-276L MEXF-394NL MEXF-462NL MEXF-514L MEXF-520L MG63 MGC-803 MiaPaCa Mia-PaCa-2 MKN1 MKN7 MKN28 MKN45 MKN74 MM1S Molt3 Molt4 Mono-Mac-6 MPM ACC-MESO-1 MRC-5 MRC5CV1 MS-1 MX-1 N18-RE-105 N18-T62 NAMALWA

hmn breast cancer (cell) hmn breast epithelial (cell) hmn breast cancer (cell) drug-resistant hmn breast MCF7 cancer (cell) drug-resistant hmn breast MCF7 cancer (cell) drug-resistant hmn breast cancer MCF7 (cell) hmn esophageal cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) Madin–Darby Canine (cell) cervical cancer (cell) hmn melanoma (cell) hmn uterine (cell) hmn uterine (cell) hmn melanoma (cell) hmn melanoma (cell) hmn melanoma (cell) hmn melanoma (cell) hmn melanoma (cell) hmn osteosarcoma (cell) hmn cancer (cell) hmn pancreas cancer (cell) hmn pancreas cancer (cell) hmn gastric cancer (cell) hmn gastric cancer (cell) hmn gastric cancer (cell) hmn gastric cancer (cell) hmn gastric cancer (cell) hmn myeloma (cell) leukemia (cell) hmn T lymphocyte leukemia (cell) mononuclear cells hmn malignant pleural mesothelioma normal hmn diploid embryonic cells SV40-transformed hmn fibroblasts mice endothelial cells hmn mammary carcinoma xenografts neuronal hybridoma (cell) mus neuroblastoma (cell) leukemia (cell)

List of Cancer Cell Codes

NBT-T2 (BRC-1370) NCI-ADR NCI-ADR-Res NCI-H23 NCI-H69 NCI-H82 NCI-H187 NCI-H226 NCI-H322M NCI-H446 NCI-H460 NCI-H510 NCI-H522 neuro-2a NFF NHDF NIH3T3 NIH3T3 NMuMG NOMO-1 NS-1 NSCLC NSCLC HOP-92 NSCLC-L16 NSCLC-N6 NSCLC-N6-L16 NUGC-3 OCILY17R OCIMY5 OPM2 OVCAR-3 OVCAR-4 OVCAR-5 OVCAR-8 OVXF-1619L OVXF-899L OVXF-OVCAR3 P388 P388/ADR P388/Dox P388D1 PANC1 panc89 PAXF-1657L PAXF-PANC1 PBMC PC12 PC-12 PC3

rat bladder epithelial cells hmn ovarian sarcoma (cell) hmn ovarian sarcoma (cell) hmn nonsmall cell lung cancer (cell) hmn lung cancer (cell) hmn lung cancer (cell) hmn small cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn lung cancer (cell) hmn nonsmall cell lung cancer (cell) mouse neuroblastoma (cell) nonmalignant neonatal foreskin fibroblasts normal hmn dermal fibroblasts nontransformed fibroblasts normal fibroblasts nontransformed epithelial cells hmn acute myeloid leukemia murine cells hmn bronchopulmonary nonsmall cell lung cancer hmn nonsmall cell lung cancer (cell) hmn bronchopulmonary nonsmall cell lung carcinoma hmn bronchopulmonary nonsmall cell lung cancer (cell) hmn bronchopulmonary nonsmall cell lung carcinoma hmn gastric cancer (cell) hmn lymphoma (cell) hmn myeloma (cell) hmn myeloma (cell) ovarian adenocarcinoma (cell) ovarian adenocarcinoma (cell) ovarian adenocarcinoma (cell) ovarian adenocarcinoma (cell) ovary cancer (cell) ovary cancer (cell) ovary cancer (cell) mus lymphocytic leukemia (cell) P388 adriamycin-resistant (cell) mus leukemia cells expressing resistance toward doxorubicin mus macrophage cells hmn pancreas cancer (cell) pancreatic cancer (cell) hmn pancreas cancer (cell) hmn pancreas cancer (cell) hmn normal peripheral blood mononuclear cells hmn lung cancer (cell) rat pheochromocytoma (cell) hmn prostate cancer (cell)

XXXIX

XL

List of Cancer Cell Codes

PC3M PC3MM2 PC-9 PRXF-22RV1 PRXF-DU145 PRXF-LNCAP PRXF-PC3M PS (=P388) PV1 PXF-1752L QG56 QGY-7701 QGY-7703 Raji RAW264.7 RB RBL-2H3 RF-24 RKO RKO-E6 RPMI7951 RPMI8226 RXF-1781L RXF-393 RXF-393NL RXF-486L RXF-631L RXF-944L S180 S180A SAS SCHABEL SF268 SF295 SF539 SGC7901 SH-SY5Y SK5-MEL SKBR3 SK-Hep1 SK-MEL-2 SK-MEL-5 SK-MEL-28 SK-MEL-S SK-N-SH SK-OV-3 SMMC-7721

hmn prostate cancer (cell) hmn prostate cancer (cell) hmn lung cancer (cell) hmn prostate cancer (cell) hmn prostate cancer (cell) hmn prostate cancer (cell) hmn prostate cancer (cell) PS system, P388 mouse lymphocytic leukemia (cell) nonmalignant cell mesothelioma cancer (cell) hmn lung carcinoma (cell) hmn hepatocellular carcinoma (cell) hmn liver cancer (cell) hmn EBV-transformed Burkitt’s lymphoma B cell mouse macrophages hmn prostate cancer (cell) rat basophilic cells papillomavirus 16 E6/E7 immortalized hmn umbilical vein cells hmn colon cancer (cell) hmn colon cancer (cell) hmn malignant melanoma (cell) hmn myeloma (cell) renal cancer (cell) renal cancer (cell) renal cancer (cell) renal cancer (cell) renal cancer (cell) renal cancer (cell) mouse sarcoma (cell) sarcoma 180 ascites cells hmn oral cancer mouse lymphoma cancer (cell) hmn brain tumor (cell) hmn brain tumor (cell) hmn brain tumor (cell) hmn gastric cancer (cell) hmn neuroblastoma (cell) hmn melanoma (cell) hmn breast cancer (cell) hmn liver carcinoma (cell) hmn melanoma (cell) hmn melanoma (cell) hmn melanoma (cell) hmn melanoma (cell) neuroblastoma (cell) ovarian adenocarcinoma (cell) hmn liver cancer (cell)

List of Cancer Cell Codes

SN12C SN12k1 SNB19 SNB75 SNB78 SNU-C4 SR St4 stromal cell SUP-B15 Sup-T1 SW480 SW620 SW1573 SW1736 SW1990 T24 T-24 T47D THP-1 TK10 tMDA-MB-231 tsFT210 TSU-Pr1 TSU-Pr1-B1 TSU-Pr1-B2 U251 U266 U2OS U373 U373MG U-87-MG U937 UACC-257 UACC62 UO-31 UT7 UV20 UXF-1138L V79 Vero WEHI-164 WHCO1 WHCO5 WHCO6 WI26 WiDr

hmn renal cancer (cell) hmn renal cancer (cell) hmn brain tumor (cell) hmn CNS cancer (cell) hmn brain tumor (cell) hmn cancer (cell) leukemia (cell) gastric cancer (cell) bone marrow stromal cells leukemia (cell) T-cell lymphoma cancer cells hmn colorectal adenocarcinoma (cell) hmn colorectal adenocarcinoma (cell) hmn nonsmall cell lung cancer (cell) hmn thyroid cancer (cell) hmn pancreatic cancer (cell) hmn liver cancer (cell) hmn transitional bladder carcinoma (cell) hmn breast cancer (cell) hmn acute monocytic leukemia (cell) hmn renal cancer (cell) hmn breast cancer (cell) mouse cancer (cell) invasive bladder cancer (cell) invasive bladder cancer (cell) invasive bladder cancer (cell) CNS tumor/glioma (cell) myeloma (cell) hmn osteosarcoma (cell) glioblastoma/astrocytoma (cell) hmn brain cancer (cell) caucasian glioblastoma (cell) hmn monocytic leukemia (cell) melanoma (cell) melanoma (cell) hmn renal cancer (cell) hmn leukemia (cell) DNA cross-linking agent sensitive Chinese hamster ovary (cell) hmn uterus cancer (cell) Chinese hamster (cell) green monkey kidney tumor (cell) mus fibrosarcoma (cell) hmn esophageal cancer (cell) hmn esophageal cancer (cell) hmn esophageal cancer (cell) hmn lung fibroblasts hmn colon adenocarcinoma (cell)

XLI

XLII

WMF XF498 XRS-6 XVS ZR-75-1

List of Cancer Cell Codes

hmn prostate cancer (cell) hmn CNS cancer (cell) topoisomerase II-sensitive Chinese hamster ovary (cell) topoisomerase II-sensitive CHO cell hmn breast cancer (cell)

1 Monoterpenoids 1.1 Acyclic Monoterpenoids 1 Citronellol 3,7-Dimethyl-6-octen-1-ol Type: Acyclic monoterpenoids. C10H20O Source: Bryozoan Flustra foliacea, and occurs in many essential oils. Pharm: LD50 (rat, orl) = 3450 mg/kg. LD50 (rbt, skn) = 2650 mg/kg. Ref: C. Christophersen, et al, Naturwissenschaften, 1978, 65, 440

OH

2 Geraniol Type: Acyclic monoterpenoids. C10H18O Oil with sweet rose odour, bp 230 °C. Source: Bryozoan Flustra foliacea. Pharm: Skin irritant; LD50 (rat, orl) = 3600 mg/kg. Ref: C. Christophersen, et al, Naturwissenschaften, 1978, 65, 440

OH

3 Isoplocamenone Type: Acyclic monoterpenoids. C10H12BrCl3O Unstable colorless to light brown oil. Source: Red alga Plocamium angustum (Pt. Lonsdale, Vic., Australia). Pharm: Cytotoxic (mixture with Plocamenone, P388, IC50 < 97.5 ng/mL). Ref: M. A. Timmers, et al, Mar. Drugs, 2012, 10, 2089 Cl

Cl Cl

O

Br

4 Plocamenone Type: Acyclic monoterpenoids. C10H12BrCl3O Stable colorless to light brown oil, [α]D = −21.5° (c = 4.58 mg/mL, CHCl3). Source: Red alga Plocamium angustum (Pt. Lonsdale, Vic., Australia). Pharm: Cytotoxic (P388, IC50 < 97.5 ng/mL). Ref: M. A. Timmers, et al, Mar. Drugs, 2012, 10, 2089

O Cl Cl

Cl Br

https://doi.org/10.1515/9783110655131-001

2

1 Monoterpenoids

1.2 Halogenated Dimethyloctane Monoterpenoids 5 (3Z,5E)-1-Acetoxy-8-bromo-4,7-dichloro-3,7-dimethylocta-3,5-diene Type: Halogenated dimethyloctane monoterpenoids. C12H17BrCl2O2 Colorless oil, [α]D25 = −4.8° (c = 0.2, CHCl3). Source: Sea hare Aplysia punctata (Cádiz, Spain). Pharm: Cytotoxic (P388, ED50 = 2.5 μg/mL, HT29, ED50 = 2.5 μg/mL, A549, ED50 = 1.5 μg/mL, MEL28, ED50 = 1.5 μg/mL). Ref: M. J. Ortega, et al, JNP, 1997, 60, 482 Br O Cl O Cl

6 (7E)-1-Acetoxy-8-chloro-7-(dichloromethyl)-3-methyloct-7-en-4-one Type: Halogenated dimethyloctane monoterpenoids. C12H17Cl3O3 Colorless oil, [α]D25 = −3.7° (c = 0.19, CHCl3). Source: Sea hare Aplysia punctata (Cádiz, Spain). Pharm: Cytotoxic (P388, ED50 = 2.5 μg/mL, HT29, ED50 = 2.5 μg/mL, A549, ED50 = 1.5 μg/mL, MEL28, ED50 = 1.5 μg/mL). Ref: M. J. Ortega, et al, JNP, 1997, 60, 482 Cl

Cl

O O

Cl

O

7 (7Z)-1-Acetoxy-8-chloro-7-(dichloromethyl)-3-methyloct-7-en-4-one Type: Halogenated dimethyloctane monoterpenoids. C12H17Cl3O3 Colorless oil, [α]D25 = −5.0° (c = 1.3, CHCl3). Source: Sea hare Aplysia punctata (Cádiz, Spain). Pharm: Cytotoxic (P388, ED50 = 2.5 μg/mL, HT29, ED50 = 2.5 μg/mL, A549, ED50 = 1.5 μg/mL, MEL28, ED50 = 1.5 μg/mL). Ref: M. J. Ortega, et al, JNP, 1997, 60, 482 Cl

Cl

O

Cl

O O

8 Anverene Type: Halogenated dimethyloctane monoterpenoids. C10H15Br3Cl2 Cryst., [α]D25 = −12° (c = 0.25, CHCl3). Source: Red alga Plocamium cartilagineum (psychrophilic, cold water,

1.2 Halogenated Dimethyloctane Monoterpenoids

3

Antarctic). Pharm: Antibacterial (VREF, IZD = 8 mm). Ref: S. Ankisetty, et al, JNP, 2004, 67, 1295│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev) Cl

Br

Br Cl

Br

9 Aplysiapyranoid A Type: Halogenated dimethyloctane monoterpenoids. C10H15Br2ClO Oil, [α]D = +4.4° (c = 1, CHCl3). Source: Sea hare Aplysia kurodai. Pharm: Cytotoxic (Vero, MDCK and B16 cells, IC50 = 19–96 μg/mL). Ref: T. Kusumi, et al, JOC, 1987, 52, 4597 Br

Br 2

O

Cl

10 Aplysiapyranoid B Type: Halogenated dimethyloctane monoterpenoids. C10H15Br2ClO Crystal (EtOH), mp 46–49 °C, [α]D = −27° (c = 0.91, CHCl3). Source: Sea hare Aplysia kurodai. Pharm: Cytotoxic (Vero, MDCK and B16 cells, IC50 = 19–96 μg/mL). Ref: T. Kusumi, et al, JOC, 1987, 52, 4597 Br

Br 2

O

Cl

11 Aplysiapyranoid C Type: Halogenated dimethyloctane monoterpenoids. C10H15BrCl2O [α]D25 = +52° (c = 1.0, CHCl3). Source: Sea hare Aplysia kurodai. Pharm: Cytotoxic (Vero, MDCK and B16 cells, IC50 = 19–96 μg/mL). Ref: T. Kusumi, et al, JOC, 1987, 52, 4597 Cl

Br 2

Cl

O

12 Aplysiapyranoid D Type: Halogenated dimethyloctane monoterpenoids. C10H15BrCl2O Oil, [α]D = +3.4° (c = 1.1, CHCl3). Source: Sea hare Aplysia kurodai. Pharm: Cytotoxic (Vero, MDCK and B16 cells, IC50 = 19–96 μg/mL); cytotoxic (hmn tumor cells, IC50 = 14 μg/mL). Ref: T. Kusumi, et al, JOC, 1987, 52, 4597

4

1 Monoterpenoids

Cl

Br 2

Cl

O

13 6-Bromo-3-(bromomethyl)-2,3-dichloro-7-methyl-1,6-octadiene Type: Halogenated dimethyloctane monoterpenoids. C10H14Br2Cl2 [α]D = −6.7° (c = 1, CHCl3). Source: Red alga Portieria hornemannii. Pharm: Cytotoxic (NCI Primary Antitumor Screen, mean GI50 = 0.691 μmol/L, TGI = 3.02 μmol/L, mean LC50 = 13.5 μmol/L). Ref: R. W. Fuller, et al, JMC, 1994, 37, 4407│M. E. Jung, et al, JOC, 1997, 62, 7094 Br

Cl

Cl

Br

14 6-Bromo-3-bromomethyl-3,7-dichloro-7-methyl-1-octene Type: Halogenated dimethyloctane monoterpenoids. C10H16Br2Cl2 Source: Red alga Portieria hornemannii. Pharm: Cytotoxic (NCI Primary Antitumor Screen, mean GI50 = 26.1 μmol/L, TGI = 77.0 μmol/L, mean LC50 > 100 μmol/L, same cytotoxic profile with halomon). Ref: R. W. Fuller, et al, JMC, 1992, 35, 3007; 1994, 37, 4407 Br

Cl

Cl

Br

15 3,4-erythro-1-Bromo-7-dichloromethyl-3-methyl-3,4,8-trichloro-1(E),5(E), 7(E)-octatriene Type: Halogenated dimethyloctane monoterpenoids. C10H10BrCl5 [α]D25 = −22.9° (c = 0.9, CHCl3). Source: Red alga Plocamium cartilagineum sea hare Aplysia dactylomela. Pharm: Antibacterial; algicide. Ref: J. S. Mynderse, et al, Tetrahedron, 1975, 31, 1963│M. Wessels, et al, JNP 2000, 63, 920 Cl

Cl Cl Br

Cl

Cl

16 3-Bromomethyl-3-chloro-7-methyl-1,6-octadiene Type: Halogenated dimethyloctane monoterpenoids. C10H16BrCl Oil, [α]D25 = −3.7° (c = 15, CH2Cl2). Source: Red alga Portieria hornemanni. Pharm: Cytotoxic (NCI Primary

1.2 Halogenated Dimethyloctane Monoterpenoids

5

Antitumor Screen, mean GI50 = 33.1 μmol/L, TGI > 100 μmol/L, mean LC50 > 100 μmol/L). Ref: R. W. Fuller, et al, JMC, 1992, 35, 3007; 1994, 37, 4407│M. E. Jung, et al, JOC, 1997, 62, 7094 Br

Cl

17 3-(Bromomethyl)-2,3-dichloro-7-methyl-1,6-octadiene Type: Halogenated dimethyloctane monoterpenoids. C10H15BrCl2 Oil, [α]D = −1.6° (c = 3, CHCl3). Source: Red alga Portieria hornemannii. Pharm: Cytotoxic (NCI Primary Antitumor Screen, mean GI50 = 47.0 μmol/L, TGI > 100 μmol/L, mean LC50 > 100 μmol/L, same cytotoxic profile with halomon). Ref: R. W. Fuller, et al, JMC, 1994, 37, 4407 Br

Cl

Cl

18 Z-3-Bromomethylene-2-chloro-7-methyl-1,6-octadiene Type: Halogenated dimethyloctane monoterpenoids. C10H14BrCl Source: Red alga Portieria hornemannii. Pharm: Cytotoxic (NCI Primary Antitumor Screen, mean GI50 = 19.5 μmol/L, TGI = 44.7 μmol/L, mean LC50 > 100 μmol/L, same cytotoxic profile with halomon). Ref: R. W. Fuller, et al, JMC, 1992, 35, 3007; 1994, 37, 4407 Br

Cl

19 3-(Bromomethyl)-2,3,6-trichloro-7-methyl-1,6-octadiene Type: Halogenated dimethyloctane monoterpenoids. C10H14BrCl3 Oil. Source: Red algae Portieria hornemanni and Chondrococcus hornemanni. Pharm: Cytotoxic (NCI Primary Antitumor Screen, mean GI50 = 0.741 μmol/L, TGI = 3.39 μmol/L, mean LC50 = 17.0 μmol/L). Ref: R. W. Fuller, et al, JMC, 1994, 37, 4407 Cl

Cl

Br

Cl

6

1 Monoterpenoids

20 (1E,3R,4S,5E)-8-Bromo-1,3,4,7-tetrachloro-7-chloromethyl-3-methyl-1, 5-octadiene Type: Halogenated dimethyloctane monoterpenoids. C10H12BrCl5 Oil, [α]D = −20.2° (c = 1.19, CHCl3). Source: Red algae Plocamium spp. including Plocamium oregonum, Plocamium cartilagineum and Pantoneura plocamioides, sea hare Aplysia californica (digestive gland). Pharm: Antifungal; insecticide. Ref: C. Ireland, et al, JOC, 1976, 41, 2461│P. Crews, JOC, 1977, 42, 2634│D. B. Stierle, et al, Tetrahedron, 1979, 35, 2855│J. Rovirosa, et al, Bol. Soc. Chil. Quim., 1990, 35, 131│M. Cueto, et al, Tetrahedron, 1998, 54, 3575Cl

Cl

Br

Cl

Cl Cl

21 8-Bromo-1,3,4,7-tetrachloro-3,7-dimethyl-1,5-octadiene Type: Halogenated dimethyloctane monoterpenoids. C10H13BrCl4 Oil, [α]D = −48.8° (c = 0.86, CHCl3). Source: Red algae Plocamium spp. (Antarctic). Pharm: Antifungal. Ref: D. B. Stierle, et al, Tetrahedron, 1979, 35, 2855 Cl

Cl

Cl Cl

Br

22 Cartilagineal Type: Halogenated dimethyloctane monoterpenoids. C10H11Cl3O Viscous liquid, bp0.1 mmHg 130 °C. Source: Red alga Plocamium cartilagineum. (Visinity of Santa Cruz, 400 miles northwest of La Jolla), sea hare Aplysia californica. Pharm: Ichthyotoxin. Ref: P. Crews, et al, JOC, 1974, 39, 3303│P. Crews, et al, Phytochemistry, 1984, 23, 1449 H

O

Cl

Cl Cl

23 (1E,3R,4S,5E,7S)-1,8-Dibromo-3,4,7-trichloro-3,7-dimethyl-1,5-octadiene Type: Halogenated dimethyloctane monoterpenoids. C10H13Br2Cl3 Cryst., mp 48.5–49 °C, [α]D = −46.3° (c = 1.03, CHCl3). Source: Red algae Plocamium spp., sea hare Aplysia californica (California). Pharm: Antifungal. Ref: D. B. Stierle, et al, Tetrahedron, 1979, 35, 2855

1.2 Halogenated Dimethyloctane Monoterpenoids

7

Br Cl Br

Cl Cl

24 Halomon Type: Halogenated dimethyloctane monoterpenoids. C10H15Br2Cl3 Cryst. (MeOH), mp 49–50 °C, [α]D = +206° (c = 1.1, CH2Cl2). Source: Red alga Portieria hornemanni. Pharm: Cytotoxic (NCI Primary Antitumor Screen, mean GI50 = 0.676 μmol/L, TGI = 3.02 μmol/L, mean LC50 = 11.5 μmol/L). Ref: R. W. Fuller, et al, JMC, 1992, 35, 3007; 1994, 37, 4407│T. Schlama, et al, Angew. Chem., Int. Ed., 1998, 37, 2085│T. Sotokawa, et al, Angew. Chem., Int. Ed., 2000, 39, 3430 Br

Cl

Cl

Br

Cl

25 Isohalomon 7-Bromo-3-bromomethyl-2,3,6-trichloro-7-methyl-1-octene Type: Halogenated dimethyloctane monoterpenoids. C10H15Br2Cl3 Cryst., [α]D = −25° (c = 1, CHCl3). Source: Red algae Portieria hornemanni and Chondrococcus hornemanni (Hawaii, Black Point). Pharm: Cytotoxic (NCI Primary Antitumor Screen, mean GI50 = 1.32 μmol/L, TGI = 4.47 μmol/L, mean LC50 = 16.2 μmol/L, same cytotoxic profile with halomon). Ref: B. J. Burreson, et al, Chem. Letters, 1975, 1111│R. W. Fuller, et al, JMC, 1992, 35, 3007; 1994, 37, 4407 Br Cl

Br

Cl

Cl

26 (2R,3E,6R,7S)-1,1,7-Tribromo-2,6,8-trichloro-3,7-dimethyl-3-octene Type: Halogenated dimethyloctane monoterpenoids. C10H14Br3Cl3 Cryst. (EtOH), mp 60.5–61.5 °C, [α]D25 = +99° (c = 0.0002, cyclohexane). Source: Red algae Plocamium cruciferum (New Zealand) and Plocamium cartilagineum (New Zealand). Pharm: Antimicrobial. Ref: J. W. Blunt, et al, Tet. Lett., 1978, 4417│P. Bates, et al, Aust. J. Chem., 1979, 32, 2545│J. W. Blunt, et al, Aust. J. Chem., 1985, 38, 519 Br Cl

Br Br

Cl

Cl

8

1 Monoterpenoids

1.3 Ochtodane Monoterpenoids 27 4-Bromo-1,6,8-trichloro-2-ochtodene Type: Ochtodane monoterpenoids. C10H14BrCl3 Source: Red alga Portieria hornemanni. Pharm: Cytotoxic (NCI Primary Antitumor Screen, mean GI50 = 1.15 μmol/L, TGI = 4.68 μmol/L, mean LC50 = 20.0 μmol/L). Ref: R. W. Fuller, et al, JMC, 1992, 35, 3007; 1994, 37, 4407

Cl

Cl

Br

Cl

28 1,6-Dibromo-2-chloro-3(8)-ochtoden-4-ol Type: Ochtodane monoterpenoids. C10H15Br2ClO Oil, [α]D20 = −26.8° (c = 1, CHCl3). Source: Red alga Ochtodes crockeri. Pharm: Antifeedant (herbivorous fish Pomacentrus coeruleus). Ref: V. J. Paul, et al, JOC, 1980, 45, 3401 Br

OH

Cl Br

29 (1E,6S*,8S*)-1,6-Dibromo-8-chloro-1,3-ochtodiene Type: Ochtodane monoterpenoids. C10H13Br2Cl Oil, [α]D20 = +16.7° (c = 5.4, CHCl3). Source: Red alga Ochtodes crockeri. Pharm: Antifeedant (herbivorous fish Pomacentrus coeruleus). Ref: V. J. Paul, et al, JOC, 1980, 45, 3401 Br

Br

Cl

30 (1E,4S*,6S*)-1,6-Dibromo-1,3(8)-ochtodien-4-ol Type: Ochtodane monoterpenoids. C10H14Br2O Oil, [α]D20 = −71.2° (c = 3.2, CHCl3). Source: Red alga Ochtodes crockeri. Pharm: Antifeedant (herbivorous fish Pomacentrus coeruleus). Ref: V. J. Paul, et al, JOC, 1980, 45, 3401

1.3 Ochtodane Monoterpenoids

9

Br OH

1 3 8

Br

31 (1E,4R*,6S*)-1,6-Dibromo-1,3(8)-ochtodien-4-ol Type: Ochtodane monoterpenoids. C10H14Br2O Oil, [α]D20 = −45.4° (c = 2.5, CHCl3). Source: Red alga Ochtodes crockeri. Pharm: Antifeedant (herbivorous fish Pomacentrus coeruleus). Ref: V. J. Paul, et al, JOC, 1980, 45, 3401 Br OH

Br

32 1,3(8)-Ochtodien-5,6-diol Type: Ochtodane monoterpenoids. C10H16O2 Source: Red alga Ochtodes crockeri. Pharm: Antifeedant (herbivorous fish Pomacentrus coeruleus). Ref: V. J. Paul, et al, JOC, 1980, 45, 3401 HO HO

33 2Z,4-Ochtodien-1,6-diol Type: Ochtodane monoterpenoids. C10H16O2 Source: Red alga Ochtodes crockeri. Pharm: Antifeedant (herbivorous fish Pomacentrus coeruleus). Ref: V. J. Paul, et al, JOC, 1980, 45, 3401│Y. Masaki, et al, Bill. Chem. Soc. Jpn., 1984, 57, 3466 OH

HO

34 1,6,8-Tribromo-2-chloro-3(8)-ochtodene Type: Ochtodane monoterpenoids. C10H14Br3Cl Oil, [α]D = +55° (c = 0.74, CHCl3). Source: Red algae Ochtodes secundiramea (Tobago) and Portieria hornemannii. Pharm: Cytotoxic (NCI Primary Antitumor Screen, mean GI50 = 21.9 μmol/L,

10

1 Monoterpenoids

TGI = 45.7 μmol/L, mean LC50 = 93.3 μmol/L). Ref: W. H. Gerwick, Phytochemistry, 1984, 23, 1323│R. W. Fuller, et al, JMC, 1992, 35, 3007; 1994, 37, 4407 Br Cl Br

Br

35 1,6,8-Trichloro-2,4-ochtodadiene Type: Ochtodane monoterpenoids. C10H13Cl3 Source: Red alga Portieria hornemanni. Pharm: Cytotoxic (NCI Primary Antitumor Screen, mean GI50 = 20.0 μmol/L, TGI = 47.9 μmol/L, mean LC50 > 100 μmol/L). Ref: R. W. Fuller, et al, JMC, 1992, 35, 3007; 1994, 37, 4407

Cl

Cl

Cl

1.4 1-Ethyl-1,3-Dimethylcyclohexane Monoterpenoids 36 Aplysiaterpenoid A Gelidene Type: 1-Ethyl-1,3-dimethylcyclohexane monoterpenoids. C10H14Cl4 Cryst., mp 86–88 °C, mp 82 °C, [α]D = +9.4° (c = 0.01, CHCl3). Source: Red algae Gelidium sesquipedale and Plocamium hamatum, sea hare Aplysia kurodai. Pharm: Antifeedant; insecticide. Ref: T. Miyamoto, et al, Annalen, 1988, 1191│J. C. Coll, et al, Aust. J. Chem., 1988, 41, 1743│M. A. Aazizi, et al, JNP, 1989, 52, 829│R. De Nys, et al, Mar. Biol. (Berlin), 1991, 108, 315│G. M. König, et al, Phytochemistry, 1999, 52, 1047 Cl Cl 1

Cl

5

Cl

37 4-Bromo-5-bromomethyl-1-(2-chloroethenyl)-2,5-dichloro-1-methylcyclohexane Type: 1-Ethyl-1,3-dimethylcyclohexane monoterpenoids. C10H13Br2Cl3 mp 75–76 °C, mp 74–74.5 °C, [α]D25 = −61.4° (c = 0.21, CHCl3). [α]D20 = −43.8° (c = 1.01, CHCl3), [α]D = −67°. Source: Red algae Plocamium cartilagineum (Antarctic and south coast

1.4 1-Ethyl-1,3-Dimethylcyclohexane Monoterpenoids

11

of England) and Plocamium hamatum (Great Barrier Reef), sea hare Aplysia dactylomela. Pharm: Antifoulant (Chlorella fusca, IZD = 16 mm); antifungal (Ustilago violacea, IZD = 1 mm, Mycotypha microspora, IZD = 2 mm); antibacterial (Bacillus megaterium, IZD = 2 mm); algicide (strong); toxic (brine shrimp). Ref: M. D. Higgs, et al, Tetrahedron, 1977, 33, 2775│D. B. Stierle, et al, Tetrahedron, 1979, 35, 1261│G. M. König, et al, Phytochemistry, 1999, 52, 1047│M. Wessels, et al, JNP 2000, 63, 920 Cl

Br Cl Br

Cl

38 4-Chloro-5-(2-chloroethenyl)-1-chloromethyl-5-methylcyclohexene Type: 1-Ethyl-1,3-dimethylcyclohexane monoterpenoids. C10H13Cl3 Oil, [α]D = −110° (c = 0.91, CHCl3). Source: Red alga Plocamium cartilagineum (Antarctic). Pharm: Antifungal. Ref: D. B. Stierle, et al, Tetrahedron, 1979, 35, 1261 Cl

Cl Cl

39 Mertensene Mertensene 1 Type: 1-Ethyl-1,3-dimethylcyclohexane monoterpenoids. C10H14BrCl3 Needles (hexane), mp 105.5–106 °C, [α]D = +20° (c = 0.3, CHCl3). Source: Red algae Plocamium mertensii and Plocamium hamatum, sea hare Aplysia punctata. Pharm: Antibacterial; algicide; insecticide; sedative; smooth muscle relaxant; anticonvulsant. Ref: R. S. Norton, et al, Tet. Lett., 1977, 3905│R. J, Capon., Aust. J. Chem., 1984, 37, 537│G. M. Konig, et al, Phytochemistry, 1991, 52, 1047 Cl

Cl Cl

Br

40 Plocamene D 2,4-Dichloro-1-(2-chloroethenyl)-1-methyl-5-methylenecyclohexane Type: 1-Ethyl-1,3dimethylcyclohexane monoterpenoids. C10H13Cl3 Oil, [α]D20 = −4.1° (c = 0.73, CHCl3). Source: Red algae Plocamium violaceum and Microcladia spp. Pharm: Antifungal. Ref: P. Crews, et al, JOC, 1978, 43, 116; 1984, 49, 1371

12

1 Monoterpenoids

Cl

Cl

Cl

41 Plocamene D’ 4-Bromo-2-chloro-1-(2-chloroethenyl)-1-methyl-5-methylenecyclohexane Type: 1-Ethyl1,3-dimethylcyclohexane monoterpenoids. C10H13BrCl2 Oil, [α]D = +31.3° (c = 0.86, CHCl3). Source: Red algae Plocamium violaceum, Plocamium hamatum, Plocamium meitensii and Plocamium cartilagineum (Antarctic). Pharm: Antifungal. Ref: P. Crews, et al, JOC, 1978, 43, 716│D. B. Stierle, et al, Tetrahedron, 1979, 35, 1261│G. M. König, et al, Phytochemistry, 1999, 52, 1047│D. Dias, et al, Phytochem. Anal., 2008, 19, 453 Cl

Br

Cl

42 epi-Plocamene D Type: 1-Ethyl-1,3-dimethylcyclohexane monoterpenoids. C10H13Cl3 Oil, [α]D = −63.3° (c = 0.98, CHCl3). Source: Red algae Plocamium violaceum, and Plocamium cartilagineum (Antarctic). Pharm: Antifungal. Ref: D. B. Stierle, et al, Tetrahedron, 1979, 35, 1261 Cl 4

Cl

Cl

43 (1S,2R,4R,5S)-1,2,4-Trichloro-5-(2-chloroethenyl)-1,5-dimethylcyclohexane Type: 1-Ethyl-1,3-dimethylcyclohexane monoterpenoids. C10H14Cl4 Oil or cryst. (Me2CO). Source: Red algae Plocamium cartilagineum (Chile) and Plocamium hamatum. Pharm: Antibacterial; toxin (necrotic to soft corals). Ref: A. San-Martin, et al, Phytochemistry, 1991, 30, 2165│R. De Nys, et al, Mar. Biol. (Berlin), 1991, 108, 315│P. Rivera, et al, Acta Cryst. C, 1998, 54, 816│G. M. König, et al, Phytochemistry, 1999, 52, 1047

1.5 1-Ethyl-2,4-Dimethylcyclohexane Monoterpenoids

13

Cl Cl

Cl

Cl

44 (1S,2R,4S,5S)-1,2,4-Trichloro-5-(2-chloroethenyl)-1,5-dimethylcyclohexane Type: 1-Ethyl-1,3-dimethylcyclohexane monoterpenoids. C10H14Cl4 Cryst., mp 57–58 °C, [α]D70 = +7.7° (c = 1, CHCl3). Source: Red alga Plocamium cartilagineum (Chile). Pharm: Insecticide; acaricide. Ref: A. San-Martin, et al, Phytochemistry, 1991, 30, 2165│R. De Nys, et al, Mar. Biol. (Berlin), 1991, 108, 315│G. M. König, et al, Phytochemistry, 1999, 52, 1047 Cl Cl

Cl

Cl

45 (1S,2R,4R,5R)-1,2,4-Trichloro-5-(2-chloroethenyl)-1,5-dimethylcyclohexane Type: 1-Ethyl-1,3-dimethylcyclohexane monoterpenoids. C10H14Cl4 Cryst. (hexane), mp 105 °C. Source: Red alga Plocamium cartilagineum (Chile). Pharm: Insecticide; acaricide; antifungal. Ref: A. San-Martin, et al, Phytochemistry, 1991, 30, 2165│P. Rivera, et al, Acta Crystallogr. Sect. C, 1998, 54, 816 Cl Cl

Cl

Cl

1.5 1-Ethyl-2,4-Dimethylcyclohexane Monoterpenoids 46 1,4-Dibromo-5-chloro-2-(2-chloroethenyl)-1,5-dimethylcyclohexane Type: 1-Ethyl-2,4-dimethylcyclohexane monoterpenoids. C10H14Br2Cl2 mp 86–87 °C, [α]D = −46.1° (c = 0.345, CHCl3), [α]D20 = −36° (c = 1.13, CHCl3). Source: Red alga Plocamium cartilagineum (English Channel, Australia and Spain), sea hares Aplysia punctata and Aplysia dactylomela. Pharm: Antibacterial; antifungal; toxic (brine shrimp). Ref: M. D. Higgs, et al, Tetrahedron, 1977, 33, 2775│R. S. Norton, et al, Tet.

14

1 Monoterpenoids

Lett., 1977, 3905│A. G. Gonzales, et al, Phytochemistry, 1978, 17, 947│M. Wessels, et al, JNP 2000, 63, 920 Br

Cl Br

Cl

1.6 Iridoid Monoterpenoids 47 Cerbinal Type: Iridoid monoterpenoids. C11H8O4 Yellow needles (MeOH), mp 188–189 °C. Source: Semimangrove Cerbera manghas. Pharm: Antifungal. Ref: Abe, F. et al, Chem. Pharm. Bull., 1977, 25, 3422│Ohashi, H. et al, Agric. Biol. Chem., 1986, 50, 2655│Zhang, X. et al, Zhongcaoyao, 2008, 39, 1138; CA, 151, 443681 O

O

O H

O

48 Fulvoplumierin Type: Iridoid monoterpenoids. C14H12O4 Orange needles (CHCl3/EtOH), mp 151–152 °C (dec), Sol. Me2CO, Py, CHCl3; fairly sol. MeOH, C6H6, Et2O, EtOAc, EtOH, butanol; poorly sol. H2O, hexane. Source: Prosobranch (Marine snail) Nerita albicilla. Pharm: Antibacterial; anti-HIV. Ref: G. Buchi, et al, JACS, 1968, 90, 5336; 1969, 91, 6470│R. Sanduja, et al, JNP, 1985, 48, 335│CRC Press, DNP on DVD, 2012, version 20.2 O

O

O O

49 Plumericin Type: Iridoid monoterpenoids. C15H14O6 Platelike needles (C6H6), mp 212.5–213.5 °C (slightly dec), [α]D30 = +204° (CHCl3). Source: Sponge Cliona caribboea (burrowing sponge), terrestrial plants (Plumeria spp.). Pharm: Antibiotic; antifungal; antineoplastic. Ref: G. E. Martin, et al, JOC, 1985, 50, 2383│Merck Index, 10th Edition, Entry No. 7407

1.7 Menthane Monoterpenoids

O

H O

15

O

O H H

H O

O

1.7 Menthane Monoterpenoids 50 Hydrallmanol A Type: Menthane monoterpenoids. C22H28O2 Pale yellow oil. Source: Hydroid Hydrallmania falcata. Pharm: Cytotoxic. Ref: C. Pathirana, et al, Tet. Lett., 1989, 30, 1487 OH

OH

2 Sesquiterpenoids 2.1 Farnesane Sesquiterpenoids 51 (3E)-6-Acetoxy-3,11-dimethyl-7-methylidendodeca-1,3,10-triene Type: Simple farnesane sesquiterpenoids. C17H26O2 Source: Gorgonian Plexaurella grisea (Caribbean Sea). Pharm: Cytotoxic (P388, IC50 = 2.5 μg/mL; A549, IC50 = 5 μg/ mL; HT29, IC50 = 5 μg/mL; MEL28, IC50 = 5 μg/mL). Ref: A. Rueda, et al, JNP, 2001, 64, 401 O O 7

3E

52 Caulerpenyne Type: Simple farnesane sesquiterpenoids. C21H26O6 Cryst., mp 57–58 °C, [α]D20 = +7.1° (c = 1, EtOH). Source: Green algae Caulerpa taxifolia (tropical, Cap Martin, France) and Caulerpa prolifera (tropical). Pharm: Antimicrobial; toxic. Ref: V. Amico, et al, Tet. Lett., 1978, 3593│T. Nakatsu, et al, JOC, 1981, 46, 2435│L. De Napoli, et al, Phytochemistry, 1982, 21, 782│A. Guerriero, et al, Helv. Chim. Acta, 1992, 75, 689; 1993, 76, 855; 1995, 78, 1755 O O

14

7 11

10

15

2

O

O

1

O O

53 Caulerpenynol 6-Hydroxy-Δ7(14)-caulerpenyne Type: Simple farnesane sesquiterpenoids. C21H26O7 Oil, [α]D20 = −53.7° (c = 0.095, EtOH). Source: Green alga Caulerpa taxifolia (tropical, Cap Martin, France). Pharm: Mutagen. Ref: A. Guerriero, et al, Helv. Chim. Acta, 1993, 76, 855

https://doi.org/10.1515/9783110655131-002

18

2 Sesquiterpenoids

O O

14

15

6

2

7 11

O

OH

10

1

O

O

O

54 2,3-Dihydroxypropyl-farnesicate Type: Simple farnesane sesquiterpenoids. C18H30O4 Oil. Source: Nudibranch Archidoris odhneri. Pharm: Antibacterial (Staphylococcus aureus). Ref: R. J. Andersen, et al, Tet. Lett., 1980, 21, 797 O

OH O OH

55 10,11-Epoxycaulerpenyne Type: Simple farnesane sesquiterpenoids. C21H26O7 Oil, mp 57–58 °C, [α]D = −12.3° (c = 0.56, EtOH). Source: Green alga Caulerpa taxifolia (tropical, Monaco region of Mediterranean). Pharm: Toxic; mutagenic. Ref: V. Amico, et al, Tet. Lett., 1978, 3593│A. Guerriero, et al, Helv. Chim. Acta, 1992, 75, 689 O O

14

O

7

11

O

15

10

O

O

1

O

56 Flexilin Type: Simple farnesane sesquiterpenoids. C19H28O4 bp0.1mmHg 100 °C. Source: Green alga Caulerpa flexilis (Tasmania). Pharm: Ichthyotoxin. Ref: A. J. Blackman, et al, Tetrahedron Lett, 1978, 3063 O 14

O 4

O O

2.1 Farnesane Sesquiterpenoids

19

57 Oxytoxin 1 Type: Simple farnesane sesquiterpenoids. C19H24O5 Oil, [α]D25 = −70.6° (c = 2, CHCl3). Source: Green alga Caulerpa taxifolia, sacoglossans Oxynoe olivacea, Ascobulla fragilis and Lobiger serradifalci. Pharm: Ichthyotoxin; toxic (brine shrimp). Ref: G. Cimino, et al, Experientia, 1990, 46, 767│A. Guerriero, et al, Helv. Chim. Acta, 1992, 75, 689; 1993, 76, 855│M. Gavagnin, et al, J. Exp. Mar. Biol. Ecol., 1994, 175, 197 O O

O H

O

O

58 Preraikovenal Type: Simple farnesane sesquiterpenoids. C15H24O2 Source: Protist ciliate Euplotes raikovi. Pharm: Putative biogenetic precursor of Raikovenal. Ref: G. Guella, et al, J. Chem. Soc., Chem. Commun., 1994, 2585│B. B. Snider, et al, Synth. Commun., 1997, 27, 1583 OH H O

59 Preuplotin Type: Simple farnesane sesquiterpenoids. C19H26O5 Source: Protist ciliate Euplotes crassus. Pharm: Cytotoxic (to ciliates). Ref: G. Guella, et al, JCS Perkin I, 1994, 161 O

14

O

O 4

O O

60 Rhipocephalin Type: Simple farnesane sesquiterpenoids. C21H28O6 Oil, [α]D = 0°, extremely unstable. Source: Green alga Rhipocephalus phoenix. Pharm: Toxic (marine fish Pomacentrus coeruleus, at 2 μg/mL). antifeedant (Eupomacentrus leucostictus, 100–300 μg/g of food pellet). Ref: H. H. Sun, et al, Tetrahedron Lett, 1979, 685

20

2 Sesquiterpenoids

O O

O O

O O

61 Rhipocephenal Type: Simple farnesane sesquiterpenoids. C15H20O3 Oil. Source: Green alga Rhipocephalus phoenix (stored sample). Pharm: Toxic (marine fish Pomacentrus coeruleus, 10 μg/mL). antifeedant (Eupomacentrus leucostictus, 100–300 μg/g of food pellet). Ref: H. H. Sun, et al, Tetrahedron Lett, 1979, 685 H HO

O

O H

62 Sinularianin E Type: Simple farnesane sesquiterpenoids. C16H24O4 Source: Soft coral Sinularia sp. (Dongluo I., Hainan Province, China). Pharm: NF-κB inhibitor (mild). Ref: B. Yang, et al, Mar. Drugs, 2013, 11, 4741 O O HO

O

63 (3Z,5E)-3,7,11-Trimethyl-9-oxododeca-1,3,5-triene Type: Simple farnesane sesquiterpenoids. C15H24O Source: Gorgonian Plexaurella grisea (Caribbean Sea). Pharm: Cytotoxic (P388, IC50 = 2.5 μg/mL; A549, IC50 = 2.5 μg/mL; HT29, IC50 = 2.5 μg/mL; MEL28, IC50 = 2.5 μg/mL). Ref: A. Rueda, et al, JNP, 2001, 64, 401

O

64 (3E,5E)-3,7,11-Trimethyl-9-oxododeca-1,3,5-triene Type: Simple farnesane sesquiterpenoids. C15H24O Source: Gorgonian Plexaurella grisea (Caribbean Sea). Pharm: Cytotoxic (P388, IC50 = 2.5 μg/mL; A549,

2.1 Farnesane Sesquiterpenoids

21

IC50 = 5 μg/mL; HT29, IC50 = 5 μg/mL; MEL28, IC50 = 5 μg/mL). Ref: A. Rueda, et al, JNP, 2001, 64, 401

O

65 (2E,4E,7Z)-2,6,10-Trimethylundeca-2,4,7,9-tetraenal Type: Simple farnesane sesquiterpenoids. C14H20O Source: Gorgonian Plexaurella grisea (Caribbean Sea). Pharm: Cytotoxic (P388, A549, HT29 and MEL28 cells, all IC50 > 10 μg/mL). Ref: A. Rueda, et al, JNP, 2001, 64, 401 O

66 (2E,4E)-2,6,10-Trimethylundeca-2,4,9-trienal Type: Simple farnesane sesquiterpenoids. C14H22O Source: Gorgonian Plexaurella grisea (Caribbean Sea). Pharm: Cytotoxic (P388, IC50 = 0.5 μg/mL; A549, IC50 = 2.5 μg/mL; HT29, IC50 = 2.5 μg/mL; MEL28, IC50 = 2.5 μg/mL). Ref: A. Rueda, et al, JNP, 2001, 64, 401 O

67 Capilloquinol Type: Furanoid farnesane sesquiterpenoids. C22H26O3 Colorless, viscous oil, [α]D25 = +31° ( c = 0.1, CHCl3). Source: Soft coral Sinularia capillosa (depth of 8–10 m, Dongsha Atoll, Taiwan). Pharm: Cytotoxic (P388 cells, ED50 = 3.8 μg/mL, A549 and HT29, inactive). Ref: S. -Y. Cheng, et al, Mar. Drugs, 2011, 9, 1469

H O

OH

O

68 Dendrolasin 3-(4,8-Dimethyl-3,7-nonadienyl)furan Type: Furanoid farnesane sesquiterpenoids. C15H22O Oil, bp16mmHg 148–150 °C, nD20 = 1.4860. Source: Sponge Oligoceras hemorrhages, dorid nudibranch Cadlina luteomarginata (California), terrestrial ant

22

2 Sesquiterpenoids

(Dendrolasius fuliginosus). Pharm: Antifeedant. Ref: D. J. Wanderah, et al, Lloydia, 1975, 38, 271│J. E. Thompson, et al, Tetrahedron, 1982, 38, 1865 O

69 Dictyodendrillin A 1,2-Epoxy-6,10-farnesadien-15,1-olide Type: Furanoid farnesane sesquiterpenoids. C15H22O3 Oil, [α]D = +0.2° (c = 1.6, CHCl3), [α]D = −0.2° (c = 1.35, MeOH). Source: Sponge Dictyodendrilla sp. (Australia). Pharm: Antibiotic. Ref: N. H. Tran, et al, Aust. J. Chem., 1995, 48, 1757 O

10

O O

6

70 Dictyodendrillin B 15-Hydroxy-2,6,10-farnesatrien-1,15-olide Type: Furanoid farnesane sesquiterpenoids. C15H22O3 Source: Sponge Dictyodendrilla sp. (Australia). Pharm: Antibiotic. Ref: N. H. Tran, Aust. J. Chem., 1995, 48, 1757│K. Gerlach, et al, Synlett, 1998, 682

O HO

O

71 Dictyodendrillin C 1-Hydroxy-2,6,10-farnesatrien-15,1-olide Type: Furanoid farnesane sesquiterpenoids. C15H22O3 Source: Sponge Dictyodendrilla sp. (Australia). Pharm: Antibiotic. Ref: N. H. Tran, et al, Aust. J. Chem., 1995, 48, 1757 O

O OH

72 (3E,7E)-5-(2,6-Dimethyl-1,5,7-octatrienyl)-3-furancarboxylic acid 9,13-Epoxy-1,3,7,9,11(13)-farnesapentaen-12-oic acid Type: Furanoid farnesane sesquiterpenoids. C15H18O3 Cryst., mp 94.5–95.5 °C. Source: Soft corals Sinularia capillosa and Sinularia spp. Pharm: Anti-inflammatory. Ref: B. F. Bowden, et al, Aust. J. Chem., 1983, 36, 371

2.1 Farnesane Sesquiterpenoids

23

O HO O

8

7

3

73 8-Hydroxydendrolasin Type: Furanoid farnesane sesquiterpenoids. C15H22O2 Oil, [α]D = +15.5° (c = 4 × 10−3, MeOH). Source: Ascidian Ritterella rete. Pharm: Cytotoxic (P388, in vitro, IC50 = 1 μg/mL). Ref: L. A. Lenis, et al, Tetrahedron, 1998, 54, 5385 OH

O

74 Sinularianin F Type: Furanoid farnesane sesquiterpenoids. C16H24O3 Source: Soft coral Sinularia sp. (Dongluo I., Hainan Province, China). Pharm: NF-κB inhibitor (mild). Ref: B. Yang, et al, Mar. Drugs, 2013, 11, 4741 O

O

OH

75 Tavacfuran Type: Furanoid farnesane sesquiterpenoids. C15H18O2 Liq. Source: Sponge Dysidea sp., nudibranches Hypselodoris cantabrica, Hypselodoris tricolor and Hypselodoris villafranca. Pharm: Antifeedant. Ref: G. Guella, et al, Helv. Chim. Acta, 1985, 68, 1276

O

O

76 Abscisic acid Abscisin II Type: Cyclofarnesane sesquiterpenoids. C15H20O4 Cryst. (CHCl3/petrol), mp 160–161 °C, [α]D = +430°. Source: Marine-derived fungi Aspergillus sp. from unidentified alga (Indonesia) and Curvularia lunata from sponge Niphates olemda.

24

2 Sesquiterpenoids

Pharm: Abscission-accelerating substance; antagonist of plant growth hormones; LD50 (rat, orl) > 5000 mg/kg. Ref: J. Z. Xu, et al, J. Antibiot., 2008, 61, 415

OH O

O

OH

77 Aplysistatin Type: Cyclofarnesane sesquiterpenoids. C15H21BrO3 Cryst., mp 173–175 °C, [α]D25 = −375° (MeOH). Source: Sea hare Aplysia angasi. Pharm: Antimycobacterial (weak); cytotoxic. Ref: G. M. Koenig, et al, PM, 2000, 66, 337 H O

O

O

Br

H

78 Arenaran A Type: Cyclofarnesane sesquiterpenoids. C15H26O Amorph. solid, mp 54.2 °C, [α]D = +154° (c = 0.01, CHCl3). Source: Sponge Dysidea arenaria (Thailand). Pharm: Cytotoxic (in vitro, A549, IC50 = 9.5 μg/mL, HT29, IC50 = 9.11 μg/mL, HCT29, IC50 = 5.28 μg/mL, murine leukemia, IC50 = 3.17 μg/mL). Ref: P. A. Horton, et al, JNP, 1995, 58, 44 O 10 9

H

79 1,4-Diacetoxy-2-[2-(2,2-dimethyl-6-methylenecyclohexyl)ethyl]-1,3-butadiene Type: Cyclofarnesane sesquiterpenoids. C19H28O4 Viscous oil, [α]D = −3° (c = 0.9, CHCl3). Source: Green alga Caulerpa bikiniensis. Pharm: Cytotoxic; ichthyotoxin; antifeedant. Ref: V. J. Paul, et al, Tet. Lett., 1982, 23, 5017 O O O O

2.2 Cyclopentane Sesquiterpenoids

25

80 Onchidal Type: Cyclofarnesane sesquiterpenoids. C17H24O3 Oil, [α]D22 = +17.2° (c = 1, CHCl3). Source: Pulmonate Onchidella binneyi (shell-less). Pharm: Antimicrobial; toxic (many organisms). Ref: C. Ireland, et al, Bioorg. Chem., 1978, 7, 125

O

O

O

81 Tanyolide A Type: Cyclofarnesane sesquiterpenoids. C22H34O6 Oil, [α]D = 0° (c = 0.1, CHCl3). Source: Mollusc Sclerodoris tanya (La Jolla). Pharm: Toxic. Ref: P. J. Krug, et al, Tetrahedron, 1995, 51, 11063 O O O

O

O O

82 Tanyolide B Type: Cyclofarnesane sesquiterpenoids. C20H32O5 Oil, [α]D = −3.0° (c = 0.1, CHCl3). Source: Mollusc Sclerodoris tanya (La Jolla). Pharm: Antifeedant (fish). Ref: P. J. Krug, et al, Tetrahedron, 1995, 51, 11063

O O

OH

O O

2.2 Cyclopentane Sesquiterpenoids 83 Euplotin C 8-Deoxo-euplotin B Type: Cyclopentane sesquiterpenoids. C17H24O4 Source: Protist ciliate Euplotes crassus. Pharm: Cytotoxic (to ciliates). Ref: G. Guella, et al, JCS Perkin I, 1994, 161

26

2 Sesquiterpenoids

H

10 8

H

O O

H O

O H

2.3 Irregular Acyclic Sesquiterpenoids 84 Kumepaloxane Type: Irregular acyclic sesquiterpenoids. C12H20BrClO Oil, [α]D = +22.6° (c = 0.32, CHCl3). Source: Cephalaspid Haminoea cymbalum. Pharm: Antifeedant (fish); ichthyotoxin. Ref: A. Poiner, et al, Tetrahedron, 1989, 45, 617

Cl

O Br

2.4 Bisabolane Sesquiterpenoids 85 3-Acetoxy-E-γ-bisabolene Type: Bisabolane sesquiterpenoids. C17H26O2 [α]D25 = +1° (c = 0.56, CHCl3). Source: Red alga Laurencia rigida (Australia). Pharm: Antifoulant. Ref: G. M. König, et al, JNP, 1997, 60, 967 O O

86 Aspergiterpenoid A Type: Bisabolane sesquiterpenoids. C15H24O2 White powder; [α]D25 = −4.7° (c = 3.21, CHCl3). Source: Marine-derived fungus Aspergillus sp. from sponge Xestospongia testudinaria (Weizhou coral reef, Giuangxi, China). Pharm: Antibacterial (Staphylococcus albus, MIC > 20 μmol/L, control Ciprofloxacin, MIC = 0.312 μmol/L; Bacillus subtilis, MIC > 20 μmol/L, Ciprofloxacin, MIC = 1.25 μmol/L; Bacillus cereus, MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.625 μmol/L; Sarcina lutea, MIC > 20 μmol/L, Ciprofloxacin, MIC = 2.50 μmol/L; Escherichia coli, MIC = 20.0 μmol/L, Ciprofloxacin, MIC = 0.625 μmol/L; Micrococcus tetragenus, MIC = 10.0 μmol/L, Ciprofloxacin,

2.4 Bisabolane Sesquiterpenoids

27

MIC = 0.160 μmol/L; Vibrio Parahaemolyticus, MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.312 μmol/L; Vibrio anguillarum, MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.312 μmol/L); cytotoxic (HL60 and A549 cells, IC50 > 50 μg/mL, weak). Ref: D. Li, et al, Mar. Drugs, 2012, 10, 234 HO

OH

87 Caespitane Type: Bisabolane sesquiterpenoids. C15H25Br2ClO Cryst., mp 82–84 °C, [α]D = +39.8° (c = 0.89, CHCl3). Source: Red alga Laurencia caespitosa, sea hare Aplysia dactylomela. Pharm: Toxic (brine shrimp); algicide. Ref: M. Chang, et al, Phytochemistry, 1989, 28, 1417│M. Wessels, et al, JNP, 2000, 63, 920 H Br

Cl O Br

88 Caespitol Cespitol Type: Bisabolane sesquiterpenoids. C15H25Br2ClO2 Crystal (hexane), mp 109–111 °C, [α]D = +4.3° (c = 0.44, CHCl3). Source: Red alga Laurencia caespitosa, sea hare Aplysia dactylomela. Pharm: Toxic (brine shrimp); algicide. Ref: A. G. Gonzalez, et al, Tet. Lett., 1974, 1249; 1976, 3051; 1979, 2719│M. Chang, et al, Phytochemistry, 1989, 28, 1417│M. Wessels, et al, JNP 2000, 63, 920 Br

OH H O Cl Br

89 Curcudiol Type: Bisabolane sesquiterpenoids. C15H24O2 Oil, [α]D = +9.2° (c = 10.8, CHCl3). Source: Gorgonian Pseudopterogorgia rigida (Caribbean Sea). Pharm: Antineoplastic. Ref: M. Ono, et al, Tetrahedron: Asymmetry, 1995, 6, 1829│F. J. Mcenroe, et al, Tetrahedron, 1978, 34, 1661│M. Ono, et al, CPB, 1995, 43, 553 OH

OH

28

2 Sesquiterpenoids

90 (–)-Curcuhydroquinone Curcuquinol Type: Bisabolane sesquiterpenoids. C15H22O2 Viscous oil, [α]D = −21° (c = 0.9, CHCl3). Source: Gorgonians Pseudopterogorgia rigida, Pseudopterogorgia americana and Pseudopterogorgia acerosa. Pharm: Antibacterial (Staphylococcus aureus, Vibrio anguillarum). Ref: F. J. McEnroe, et al, Tetrahedron, 1978, 34, 1661│G. L. Kad, et al, J. Chem. Res. (S), 1999, 164 OH

OH

91 (+)-Curcuhydroquinone Type: Bisabolane sesquiterpenoids. C15H22O2 Source: Gorgonian Pseudopterogorgia rigida. Pharm: Antimicrobial. Ref: F. J. McEnroe, et al, Tetrahedron, 1978, 34, 1661│C. Fuganti, et al, JCS Perkin I, 2000, 3758 OH

OH

92 Curcumene Type: Bisabolane sesquiterpenoids. C15H22 [α]D = −27° (c = 2.1, CHCl3). Source: Gorgonian Pseudopterogorgia rigida (Great Barrier Reef). Pharm: Antibacterial (Staphylococcus aureus, Vibrio anguillarum). Ref: F. J. McEnroe, et al, Tetrahedron, 1978, 34, 1661│C. Fuganti, et al, Synlett, 1998, 1252

93 (+)-Curcuphenol Type: Bisabolane sesquiterpenoids. C15H22O [α]D27 = +26.0° (c = 0.3, CHCl3). Source: Sponge Didiscus flavus gorgonian Pseudopterogorgia rigida (Caribbean Sea). Pharm: Cytotoxic; antibacterial (Staphylococcus aureus and Vibrio anguillarum). Ref: F. J. Mcenroe, et al, Tetrahedron, 1978, 34, 1661│A. E. Wright, et al, JNP, 1987, 50, 976│M. Ono, et al, CPB, 1995, 43, 553│M. Ono, et al, Tetrahedron: Asymmetry, 1995, 6, 1829│T. Suguhara, et al, Tetrahedron: Asymmetry, 1998, 9, 2215│C. Fuganti, et al, Synlett, 1998, 1252│C. Fuganti, et al, JCS Perkin I, 2000, 3758

2.4 Bisabolane Sesquiterpenoids

29

OH

94 Curcuphenol (R)-1,3,5,10-Bisabolatetraen-1-ol Type: Bisabolane sesquiterpenoids. C15H22O Oil, [α]D = −20.9° (c = 1, CHCl3), [α]D = −23.6° (CHCl3). Source: Sponge Myrmeki-oderma dendyi, gorgonian Pseudopterogorgia rigida. Pharm: Antimicrobial. Ref: F. J. McEnroe, et al, Tetrahedron, 1978, 34, 1661│E. Ghisalberti, et al, Aust. J. Chem., 1979, 32, 1627│Y. Letourneux, et al, Heterocycl. Commun., 2005, 11, 291 OH

95 Dehydrocurcuphenol Type: Bisabolane sesquiterpenoids. C15H20O Oil, [α]D23 = −1.2° (c = 0.48, CHCl3). Source: Sponges Epipolasis sp. and Myrmekioderma dendyi. Pharm: H/K-ATPase inhibitor. Ref: N. Fusetani, et al, Experientia, 1987, 43, 1234

HO

96 Deodactol Type: Bisabolane sesquiterpenoids. C15H25Br2ClO2 Cryst. (hexane), mp 134–135 °C, [α]D = +40° (c = 0.2, EtOH). Source: Sea hare Aplysia dactylomela (Bimini Is., The Bahamas, 79 °25’W 25 °42’N). Pharm: Antineoplastic. Ref: K. H. Hollenbeak, et al, Tetrahedron, 1979, 35, 541 Br 8

O

H

OH 5

Cl Br

30

2 Sesquiterpenoids

97 Disydonol A Type: Bisabolane sesquiterpenoids. C30H46O5 Source: Marine-derived fungus Aspergillus sp. from sponge Xestospongia testudinaria (Weizhou I., Guangxi, China). Pharm: Cytotoxic (HTCLs cells). Ref: L. -L. Sun, et al, BoMCL, 2012, 22, 1326

OH OH

OH

O

HO

98 Disydonol C Type: Bisabolane sesquiterpenoids. C30H46O5 Source: Marine-derived fungus Aspergillus sp. from sponge Xestospongia testudinaria (Weizhou I., Guangxi, China). Pharm: Cytotoxic (HTCLs cells). Ref: L. -L. Sun, et al, BoMCL, 2012, 22, 1326 OH HO OH HO OH

99 (−)-5-(Hydroxymethyl)-2-(2′,6′,6′-trimethyltetrahydro-2H-pyran-2-yl)phenol Type: Bisabolane sesquiterpenoids. C15H22O3 White powder; [α]D25 = −2.7° (c = 1.05, CHCl3). Source: Marine-derived fungus Aspergillus sp. from sponge Xestospongia testudinaria (Weizhou coral reef, Giuangxi, China). Pharm: Antibacterial (Staphylococcus albus, MIC = 5.00 μmol/L, control Ciprofloxacin, MIC = 0.312 μmol/L; Bacillus subtilis, MIC = 2.50 μmol/L, Ciprofloxacin, MIC = 1.25 μmol/L; Bacillus cereus, MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.625 μmol/L; Sarcina lutea, MIC > 20 μmol/L, Ciprofloxacin, MIC = 2.50 μmol/L; Escherichia coli, MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.625 μmol/ L; Micrococcus tetragenus, MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.160 μmol/L; Vibrio Parahaemolyticus, MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.312 μmol/L; Vibrio anguillarum, MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.312 μmol/L); cytotoxic (HL60 and A549 cells IC50 > 50 μg/mL, weak). Ref: D. Li, et al, Mar. Drugs, 2012, 10, 234 HO O OH

2.4 Bisabolane Sesquiterpenoids

31

100 (Z)-5-(Hydroxymethyl)-2-(6′-methylhept-2′-en-2′-yl)phenol Type: Bisabolane sesquiterpenoids. C15H22O2 White powder. Source: Marine-derived fungus Aspergillus sp. from sponge Xestospongia testudinaria (Weizhou coral reef, Giuangxi, China). Pharm: Antibacterial (Staphylococcus albus, MIC = 20.0 μmol/L, control Ciprofloxacin, MIC = 0.312 μmol/L; Bacillus subtilis, MIC = 10.0 μmol/L, Ciprofloxacin. MIC = 1.25 μmol/L; Bacillus cereus, MIC = 10.0 μmol/L, Ciprofloxacin, MIC = 0.625 μmol/L; Sarcina lutea, MIC > 20 μmol/L, Ciprofloxacin, MIC = 2.50 μmol/L; Escherichia coli, MIC = 10.0 μmol/L, Ciprofloxacin, MIC = 0.625 μmol/L; Micrococcus tetragenus, MIC = 10.0 μmol/L, Ciprofloxacin, MIC = 0.160 μmol/L; Vibrio Parahaemolyticus, MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.312 μmol/L; Vibrio anguillarum, MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.312 μmol/L); cytotoxic (HL60 and A549 cells, IC50 > 50 μg/mL, weak). Ref: M. W. Sumarah, Phytochemistry 2011, 72, 1833│D. Li, et al, Mar. Drugs, 2012, 10, 234

HO

OH

101 (+)-Methyl sydowate Type: Bisabolane sesquiterpenoids. C16H22O4 Colorless crystals, [α]D25 = +24.7° (CHCl3). Source: Marine-derived fungus Aspergillus sp. from gorgonian Dichotella gemmacea (China waters). Pharm: Antibacterial (Staphylococcus aureus, weak). Ref: M. Y. Wei, et al, Mar. Drugs, 2010, 8, 941 O O O OH

102 3-Oxobolene Type: Bisabolane sesquiterpenoids. C15H20O2 Source: Sponge Myrmekioderma sp. (Phi-Phi I., Thailand). Pharm: Cytotoxic (HT29, potent). Ref: A. Yegdaneh, et al, Nat. Prod. Commun., 2013, 8, 1355 OH

O

32

2 Sesquiterpenoids

103 1-Oxocurcuphenol Type: Bisabolane sesquiterpenoids. C15H20O2 Source: Sponge Myrmekioderma sp. (Phi-Phi I., Thailand). Pharm: Cytotoxic (HT29, potent). Ref: A. Yegdaneh, et al, Nat. Prod. Commun., 2013, 8, 1355 OH O H

104 Parahigginic acid Type: Bisabolane sesquiterpenoids. C16H20O4 Oil, [α]D = −29.2° (c = 0.15, CHCl3). Source: Sponge Parahigginsia sp. (Taiwan waters). Pharm: Cytotoxic (P388, IC50 = 1.0 μg/mL, control (+)-Curcuphenol, IC50 = 0.1 μg/mL; KB16, IC50 = 4.8 μg/ mL, (+)-Curcuphenol, IC50 = 8.3 μg/mL; A549, IC50 = 3.9 μg/mL; HT29, IC50 = 6.0 μg/ mL, (+)-Curcuphenol, IC50 = 8.1 μg/mL). Ref: C. -Y. Chen, et al, JNP, 1999, 62, 573│Y. -C. Shen, et al, J. Chin, Chem. Soc., 1999, 46, 201

O HO HO

O

105 Parahigginin Type: Bisabolane sesquiterpenoids. C15H22O3 [α]D = +4.5° (c = 0.325, CHCl3). Source: Sponge Parahigginsia sp. (Taiwan waters). Pharm: Cytotoxic (in vitro, P388, IC50 = 2.8 μg/mL, KB16, IC50 = 5.7 μg/mL, A549, IC50 = 2.8 μg/mL, HT29, IC50 = 5.4 μg/mL). Ref: Y. -C. Shen, et al, J. Chin, Chem. Soc., 1999, 46, 201 OH

HO

H

O

106 Parahigginol B Type: Bisabolane sesquiterpenoids. C17H24O4 Oil, [α]D = −11.4° (c = 0.58, CHCl3). Source: Sponge Parahigginsia sp. (Taiwan waters). Pharm: Cytotoxic (P388, IC50 = 3.0 μg/mL, control (+)-Curcuphenol, IC50 = 0.1 μg/mL; KB16, IC50 = 4.9 μg/ mL, (+)-Curcuphenol, IC50 = 8.3 μg/mL; A549, IC50 = 10 μg/mL; HT29, IC50 = 3.5 μg/ mL, (+)-Curcuphenol, IC50 = 8.1 μg/mL). Ref: C. -Y. Chen, et al, JNP, 1999, 62, 573│Y. -C. Shen, et al, J. Chin, Chem. Soc., 1999, 46, 201

2.4 Bisabolane Sesquiterpenoids

33

O

HO

O

H

O

107 Parahigginol C Type: Bisabolane sesquiterpenoids. C17H26O3 Oil, [α]D = −9.5° (c = 2.1, CHCl3). Source: Sponge Parahigginsia sp. (Taiwan waters). Pharm: Cytotoxic (P388, IC50 = 2.5 μg/mL, control (+)-Curcuphenol, IC50 = 0.1 μg/mL; KB16, IC50 = 3.9 μg/ mL, (+)-Curcuphenol, IC50 = 8.3 μg/mL; A549, IC50 = 2.8 μg/mL; HT29, IC50 = 2.6 μg/ mL, (+)-Curcuphenol, IC50 = 8.1 μg/mL). Ref: C. -Y. Chen, et al, JNP, 1999, 62, 573│Y. -C. Shen, et al, J. Chin, Chem. Soc., 1999, 46, 201

O

HO

O

108 Parahigginol D Type: Bisabolane sesquiterpenoids. C15H18O3 Oil, [α]D = −73.5° (c = 0.225, CHCl3). Source: Sponge Parahigginsia sp. (Taiwan waters). Pharm: Cytotoxic (P388, IC50 = 2.9 μg/mL, control (+)-Curcuphenol, IC50 = 0.1 μg/mL; KB16, IC50 = 7.2 μg/mL, (+)-Curcuphenol, IC50 = 8.3 μg/mL; A549, IC50 = 3.8 μg/mL; HT29, IC50 = 3.3 μg/mL, (+)-Curcuphenol, IC50 = 8.1 μg/mL). Ref: C. -Y. Chen, et al, JNP, 1999, 62, 573│Y. -C. Shen, et al, J. Chin, Chem. Soc., 1999, 46, 201

HO HO H

O

109 Parahigginone Type: Bisabolane sesquiterpenoids. C15H20O2 [α]D = +75.0° (c = 0.38, CHCl3). Source: Sponge Parahigginsia sp. (Taiwan waters). Pharm: Cytotoxic (in vitro, P388, IC50 = 1.3 μg/mL, KB16, IC50 = 2.5 μg/mL, A549, IC50 > 50 μg/mL, HT29, IC50 = 37 μg/ mL). Ref: Y. -C. Shen, et al, J. Chin, Chem. Soc., 1999, 46, 201

34

2 Sesquiterpenoids

HO

O

110 (–)-Sydonic acid Type: Bisabolane sesquiterpenoids. C15H22O4 White powder; [α]D25 = –2.0° (c=1.03, CHCl3). Source: Marine-derived fungus Aspergillus sp. from sponge Xestospongia testudinaria (Weizhou coral reef, Giuangxi, China). Pharm: Antibacterial (Staphylococcus albus, MIC > 20 μmol/L, control Ciprofloxacin, MIC=0.312 μmol/L; Bacillus subtilis, MIC=2.50 μmol/L, Ciprofloxacin, MIC=1.25 μmol/L; Bacillus cereus, MIC > 20 μmol/L, Ciprofloxacin, MIC=0.625 μmol/L; Sarcina lutea, MIC=2.50 μmol/L, Ciprofloxacin, MIC=2.50 μmol/L; Escherichia coli, MIC=5.00 μmol/L, Ciprofloxacin, MIC=0.625 μmol/ L; Micrococcus tetragenus, MIC=20.0 μmol/L, Ciprofloxacin, MIC=0.160 μmol/L; Vibrio Parahaemolyticus, MIC=10.0 μmol/L, Ciprofloxacin, MIC=0.312 μmol/L; Vibrio anguillarum, MIC=5.00 μmol/L, Ciprofloxacin, MIC=0.312 μmol/L); cytotoxic (HL60 and A549 cells, IC50 > 50 μg/mL, weak). Ref: D. Li, et al, Mar. Drugs, 2012, 10, 234 O HO

OH

OH

111 (+)-Sydonic acid Type: Bisabolane sesquiterpenoids. C15H22O4 Needles (C6H6), mp 85–86 °C, [α]D20= +2.73° (c=2.3, MeOH). Source: Marine-derived fungus Aspergillus sp. from gorgonian Dichotella gemmacea (China waters). Pharm: Antibacterial (Staphylococcus aureus, weak). Ref: M. Y. Wei, et al, Mar. Drugs, 2010, 8, 941 HO

OH

OH O

112 (–)-Sydonol Type: Bisabolane sesquiterpenoids. C15H24O3 White powder; [α]D25 = −3.6° (c = 3.70, CHCl3). Source: Marine-derived fungus Aspergillus sp. from sponge Xestospongia testudinaria (Weizhou coral reef, Giuangxi, China). Pharm: Antibacterial (Staphylococcus albus, MIC = 5.00 μmol/L, control Ciprofloxacin, MIC = 0.312 μmol/L; Bacillus subtilis, MIC > 20 μmol/L, Ciprofloxacin, MIC = 1.25 μmol/L; Bacillus cereus,

2.5 Elemane Sesquiterpenoids

35

MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.625 μmol/L; Sarcina lutea, MIC > 20 μmol/L, Ciprofloxacin, MIC = 2.50 μmol/L; Escherichia coli, MIC = 20.0 μmol/L, Ciprofloxacin, MIC = 0.625 μmol/L; Micrococcus tetragenus, MIC = 1.25 μmol/L, Ciprofloxacin, MIC = 0.160 μmol/L; Vibrio Parahaemolyticus, MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.312 μmol/L; Vibrio anguillarum, MIC > 20 μmol/L, Ciprofloxacin, MIC = 0.312 μmol/L); cytotoxic (HL60 and A549 cells IC50 > 50 μg/mL, weak). Ref: D. Li, et al, Mar. Drugs, 2012, 10, 234 HO

OH

OH

113 (+)-Sydowic acid Type: Bisabolane sesquiterpenoids. C15H20O4 Source: Marine-derived fungus Aspergillus sp. from gorgonian Dichotella gemmacea (China waters). Pharm: Antibacterial (Staphylococcus aureus, weak). Ref: M. Y. Wei, et al, Mar. Drugs, 2010, 8, 941 OH O O OH

2.5 Elemane Sesquiterpenoids 114 6-O-(4-Hydroxy-4-methyl-2E-pentenoyl)-6-hydroxy-13-nor1,3-elemadien-11-one Type: Elemane sesquiterpenoids. C20H30O4 Oil, [α]D25 = +12.3° (c = 1, CHCl3). Source: Annelida Eunicea sp. (Caribbean Sea). Pharm: Antituberculosis (Mycobacterium tuberculosis H37Rv, 6.25 μg/mL, significant inhibitory activity). Ref: S. P. Garzón, et al, JNP, 2005, 68, 1354 1 6

O

O

O

OH

36

2 Sesquiterpenoids

2.6 Germacrane Sesquiterpenoids 115 (+)-Germacrene D Type: Simple germacrane sesquiterpenoids. C15H24 Oil, [α]D22 = +190° (c = 1, CHCl3). Source: Annelida Eunicea fusca (Santa Marta Bay, Caribbean Sea, Colombia) and gorgonian Pseudopterogorgia americana, soft coral Sinularia mayi, liverworts Preissia quadrata and Jackiella javanica. Pharm: Anti-inflammatory (TPA-induced mouse ear edema, 0.5 mg/ear, InRt = 7.1%, control Indomethacin, InRt = 77.3%); antifoulant. Ref: W. R. Chan, et al, Tetrahedron, 1990, 46, 1499│E. Reina, et al, BoMCL, 2011, 21, 5888

116 1-Hydroxy-4,10(14)-germacradien-12,6-olide Type: 12,6-Germacranolide sesquiterpenoids. C15H22O3 Oil, [α]D25 = +24.6° (c = 1.1, CHCl3). Source: Annelida Eunicea sp. (Caribbean Sea). Pharm: Antiplasmodial (malarial parasite CRPF W2, IC50 = 18 μg/mL); cytotoxic (CCRF-CEM, IC50 = 31.3 μg/mL; HL60, IC50 = 51.5 μg/mL; Molt4, IC50 = 19.6 μg/mL; RPMI8226, IC50 = 90.4 μg/mL; MCF7; IC50 = 82.2 μg/mL; inhibits growth of human cancer cells weakly). Ref: S. P. Garzón, et al, JNP, 2005, 68, 1354 OH 1 6

H 11

O O

117 Menelloide D Type: 12,6-Germacranolide sesquiterpenoids. C15H20O3 Colorless oil, [α]D25 = −36° (c = 0.05, CHCl3). Source: Annelida Menella sp. (depth of 100 m, Southern Taiwan). Pharm: Elastase inhibitor (release of elastase by hmn neutrophils, 10 μg/mL, InRt = 10.5%). Ref: S. -Y. Kao, et al, Tetrahedron, 2011, 67, 7311│S. -Y. Kao, et al, Mar. Drugs, 2011, 9, 1534│S. -Y. Kao, et al, CPB, 2011, 59, 1048

O O

O

2.6 Germacrane Sesquiterpenoids

37

118 Furanodiene Isofuranodiene Type: Furanogermacrane sesquiterpenoids. C15H20O Cryst., mp 66 °C. Source: Soft corals Cespitularia sp. and Efflatounaria sp., gorgonians Pacifigorgia pulchraexilis, Pacifigorgia media and Pseudopterogorgia sp. Pharm: Antibacterial (grampositive bacteria). Ref: B. F. Bowden, et al, Aust. J. Chem., 1980, 33, 927│R. R. Izac, et al, Tet. Lett., 1982, 23, 3743│R. R. Izac, et al, Tetrahedron, 1982, 38, 301│W. R. Chan, et al, Tetrahedron, 1990, 46, 1499│M. G. Phan, et al, Tap Chi Hoa Hoc, 2000, 38, 91 O

O

O

OH O

O

119 6-O-(4-Hydroxy-4-methyl-2E-pentenoyl)-1,6-dihydroxy-13-nor4,10(14)-germacradien-11-one Type: Nor- seco- and homogermacrane sesquiterpenoids. C20H30O5 Oil, [α]D25 = +77.6° (c = 1.2, CHCl3). Source: Annelida Eunicea sp. (Caribbean Sea). Pharm: Antiplasmo-dial (malarial parasite CRPF W2, IC50 = 14 μg/mL). Ref: S. P. Garzón, et al, JNP, 2005, 68, 1354 OH 1 6

O

O

O

OH

120 6-O-(4-Hydroxy-4-methyl-2E-pentenoyl)-6-hydroxy-1-oxo-13-nor-4,10(14)germacradien-11-one Type: Nor- seco- and homogermacrane sesquiterpenoids. C20H28O5 Oil, [α]D25 = +12.3° (c = 1.0, CHCl3). Source: Annelida Eunicea sp. (Caribbean Sea). Pharm: Antiplasmo-dial (malarial parasite CRPF W2, IC50 = 16 μg/mL); antituberculosis (Mycobacterium tuberculosis H37Rv, 6.25 μg/mL, significant inhibitory activity). Ref: S. P. Garzón, et al, JNP, 2005, 68, 1354

38

2 Sesquiterpenoids

O 1 6

O

O

O

OH

121 (–)-Anthoplalone Type: Lepidozanes and bicyclogermacrane sesquiterpenoids. C16H26O2 Pale yellow oil, [α]D = −4.4° (c = 0.09, CHCl3). Source: Sea anemone Anthopleura pacifica. Pharm: Cytotoxic (B16 cells, IC50 = 22 μg/mL). Ref: G. -C. Zheng, et al, Tet. Lett., 1990, 31, 2617│S. Hanessian, et al, JOC, 1999, 64, 4893

O

O

2.7 Miscellaneous Monocyclic Sesquiterpenoids 122 Chabranol Type: Miscellaneous monocyclic sesquiterpenoids. C14H24O3 Oil, [α]D25 = −56° (c = 0.1, CHCl3). Source: Soft coral Nephthea chabroli (Siaoliouciou I., Taiwan). Pharm: Cytotoxic (P388 cells, ED50 = 1.81 μg/mL, A549, ED50 > 50 μg/mL, HT29, ED50 > 50 μg/mL). Ref: S. Y. Cheng, et al, Org. Lett., 2009, 11, 4830│X. Wang, et al, JOC, 2010, 75, 5392 H

O

O

OH

2.8 Caryophyllane Sesquiterpenoids 123 Rumphellaone A Type: Caryophyllane sesquiterpenoids. C15H24O3 Colorless oil, [α]D25 = +257° (c = 0.014, CHCl3). Source: Gorgonian Rumphella antipathies. Pharm: Cytotoxic

2.9 Cuparane Sesquiterpenoids

39

(CCRF-CEM hmn T-cell acute lymphoblastic leukemia tumor cell CCRF-CEM, IC50 = 12.6 μg/mL, modest). Ref: H. -M. Chung, et al, Tet. Lett., 2010, 51, 6025 O

H

O O

H

2.9 Cuparane Sesquiterpenoids 124 Cupalaurenol 4-Bromo-2-methyl-5-(1,2,2-trimethyl-3-cyclopenten-1-yl)phenol Type: Cuparane sesquiterpenoids. C15H19BrO Oil, [α]D19 = +87.9° (c = 1, CHCl3). Source: Red alga Laurencia sp. (N. Borneo I., Sabah, Malaysia), sea hare Aplysia dactylomela. Pharm: Antibacterial (30 mg/disc: Staphylococcus aureus, IZD = 15 mm, MIC = 125 μg/mL; Staphylococcus sp., IZD = 15 mm, MIC = 125 μg/mL; Salmonella sp., IZD = 15 mm, MIC = 125 μg/mL; Vibrio cholera, IZD = 11 mm, MIC = 200 μg/mL); ichthyotoxic; antifungal. Ref: C. S. Vairappan, et al, Mar. Drugs, 2010, 8, 1743│T. Ichiba, et al, JOC, 1986, 51, 3364 HO

Br

125 Cupalaurenol acetate Type: Cuparane sesquiterpenoids. C17H21BrO2 Oil, [α]D19 = +65.1° (c = 1, CHCl3). Source: Sea hare Aplysia dactylomela. Pharm: Ichthyotoxic; antimicrobial; antifungal. Ref: T. Ichiba, et al, JOC, 1986, 51, 3364

O

O

Br

40

2 Sesquiterpenoids

2.10 Laurane Sesquiterpenoids 126 7-Hydroxylaurene Type: Laurane sesquiterpenoids. C15H20O [α]D20 = +45° (c = 2.5, CHCl3). Source: Red alga Laurencia sp. Pharm: Antibiotic (strong). Ref: S. J. Wratten, et al, JOC, 1977, 42, 3343

7

OH

127 allo-Laurinterol 7-Hydroxy-10-bromo-laurene Type: Laurane sesquiterpenoids. C15H19BrO Pale yellow viscous oil, [α]D = +22° (c = 1.7, CHCl3). Source: Red algae Laurencia obtusa (Dominica) and Laurencia sp. Pharm: Antimicrobial. Ref: G. M. König, et al, PM, 1997, 63, 186│R. Kazlauskas, et al, Aust. J. Chem., 1976, 29, 2533│D. J. Faulkner, Tetrahedron, 1977, 33, 1421 Br

10

5 7

OH

128 allo-Laurinterol acetate Type: Laurane sesquiterpenoids. C17H21BrO2 Glass, [α]D20 = +47° (c = 0.07, MeOH). Source: Sea hare Aplysia dactylomela (shallow waters, near La Parguera, Puerto Rico). Pharm: Cytotoxic (PS cells (= P388), ED50 = 40 μg/mL). Ref: F. J. Schmitz, et al, JACS, 1982, 104, 6415 Br

O

O

129 Cyclolaurene 1,2-Dimethyl-2-(4-methylphenyl)bicyclo[3.1.0]hexane Type: Cyclolaurane sesquiterpenoids. C15H20 Oil, [α]D = −9.0° (c = 0.22, CHCl3). Source: Red algae Laurencia spp., sea hares Aplysia dactylomela and Aplysia spp. Pharm: Ichthyotoxic; antimicrobial; antifungal. Ref: T. Ichiba, et al, JOC, 1986, 51, 3364│S. Takano, et al, Tet. Lett., 1992, 33, 329│A. Nath, et al, JOC, 1992, 57, 1467│A. Srikrishna, et al, Tetrahedron, 1992, 48, 3429

2.10 Laurane Sesquiterpenoids

41

130 Cyclolaurenol Type: Cyclolaurane sesquiterpenoids. C15H19BrO Cryst., mp 109–109.5 °C, [α]D21 = −9.3° (c = 4.04, CHCl3). Source: Sea hare Aplysia dactylomela. Pharm: Ichthyotoxic. Ref: T. Ichiba, et al, JOC, 1986, 51, 3364 HO

Br

131 Cyclolaurenol acetate Type: Cyclolaurane sesquiterpenoids. C17H21BrO2 Oil, [α]D19 = −9.2° (c = 0.82, CHCl3). Source: Sea hare Aplysia dactylomela. Pharm: Ichthyotoxic. Ref: T. Ichiba, et al, JOC, 1986, 51, 3364 O

O

Br

132 Debromolaurinterol Type: Cyclolaurane sesquiterpenoids. C15H20O [α]D20 = −12.2° (CHCl3). Source: Red algae Laurencia intermedia, Laurencia okamurai and Laurencia johnstonii. Pharm: Antimycobacterial (weak). Ref: Z. Kuwano, et al, J. Appl. Phycol., 1998, 10, 9│G. M. Koenig, et al, PM, 2000, 66, 337│Y. Okamoto, et al, Biosci., Biotechnol., Biochem., 2001, 65, 474

10 7 8

OH

133 Laurinterol Type: Cyclolaurane sesquiterpenoids. C15H19BrO Cryst. (MeOH), mp 54–55 °C, [α]D = +13.3° (c = 1.9, CHCl3). Source: Red algae Laurencia intermedia, Laurencia okamurai, Laurencia nidifica, Marginiosporum aberrans, Amphiroa nidifica, Corallina pilulifera, Corallina chilensis and Rhodomela californica, sea hare Aplysia sp. Pharm: Reverse transcriptase inhibitor; antibiotic (very effective). Ref: A. F. Cameron, et al, JCS (B), 1969, 692│T. Irie, et al, Tetrahedron, 1970, 26,

42

2 Sesquiterpenoids

3271│Y. Shizuri, et al, Phytochemistry, 1984, 23, 2672│Y. Okamoto, et al, Biosci., Biotechnol., Biochem., 2001, 65, 474 Br

10 7

OH

8

2.11 Trichothecane Sesquiterpenoids 134 4-O-Acetylverrol Verrol 4-acetate Type: Trichothecane sesquiterpenoids. C23H32O7 [α]D20 = −30° (c = 0.1, MeOH). Source: Marine-derived fungus Acremonium neo-caledoniae from driftwood sample (New Caledonia). Pharm: Cytotoxic (KB cells, IC50 = 400 ng/mL). Ref: D. Laurent, et al, PM, 2000, 66, 63 H

O

H O

O

CH2 O

O

O OH

135 12,13-Deoxyroridin E Type: Trichothecane sesquiterpenoids. C29H38O7 [α]D = −204° (c = 0.025, CHCl3). Source: Marine-derived fungus Myrothecium roridum (submerged woody sample, Palau, Oceania). Pharm: Cytotoxic (HL60, IC50 = 25 ng/mL, L1210, IC50 = 15 ng/mL). Ref: M. Namikoshi, et al, JNP, 2001, 64, 396│M. Saleem, et al, NPR, 2007, 24, 1142 (rev) H

O

H O

O

O

O O HO

H

2.11 Trichothecane Sesquiterpenoids

43

136 2′,3′-Deoxyroritoxin D Type: Trichothecane sesquiterpenoids. C29H32O10 Powder. Source: Marine-derived fungus Myrothecium roridum TUF 98F42 (wood sample, Palau, Oceania). Pharm: Cytotoxic (L1210, IC50 = 0.45 μmol/L). Ref: J. Z. Xu, et al, J. Antibiot., 2006, 59, 451 H

O

H

9 10 7

O

O

O

O O 3'

2'

O

7' 8'

H O

14'

OH

O

137 12′-Hydroxyroridin E Type: Trichothecane sesquiterpenoids. C29H38O9 Powder, [α]D25 = +4.8° (c = 4, MeOH). Source: Marine-derived fungus Myrothecium roridum TUF 98F42 (wood sample, Palau, Oceania). Pharm: Cytotoxic (L1210, IC50 = 0.19 μmol/L). Ref: J. Z. Xu, et al, J. Antibiot., 2006, 59, 451 16

10

9

H

O

H

7

O O O

O 2'

O 12'

OH O

8' 6'

H HO

13'

138 Roridin Q Type: Trichothecane sesquiterpenoids. C35H46O11 Powder, [α]D25 = +2.4° (c = 0.4, MeOH). Source: Marine-derived fungus Myrothecium roridum TUF 98F42 (wood sample, Palau, Oceania). Pharm: Cytotoxic (L1210, IC50 = 31.2 μmol/L). Ref: J. Z. Xu, et al, J. Antibiot., 2006, 59, 451

44

2 Sesquiterpenoids

H

10

9

16

O

H

7

O O O

O

O 12'

2'

OH O

8' 6'

H O

O

13'

OH

139 Roridin R 2′,3′-Dihydro-2′-hydroxyroridin H Type: Trichothecane sesquiterpenoids. C29H38O9 Powder, [α]D25 = +9.6° (c = 0.05, CHCl3). Source: Marine-derived fungus Myrothecium sp. TUF 98F2 from an unidentified sponge (Indonesia). Pharm: Antifungal (Saccharomyces cerevisiae, MIA = 1 μg/disc). Ref: J. Z. Xu, et al, J. Antibiot., 2006, 59, 451 9

H

10

O

H O

O O

O

O 2'

HO

O 3'

O

140 Verrucarin A Muconomycin A Type: Trichothecane sesquiterpenoids. C27H34O9 Cryst., mp 330 °C, [α]D = +208° (dioxan), [α]D = +260° (CHCl3). Source: Marine-derived fungus Acremonium neo-caledoniae from driftwood sample. Pharm: Protein synthesis inhibitor (fungi); antineoplastic; insecticide. Ref: D. Laurent, et al, PM, 2000, 66, 63

2.12 Eudesmane Sesquiterpenoids

H

O

H O

CH2

O

O

O

O

HO

45

O H

O

2.12 Eudesmane Sesquiterpenoids 141 Ainigmaptilone A (4α,5β,10α)-14-Hydroxy-1,11-eudesmadien-3-one Type: Simple eudesmane sesquiterpenoids. C15H22O2 Oil, [α]D25 = +26.8° (c = 0.23, CHCl3). Source: Gorgonian Ainigmaptilon antarcticus (psychrophilic, cold water, Eastern Weddell Sea, Western Antarctica). Pharm: Defensive metabolite (antibiotic, inhibits predation by local predatory sea star Odontaster validus). Ref: K. B. Iken, et al, JNP, 2003, 66, 888│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) H

O

2

OH

142 Brasudol (1β,7β)-1-Bromo-4(15)-eudesmen-11-ol Type: Simple eudesmane sesquiterpenoids. C15H25BrO mp 105–106 °C, [α]D26 = +16.5°. Source: Sea hare Aplysia brasiliana (Florida). Pharm: Antifeedant (fish). Ref: R. K. Dieter, et al, Tet. Lett., 1979, 1645 Br

H

OH

143 2-Bromo-11-eudesmen-5-ol Type: Simple eudesmane sesquiterpenoids. C15H25BrO Source: Green alga Neomeris annulata (Kwajalein Atoll and Guam). Pharm: Antifeedant (fish). Ref: V. J. Paul, et al, J. Chem. Ecol., 1993, 19, 1847│K. D. Meyer, et al, Mar. Biol. (Berlin), 1995, 122, 537

46

2 Sesquiterpenoids

Br

OH

144 3-Bromo-11-eudesmen-5-ol Type: Simple eudesmane sesquiterpenoids. C15H25BrO Source: Green alga Neomeris annulata (Kwajalein Atoll and Guam). Pharm: Antifeedant (fish). Ref: V. J. Paul, et al, J. Chem. Ecol., 1993, 19, 1847│K. D. Meyer, et al, Mar. Biol. (Berlin), 1995, 122,

Br

OH

145 Isobrasudol (1β,7α)-1-Bromo-4(15)-eudesmen-11-ol Type: Simple eudesmane sesquiterpenoids. C15H25BrO mp 105–107 °C, [α]D26 = +10.3°. Source: Sea hare Aplysia brasiliana (Florida). Pharm: Ichthyotoxin; antifeedant. Ref: R. K. Dieter, et al, Tet. Lett., 1979, 1645 Br

H

OH

146 Junceol A‡ Type: Simple eudesmane sesquiterpenoids. C17H28O3 Oil, [α]D26 = −1° (c = 0.1, CHCl3). Source: Sea pen Virgularia juncea. Pharm: Cytotoxic (P388, ED50 = 5.1 μg/ mL). Ref: S. P. Chen, et al, JNP, 2001, 64, 1241 OH

O O

147 Kandenol A Type: Simple eudesmane sesquiterpenoids. C15H24O3 Source: Mangrove-derived streptomycete Streptomyces sp. (endophytic) from mangrove Kandelia candel (stem, Xiamen, Fujian, China). Pharm: Antibacterial (Bacillus subtilis and Mycobacterium vaccae, weak). Ref: L. Ding, et al, JNP, 2012, 75, 2223

2.12 Eudesmane Sesquiterpenoids

O

47

OH

H

OH

148 Kandenol B Type: Simple eudesmane sesquiterpenoids. C15H24O4 Source: Mangrove-derived streptomycete Streptomyces sp. (endophytic) from mangrove Kandelia candel (stem, Xiamen, Fujian, China). Pharm: Antibacterial (Bacillus subtilis and Mycobacterium vaccae, weak). Ref: L. Ding, et al, JNP, 2012, 75, 2223 O

OH

OH

OH

149 Kandenol C Type: Simple eudesmane sesquiterpenoids. C15H24O5 Source: Mangrove-derived streptomycete Streptomyces sp. (endophytic) from mangrove Kandelia candel (stem, Xiamen, Fujian, China). Pharm: Antibacterial (Bacillus subtilis and Mycobacterium vaccae, weak). Ref: L. Ding, et al, JNP, 2012, 75, 2223 O

OH

O

OH

OH

150 Kandenol D Type: Simple eudesmane sesquiterpenoids. C15H24O4 Source: Mangrove-derived streptomycete Streptomyces sp. (endophytic) from mangrove Kandelia candel (stem, Xiamen, Fujian, China). Pharm: Antibacterial (Bacillus subtilis and Mycobacterium vaccae, weak). Ref: L. Ding, et al, JNP, 2012, 75, 2223 O

O

OH

OH

151 Kandenol E Type: Simple eudesmane sesquiterpenoids. C15H22O3 Source: Mangrove-derived streptomycete Streptomyces sp. (endophytic) from mangrove Kandelia candel (stem,

48

2 Sesquiterpenoids

Xiamen, Fujian, China). Pharm: Antibacterial (Bacillus subtilis and Mycobacterium vaccae, weak). Ref: L. Ding, et al, JNP, 2012, 75, 2223 O

OH

O

152 1-Hydroxy-4-eudesmaen-12,6-olide Type: 12,6-Eudesmanolide sesquiterpenoids C15H22O3 Oil, [α]D25 = +25.8° (c = 1.1, CHCl3). Source: Annelida Eunicea sp. (Caribbean Sea). Pharm: Antiplasmodial (malarial parasite CRPF W2, IC50 = 14 μg/mL); antituberculosis (Mycobacterium tuberculosis H37Rv, 6.25 μg/mL, significant inhibitory activity). Ref: S. P. Garzón, et al, JNP, 2005, 68, 1354 OH 1 6

O O

153 Atractylon Type: Furanoeudesmane sesquiterpenoids. C15H20O Cryst., mp 38 °C, [α]D = +40° (c = 10, CHCl3). Source: Soft coral Cespitularia sp. Pharm: 5-Lipoxygenase inhibitor. Ref: B. F. Bowden, et al, Aust. J. Chem., 1980, 33, 927 O

H

154 Furanoeudesm-3-ene 8,12-Epoxy-3,7,11-eudesmatriene Type: Furanoeudesmane sesquiterpenoids. C15H20O Amorph. powder, [α]D = +70.2° (c = 0.5, hexane). Source: Gorgonian Dasyste-nella acanthina (psychrophilic, cold water, Antarctic). Pharm: Toxic (mosquito fish Gambusia affinis ichthyotoxicity assay, 10 ppm, defensive metabolite). Ref: M. Gavagnin, et al, JNP, 2003, 66, 1517│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) O

H

2.12 Eudesmane Sesquiterpenoids

49

155 Tubipofuran Type: Furanoeudesmane sesquiterpenoids. C15H18O Oil, [α]D = +5.7° (c = 0.6, CHCl3). Source: Stolonifer Tubipora musica (Japan waters). Pharm: Cytotoxic; ichthyotoxic. Ref: K. Iguchi, et al, Chem. Lett., 1986, 1789│A. Ojida, et al, JOC, 1994, 59, 5970 H

O

156 Tubipolide B Type: 12,8-Eudesmanolides sesquiterpenoids. C15H18O2 Oil, [α]D25 = −51.6° (c = 0.02, CHCl3). Source: Stolonifer Tubipora musica (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 3.69 μg/mL). Ref: C. Y. Duh, et al, JNP, 2001, 64, 1430 H O O H

157 Tubipolide G Type: 12,8-Eudesmanolides sesquiterpenoids. C17H18O4 Oil, [α]D25 = +22.6° (c = 0.02, CHCl3). Source: Stolonifer Tubipora musica (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 4.01 μg/mL). Ref: C. Y. Duh, et al, JNP, 2001, 64, 1430 O O O

H O

158 6-O-(4-Hydroxy-4-methyl-2E-pentenoyl)-1,6-dihydroxy-13-nor-4(15)eudesmen-11-one Type: Noreudesmane sesquiterpenoids. C20H30O5 Oil, [α]D25 = +32° (c = 1.1, CHCl3). Source: Annelida Eunicea sp. (Caribbean Sea). Pharm: Antiplasmodial (malarial parasite CRPF W2, IC50 = 10 μg/mL); antituberculosis (Mycobacterium tuberculosis H37Rv, 6.25 μg/mL, significant inhibitory activity). Ref: S. P. Garzón, et al, JNP, 2005, 68, 1354

50

2 Sesquiterpenoids

OH 1 6

H

O

O

O

OH

159 Cycloeudesmol Isocycloeudesmol Type: Cycloeudesmane sesquiterpenoids. C15H26O Cryst. (hexane/ isopropyl ether), mp 99.5–100.5 °C, [α]D = +21.5° (c = 2.1, CHCl3). Source: Red algae Laurencia nipponica and Chondria oppositiclada. Pharm: Antibiotic. Ref: T. Suzuki, et al, Chem. Lett., 1980, 1267│T. Suzuki, et al, Tet. Lett., 1981, 22, 3423│E. Y. Chen, JOC, 1984, 49, 3245│M. Ando, et al, Tet. Lett., 1985, 26, 235

OH

160 Heterogorgiolide Type: Cycloeudesmane sesquiterpenoids. C16H20O3 Amorph. solid, mp 149–151 °C, [α]D25 = +116° (c = 1.0, CHCl3). Source: Gorgonian Heterogorgia uatumani (Brazil). Pharm: Predator deterrent. Ref: L, F. Maia, et al, JNP, 1999, 62, 1322 O O

9

O

H

161 Spirotubipolide Type: Rearranged eudesmane sesquiterpenoids. C17H20O5 Cryst., [α]D = −194° (c = 0.3, CHCl3). Source: Stolonifer Tubipora musica (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 3.24 μg/mL). Ref: K. Iguchi, et al, CPB, 1987, 35, 3531│C. Y. Duh, et al, JNP, 2001, 64, 1430 O O O

H O

O

2.13 Eremophilane Sesquiterpenoids

51

2.13 Eremophilane Sesquiterpenoids 162 3-Acetoxy-9,7(11)-dien-7α-hydroxy-8-oxoeremophilane Type: Simple eremophilane sesquiterpenoids. C17H24O4 Needles (CHCl3), [α]D20 = +3° (c = 0.2, MeOH). Source: Marine-derived fungus Penicillium sp. BL27-2 (sea mud, Bering Sea). Pharm: Cytotoxic (three different cells, less active by several orders of magnitude than 3-Acetyl-13-deoxyphomenone). Ref: Y. F. Huang, et al, Chin. Chem. Lett., 2008, 19, 562 O

O

1

9

3

6

7

O

11

OH

163 Antibiotic JBIR 28 Type: Simple eremophilane sesquiterpenoids. C15H20O4 Amorph. powder, mp 120 °C, [α]D25 = +188.7° (c = 0.2, MeOH). Source: Marine-derived fungus Penicillium sp. from ascidian Didemnum molle (Japan waters). Pharm: Cytotoxic (HeLa cells, moderate). Ref: K. Motohashi, et al, J. Antibiot., 2009, 62, 247 O

HO OH

O

164 Chloroacetoxyhydroxyeremophiltrienone Type: Simple eremophilane sesquiterpenoids. C14H15ClO4 Colorless oil; [α]D20 = +274° (c = 0.05, CHCl3). Source: Deep-sea fungus Penicillium sp. PR19 N-1 (Antarctic Ocean). Pharm: Cytotoxic (HL60, IC50 = 11.8 μmol/L, A549, IC50 = 12.2 μmol/L). Ref: G. Wu, et al, Mar. Drugs, 2013, 11, 1399 Cl O

O O

OH

165 DehydroxymethoxyeremofortineC Type: Simple eremophilane sesquiterpenoids. C18H24O6 Colorless oil, [α]D20 = +119° (c = 0.16, CHCl3). Source: Deep-sea fungus Penicillium sp. PR19 N-1 (Antarctic Ocean). Pharm: Cytotoxic (HL60, IC50 = 28.3 μmol/L, A549, IC50 = 5.2 μmol/L). Ref: A. Lin, et al, Arch. Pharm. Res., 2014, 37, 839

52

2 Sesquiterpenoids

O

O O

O O

O

166 13-Deoxyphomenone Type: Simple eremophilane sesquiterpenoids. C15H20O3 Cryst., mp 104–105 °C, [α]D20 = +236° (c = 0.5, MeOH). Source: Marine-derived fungus Penicillium sp. from ascidian Didemnum molle (Japan waters). Pharm: Cytotoxic (HeLa cells, moderate). Ref: Y. Tirilly, et al, Phytochemistry, 1983, 22, 2082 O HO

O

167 EremofortineCa Type: Simple eremophilane sesquiterpenoids. C17H22O6 Source: Deep-sea fungus Penicillium sp. PR19 N-1 (Antarctic Ocean). Pharm: Cytotoxic (HL60 and A549). Ref: G. Wu, et al, Mar. Drugs, 2013, 11, 1399 O

O

O O

OH

O

168 EremofortineCb Type: Simple eremophilane sesquiterpenoids. C17H22O6 Source: Deep-sea fungus Penicillium sp. PR19 N-1 (Antarctic Ocean). Pharm: Cytotoxic (HL60 and A549). Ref: G. Wu, et al, Mar. Drugs, 2013, 11, 1399 O

OH O

O O

O

169 Eremophildiendiol Type: Simple eremophilane sesquiterpenoids. C15H24O2 Colorless oil, [α]D20 = −49° (c = 0.05, CHCl3). Source: Deep-sea fungus Penicillium sp. PR19 N-1 (Antarctic Ocean). Pharm: Cytotoxic (HL60, IC50 = 45.8 μmol/L, A549, IC50 = 82.8 μmol/L). Ref: A. Lin, et al, Arch. Pharm. Res., 2014, 37, 839

2.13 Eremophilane Sesquiterpenoids

HO

53

OH

170 NPR07H239A Type: Simple eremophilane sesquiterpenoids. C27H36O6 Solid, [α]D25 = −71° (c = 0.258, MeOH). Source: Marine-derived fungus Xylaria sp. Pharm: Cytotoxic (variety of cancer cells, some selectivity for a CCRF-CEM leukemia line, IC50 = 0.9 μg/ mL). Ref: M. Saleem, et al, NPR, 2007, 24, 1142 (rev) O O O

O H

O

OH

171 Peribysin A (6β,7β,8α,10β)-6,7-Epoxy-11(13)-eremophilene-8,12-diol Type: Simple eremophilane sesquiterpenoids. C15H24O3 Pale yellow oil, [α]D = −63.7° (c = 4.3, EtOH). Source: Marine-derived fungus Periconia byssoides from sea hare Aplysia kurodai. Pharm: Cell-adhesion inhibitor. Ref: T. Yamada, et al, Org. Biomol. Chem., 2004, 2, 2131│T. Yamada, et al, J. Antibiot., 2005, 58, 185 H

OH OH

O

172 Peribysin F (6β,7βOH,8α)-11(13)-Eremophilene-6,7,8,12-tetrol Type: Simple eremophilane sesquiterpenoids. C15H26O4 Pale yellow oil, [α]D22 = −21.5° (c = 0.1, EtOH). Source: Marine-derived fungus Periconia byssoides OUPS-N133. Pharm: Cell-adhesion inhibitor. Ref: T. Yamada, et al, J. Antibiot., 2005, 58, 185 H

OH 7

OH OH

OH

54

2 Sesquiterpenoids

173 Peribysin G (6β,7αOH,8α)-11(13)-Eremophilene-6,7,8,12-tetrol Type: Simple eremophilane sesquiterpenoids. C15H26O4 Needles (hexane/CH2Cl2), mp 187–189 °C, [α]D22 = −1.3° (c = 0.1, EtOH). Source: Marine-derived fungus Periconia byssoides OUPS-N133. Pharm: Cell-adhesion inhibitor. Ref: T. Yamada, et al, J. Antibiot., 2005, 58, 185 H

OH 7

OH OH

OH

174 Peribysin J Type: Simple eremophilane sesquiterpenoids. C15H26O5 Pale yellow oil, [α]D22 = −190.1° (c = 0.28, EtOH). Source: Marine-derived fungus Periconia byssoides OUPSN133 from sea hare. Pharm: Cell-adhesion inhibitor (IC50 = 11.8 μmol/L, immune system activity). Ref: T. Yamada, et al, J. Antibiot., 2007, 60, 370 HO

H

OH OH OH OH

175 Cryptosphaerolide Type: Furanoeremophilane sesquiterpenoids. C26H42O7 Colorless oil, [α]D = +22.6° (c = 0.27, CHCl3). Source: Marine-derived fungus Cryptosphaeria sp. from an unidentified ascidian (Bahamas). Pharm: Protein Mcl-1 inhibitor (Mcl-1/Bak fluorescence resonance energy transfer assay (FRET), IC50 = 11.4 μmol/L, a cancer drug target implicated in apoptosis); cytotoxic (HCT116 cells, IC50 = 4.5 μmol/L, significant). Ref: H. Oh, et al, JNP, 2010, 73, 998 O O OH

O

OH O

OH H

176 Microsphaeropsisin Type: Furanoeremophilane sesquiterpenoids. C16H22O4 Powder, mp 152–154 °C, [α]D25 = −97.7° (c = 0.13, CHCl3). Source: Marine-derived fungus Microsphaeropsis sp. from sponge Myxilla incrustans. Pharm: Antifungal (Eurotium repens, Mycotypha microspora, Ustilago violacea). Ref: U. Höller, et al, JNP, 1999, 62, 114

2.13 Eremophilane Sesquiterpenoids

OH

55

O

O OMe

177 Peribysin B (6β,7β,8α,10β,11βOH)-6,7:8,13-Diepoxy-11,12-eremophilanediol Type: Furanoeremophilane sesquiterpenoids. C15H24O4 Pale yellow oil, [α]D = +42.9° (c = 0.07, EtOH). Source: Marine-derived fungus Periconia byssoides from sea hare Aplysia kurodai. Pharm: Cell-adhesion inhibitor. Ref: T. Yamada, et al, Org. Biomol. Chem., 2004, 2, 2131 H

H O OH

O

OH

178 Peribysin C (6β,8α,10β)-8,12-Epoxy-7(11)-eremophilene-6,13-diol Type:Furanoeremophilane sesquiterpenoids. C15H24O3 Pale yellow oil, [α]D = +31.5° (c = 0.54, EtOH). Source: Marine-derived fungus Periconia byssoides from sea hare Aplysia kurodai. Pharm: Cell-adhesion inhibitor. Ref: T. Yamada, et al, Org. Biomol. Chem., 2004, 2, 2131│ H. Koshino, et al, Tet. Lett., 2006, 47, 4623 H

H O

OH

OH

179 Peribysin D (6β,8α,10β)-6,12-Epoxy-7(11)-eremophilene-8,13-diol Type: Furanoeremophilane sesquiterpenoids. C15H24O3 Pale yellow oil, [α]D = +4.6° (c = 0.1, EtOH). Source: Marinederived fungus Periconia byssoides from sea hare Aplysia kurodai. Pharm: Cell-adhesion inhibitor. Ref: T. Yamada, et al, Org. Biomol. Chem., 2004, 2, 2131│H. Koshino, et al, Tet. Lett., 2006, 47, 4623 H

OH

O

OH

56

2 Sesquiterpenoids

180 Peribysin H Type: Furanoeremophilane sesquiterpenoids. C15H24O4 Pale yellow oil, [α]D22 = −200.2° (c = 0.28, EtOH). Source: Marine-derived fungus Periconia byssoides from sea hare Aplysia kurodai (Japan waters). Pharm: Cell-adhesion inhibitor (inhibits adhesion of HL60 cells to HUVEC cells, more potently than standard control Herbimycin A). Ref: T. Yamada,et al, J. Antibiot., 2006, 59, 345 HO

H

OH

OH

O

181 Peribysin I Type:Furanoeremophilane sesquiterpenoids. C15H24O4 Pale yellow oil, [α]D22 = −34.1° (c = 0.14, EtOH). Source: Marine-derived fungus Periconia byssoides from sea hare Aplysia kurodai (Japan waters). Pharm: Cell-adhesion inhibitor (inhibits adhesion of HL60 cells to HUVEC cells, more potently than standard control Herbimycin A). Ref: T. Yamada,et al, J. Antibiot., 2006, 59, 345 H

HO

H O

OH

OH

2.14 Nardosinane Sesquiterpenoids 182 2-Deoxylemnacarnol 7,12-Epoxy-1(10)-nardosinen-7-ol Type: Nardosinane sesquiterpenoids. C15H24O2 Cryst., mp 101–103 °C, [α]D = −165° (c = 0.1, CHCl3). Source: Soft corals Paralemnalia thyrsoides (Green I., Taiwan), Lemnalia africana, Lemnalia laevis and Paralemnalia thyrsoides (Townsville area). Pharm: Neuroprotective (neuroblastoma SH-SY5Y cells, reduces 6-OHDA-induced neurotoxicity, relative neuroprotective activities at 0.01 μmol/L, 0.1 μmol/L, 1.0 μmol/L and 10 μmol/L are (10.1 ± 1.9)%, (44.8 ± 4.5)%, (30.2 ± 1.2)% and (38.9 ± 2.7)%, respectively). Ref: D. Daloze, et al, Bull. Soc. Chim. Belg., 1977, 86, 47│B. F. Bowden, et al, Aust. J. Chem., 1980, 33, 885│C. -Y. Huang, et al, Mar. Drugs, 2011, 9, 1543

H

OH O

2.14 Nardosinane Sesquiterpenoids

57

183 2-Deoxy-7-O-methyllemnacarnol 7,2-Epoxy-7methoxy-1(1)-nardosinene Type: Nardosinane sesquiterpenoids. C16H26O2 Oil. Source: Soft corals Paralemnalia thyrsoides (Green I., Taiwan) and Nephthea sp. Pharm: Neuroprotective (neuroblastoma SH-SY5Y cells, reduces 6-OHDA-induced neurotoxicity, relative neuroprotective activities at 0.0001 μmol/L, 0.001 μmol/L and 0.01 μmol/L are (13.5 ± 3.5)%, (24.5 ± 7.9)% and (16.7 ± 2.2)%, respectively). Ref: M. M. Kapojos, et al, CPB, 2008, 56, 332│C. -Y. Huang, et al, Mar. Drugs, 2011, 9, 1543

H

O O

184 Paralemnolide A Type: Nardosinane sesquiterpenoids. C15H22O5 Colorless viscous oil; [α]D25 = −25° (c = 0.4, CHCl3). Source: Soft coral Paralemnalia thyrsoides (Taitung County, Taiwan). Pharm: Cytotoxic (P388, ED50 = 3.8 μg/mL, A549 and HT29, inactive, ED50 > 50 μg/mL). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 1528 OH O

O O O

185 Paralemnolin M Type: Nardosinane sesquiterpenoids. C19H28O4 Source: Soft coral Paralemnalia thyrsoides (Green I., Taiwan). Pharm: Cytotoxic (mild). Ref: G. -H. Wang, et al, CPB, 2010, 58, 30 O H

O

O O

186 Paralemnolin N Type: Nardosinane sesquiterpenoids. C19H28O4 Source: Soft coral Paralemnalia thyrsoides (Green I., Taiwan). Pharm: Cytotoxic (mild). Ref: G. -H. Wang, et al, CPB, 2010, 58, 30

58

2 Sesquiterpenoids

O H

O

O O

187 Paralemnolin Q Type: Nardosinane sesquiterpenoids. C15H22O3 White solid; mp 118 °C, [α]D26 = +26° (c = 0.24, CHCl3). Source: Soft coral Paralemnalia thyrsoides (Green I., Taiwan). Pharm: Neuroprotective (neuroblastoma SH-SY5Y cells, reduces 6-OHDA neurotoxicity, relative neuroprotective activities at 0.01 μmol/L, 0.1 μmol/L, 1.0 μmol/L and 10 μmol/L are (8.7 ± 2.5)%, (20.2 ± 14.0)%, (16.2 ± 3.5)% and (11.2 ± 1.3)%, respectively). Ref: C. -Y. Huang, et al, Mar. Drugs, 2011, 9, 1543 OH O O H

188 Paralemnolin S Type: Nardosinane sesquiterpenoids. C15H22O3 Colorless oil, [α]D24 = +83° (c = 0.08, CHCl3). Source: Soft coral Paralemnalia thyrsoides (Green I., Taiwan). Pharm: Neuroprotective (neuroblastoma SH-SY5Y cells, reduces 6-OHDA neurotoxicity, relative neuroprotective activities at 0.0001 μmol/L, 0.001 μmol/L, 0.01 μmol/L and 0.10 μmol/L are (6.1 ± 2.6)%, (16.2 ± 5.1)%, (25.2 ± 3.4)% and (10.2 ± 5.3)%, respectively). Ref: C. -Y. Huang, et al, Mar. Drugs, 2011, 9, 1543 O O O H

2.15 Cadinane Sesquiterpenoids 189 6-Hydroxy-α-muurolene 4,9-Muuroladien-6-ol Type: Cadinane sesquiterpenoids. C15H24O Yellow oil, [α]D = +23° (c = 1.41, CHCl3). Source: Soft coral Heteroxenia sp. (Philippines). Pharm: Antifungal. Ref: R. A. Edrada, et al, Z. Naturforsch., C: Biosci, 2000, 55, 82

2.15 Cadinane Sesquiterpenoids

59

H

OH

190 (–)-8-Hydroxysclerosporin 8-Hydroxy-4,9-cadinadien-14-oic acid Type: Cadinane sesquiterpenoids. C15H22O3 Amorph. solid, [α]D23 = −62° (c = 0.033, CHCl3). Source: Marine-derived fungus Cadophora malorum from green alga Enteromorpha sp. Pharm: Fat-accumulation inhibitor (3T3-L1 murine adipocytes, inhibition of triglyceride accumulation, IC50 = 212 μmol/L, along with cytotoxic, IC50 = 304 μmol/L). Ref: C. Almeida, et al, JNP, 2010, 73, 476 O

OH

H 8

OH

H

191 (+)-10-Isothiocyanato-4-amorphene Type: Cadinane sesquiterpenoids. C16H25NS Oil, [α]D = +100.45° (c = 5.47, CCl4). Source: Sponge Axinyssa fenestratus (Fiji), nudibranch Phyllidia pustulosa. Pharm: Anthelmintic; antibarnacle (larval antisettlement agent and development inhibitor). Ref: K. A. Alvi, et al, JNP, 1991, 54, 71│T. Okino, et al, Tetrahedron, 1996, 52, 9447 H

NCS

H

192 Scabralin A Type: Cadinane sesquiterpenoids. C15H24O2 Source: Soft coral Sinularia scabra (Southern Taiwan). Pharm: Cytotoxic (MCF7, ED50 = 9.6 μg/mL; WiDr, ED50 = 10.7 μg/ mL; Doay, ED50 = 7.6 μg/mL; Hep2, ED50 = 13.8 μg/mL); anti-inflammatory (LPS-stimulated RAW264.7 macrophage cells, inhibits LPS-induced upregulation of pro-inflammatory iNOS and COX-2 proteins, 10 μmol/L, reduces level of iNOS protein to (39.1 ± 15.9)% relative to control cells stimulated with LPS only, no effects to accumulation of COX-2 protein). Ref: J. -H. Su, et al, Arch. Pharmacal Res., 2012, 35, 779

60

2 Sesquiterpenoids

HO

O

H

193 (+)-Sclerosporin 4,9-Cadinadien-14-oic acid Type: Cadinane sesquiterpenoids. C15H22O2 Cryst. (petrol), mp 159–160 °C, [α]D20 = +11.1° (c = 0.035, MeOH), rare example of a fungal–derived cadinane–type sesquiterpene. Source: Marine-derived fungus Cadophora malorum from green alga Enteromorpha sp., terrestrial fungus (Sclerotinia fruticula). Pharm: Antifungal (sporogenic). Ref: M. Katayama, et al, Tet. Lett., 1979, 20, 1773; 1983, 24, 1703; 1984, 25, 4685│K. Sawai, et al, Agric. Biol. Chem., 1985, 49, 2501│C. Almeida,et al, JNP, 2010, 73, 476 O

OH

H

H

194 T-cadinthiol Type: Cadinane sesquiterpenoids. C15H26S Oil, [α]D = −24.3° (c = 1.06, CHCl3). Source: Sponge Cymbastela hooperi (Kelso Reef, Great Barrier Reef). Pharm: Antiplasmodial (Plasmodium falciparum clone D6, IC50 = 3.6 μg/mL). Ref: G. M. König, et al, JOC, 1997, 62, 3837 H

SH

H

195 Thespone Type: Cadinane sesquiterpenoids. C15H12O3 Red needles (CHCl3/C6H6), mp 196–197 °C. Source: Mangrove Thespesia populnea. Pharm: Cytotoxic; superoxide anion generator. Ref: S. Neelakantan, et al, Indian J. Chem., Sect. B, 1983, 22, 95│J. J. Inbaraj, et al, Free Radical Biol. Med., 1999, 26, 1072; CA, 131, 153529c

2.16 Drimane Sesquiterpenoids

61

O O O

2.16 Drimane Sesquiterpenoids 196 11-Acetoxy-8-drimen-12,11-olide Type: Drimane sesquiterpenoids. C17H24O4 Oil, Colorless oil, [α]D25 = −7.2° (c = 0.1, MeOH). Source: Sponge Dysidea sp. (Guam). Pharm: Na/K-ATPase inhibitor (IC50 = 98 μmol/L). Ref: V. J. Paul, et al, JNP, 1997, 60, 1115 O O O O

H

197 6β-Acetoxyolepupuane Type: Drimane sesquiterpenoids. C21H30O7 [α]D = −118.7° (c = 1.3, CHCl3). Source: Nudibranch Dendrodoris grandiflora. Pharm: Feeding deterrent (Carassius auratus). Ref: G. Cimino, et al, Tetrahedron, 1985, 41, 1093 O O O

O O

O

O

198 Albican-11,14-diol Type: Drimane sesquiterpenoids. C15H26O2 Source: Marine-derived fungus Aspergillus versicolor from green alga Codium fragile (Dalian, China). Pharm: Toxic (brine shrimp, potent); antibacterial (Escherichia coli and Staphylococcus aureus). Ref: X. -H. Liu, et al, Nat. Prod. Commun., 2012, 7, 819

62

2 Sesquiterpenoids

OH

H

HO

199 (+)-Albicanol Type: Drimane sesquiterpenoids. C15H26O mp 68–69 °C, [α]D = +13° (c = 0.6, CHCl3); mp 70 °C, [α]D = +12.8° (c = 1.14, CHCl3). Source: Dorid nudibranches Cadlina luteomarginata (Vancouver, Canada) and Cadlina luteomarginata. Pharm: Ichthyotoxic; antitumour promoting activity. Ref: J. Hellou, et al, Tetrahedron, 1982, 38, 1875│A. K. Bannerjee, et al, J. Chem. Res. (S), 1998, 710│A. T. Anilkumar, et al, Tetrahedron, 2000, 56, 1899│H. Akita, et al, Tetrahedron: Asymmetry, 2000, 11, 1375│H. Ito, et al, CPB, 2000, 48, 1190 OH

H

200 (+)-Albicanol acetate (5α,9β,10β)-8(12)-Drimen-11-ol acetate Type: Drimane sesquiterpenoids. C17H28O2 Oil, [α]D = +24° (c = 0.5, CHCl3); [α]D = +33.9° (c = 1.34, CHCl3), [α]D23 = +26.2° (c = 1.3, CHCl3). Source: Dorid nudibranch Cadlina luteomarginata (Vancouver, Canada). Pharm: Antifeedant (5 μg/mL); ichthyotoxic; antitumour promoting activity. Ref: J. Hellou, et al, Tetrahedron, 1982, 38, 1875│J. Kubanek, et al, JOC, 1997, 62, 7239│H. Ito, et al, CPB, 2000, 48, 1190│A. T. Anilkumar, et al, Tetrahedron, 2000, 56, 1899│H. Akita, et al, Tetrahedron: Asymmetry, 2000, 11, 1375 O O

H

201 Antibiotic RES-1149-2 Type: Drimane sesquiterpenoids. C23H30O5 Powder, mp 131–134 °C, [α]D = −358° (c = 0.1, MeOH). Source: Marine-derived fungus Aspergillus ustus from sponge Suberites domuncula (Mediterranean Sea), mangrove-derived fungus Aspergillus ustus from mangrove Bruguiera gymnorrhiza (rhizosphere soil, China). Pharm:

2.16 Drimane Sesquiterpenoids

63

Cytotoxic (panel of tumour cell lines); endothelin receptor binding agent. Ref: P. Proksch, et al, Bot. Mar., 2008, 51, 209│H. B. Liu, et al, JNP, 2009, 72, 1585│Z. Y. Lu, et al, JNP, 2009, 72, 1761 O HO

O 11

6

H

O O

202 7-Deacetoxyolepupuane Type: Drimane sesquiterpenoids. C17H26O3 Cryst. (CH2Cl2/hexane), mp 83–85 °C, [α]D = −166.7° (c = 0.104, CHCl3). Source: Sponge Dysidea sp. (Guam), nudibranches Dendrodoris limbata and Dendrodoris grandiflora. Pharm: Antibacterial (inhibits bioluminescence reaction, symbiotic luminous bacterium Photobacterium leiognathi of tropical fish, IC50 = 90–145 μmol/L); antifeedant; ichthyotoxin. Ref: C. Avila, et al, Experientia, 1991, 47, 306│M. J. Garson, et al, JNP, 1992, 55, 364│V. J. Paul, et al, JNP, 1997, 60, 1115 O O O

H H

203 Dendrocarbin J 11β-Ethoxy-7α-hydroxy-8-drimen-12,11-olide Type: Drimane sesquiterpenoids. C17H26O4 Oil, [α]D25 = +17° (c = 0.06, CHCl3). Source: Nudibranch Dendrodoris carbunculosa. Pharm: Cytotoxic (MDR tumour cell lines). Ref: Y. Sakio, et al, JNP, 2001, 64, 726 O

O O

H

OH

204 (E,E)-6-(6′,7′-dihydroxy-2′,4′-octadienoyl)-strobilactone A Type: Drimane sesquiterpenoids. C23H32O7 Glassy material, [α]D21 = −155° (c = 0.21, CHCl3); amorph. powder, [α]D20 = −156° (c = 0.1, MeOH). Source: Marine-derived fungi Aspergillus insuetus OY-207 from sponge Psammocinia sp. (Sdot-Yam, Israel) and

64

2 Sesquiterpenoids

Aspergillus ustus from sponge Suberites domuncula (Mediterranean Sea). Pharm: Antifungal (Neurospora crassa, MIC = 162 μmol/L). Ref: P. Proksch, et al, Bot. Mar., 2008, 51, 209│H. Liu, et al, JNP, 2009, 72, 1585│E. Cohen, et al, BoMC, 2011, 19, 6587 O

O

OH

H

OH O O

OH

205 11,12-Drimanolide Type: Drimane sesquiterpenoids. C15H24O2 White solid, mp 75–76 °C, [α]D25 = +14.4° (c = 0.3, MeOH). Source: Sponge Dysidea sp. (Guam). Pharm: Antibacterial (inhibits bioluminescence reaction, symbiotic luminous bacterium Photobacterium leiognathi of tropical fish, IC50 = 90–145 μmol/L); Na/K-ATPase inhibitor (IC50 = 45 μmol/L); PLA2 inhibitor (IC50 = 113 μmol/L). Ref: V. J. Paul, et al, JNP, 1997, 60, 1115 O

O

H

206 7-Drimen-11-carboxylic acid 2,3-dihydroxypropyl ester Type: Drimane sesquiterpenoids. C18H30O4 [α]D = +23.1° (c = 0.9, CHCl3). Source: Nudibranch Archidoris montereyensis. Pharm: Antifeedant (fish, EC = 18 μg/mg). Ref: K. Gustafson, et al, Tet. Lett., 1984, 25, 11│K. Gustafson, et al, Tetrahedron, 1985, 41, 1101│N. Ungar, et al, Tetrahedron: Asymmetry, 1999, 10, 1263 OH O

O OH

207 (6β,9α)-11,12-Epoxy-11-ketone-7-drimene-6-O-(5-carboxy-2E, 4E-pentadienoyl)-6,9-diol Type: Drimane sesquiterpenoids. C21H26O7 Amorph. powder, [α]D20 = −157° (c = 0.1, MeOH). Source: Marine-derived fungus Aspergillus ustus from sponge Suberites domuncula (Mediterranean Sea). Pharm: Cytotoxic (panel of tumour cell lines). Ref: P. Proksch, et al, Bot. Mar., 2008, 51, 209│H. B. Liu,et al, JNP, 2009, 72, 1585

2.16 Drimane Sesquiterpenoids

O

65

O

OH

H

O O

OH O

208 Epoxyphomalin A Type: Drimane sesquiterpenoids. C22H32O5 Source: Marine-derived fungi Paraconiothyrium cf. sporulosum from sponge Ectyoplasia ferox (Lauro Club Reef, Dominica, Caribbean) and Phoma sp. from sponge Ectyoplasia ferox (Caribbean Sea, Dominica). Pharm: Cytotoxic (panel of 36 hmn tumour cells, extremely potent, displayed significant selectivity toward 12 of cell lines and possessed a unique cytotoxic selectivity pattern as determined by COMPARE analyses, BXF-1218L, IC50 = 0.017 μg/ mL; BXF-T24, IC50 = 0.374 μg/mL; CNXF-498NL, IC50 = 0.022 μg/mL; CNXF-SF268, IC50 = 0.354 μg/mL; CXF-HCT116, IC50 = 0.329 μg/mL; CXF-HT29, IC50 = 0.198 μg/mL; GXF-251L, IC50 = 0.034 μg/mL; HNXF-536L, IC50 = 0.247 μg/mL; LXF-1121L, IC50 = 0.381 μg/mL; LXF-289L, IC50 = 0.426 μg/mL; LXF-526L, IC50 = 0.430 μg/mL; LXF-529L, IC50 = 0.079 μg/mL; LXF-629L, IC50 = 0.038 μg/mL; LXF-H460, IC50 = 0.307 μg/mL; MAXF-401NL, IC50 = 0.010 μg/mL; MAXF-MCF7, IC50 = 0.116 μg/ mL; MEXF-276L, IC50 = 0.047 μg/mL; MEXF-394NL, IC50 = 0.278 μg/mL; MEXF-462NL, IC50 = 0.058 μg/mL; MEXF-514L, IC50 = 0.383 μg/mL; MEXF-520L, IC50 = 0.316 μg/mL; OVXF-1619L, IC50 = 0.258 μg/mL; OVXF-899L, IC50 = 0.080 μg/mL; OVXF-OVCAR3, IC50 = 0.017 μg/mL; PAXF-1657L, IC50 = 0.027 μg/mL; PAXF-PANC1, IC50 = 0.330 μg/ mL; PRXF-22RV1, IC50 = 0.034 μg/mL; PRXF-DU145, IC50 = 0.745 μg/mL; PRXF-LNCAP, IC50 = 0.937 μg/mL; PRXF-PC3M, IC50 = 0.017 μg/mL; PXF-1752L, IC50 = 0.033 μg/mL; RXF-1781L, IC50 = 0.469 μg/mL; RXF-393NL, IC50 = 0.080 μg/mL; RXF-486L, IC50 = 0.034 μg/mL; RXF-944L, IC50 = 0.316 μg/mL; UXF-1138L, IC50 = 0.031 μg/mL; mean, IC50 = 0.114 μg/mL) (Mohamed, 2009); cytotoxic (mode of action is inhibition of proteasomes, inhibits chymotrypsin-like, caspase-like, and trypsin-like activity of purified 20S-proteasomes) (Mohamed, 2010). Ref: I. E. Mohamed, et al, Org. Lett., 2009, 11, 5014│I. E. Mohamed, et al, JNP, 2010, 73, 2053 HO O

OH O

H

OH

66

2 Sesquiterpenoids

209 Epoxyphomalin B Type: Drimane sesquiterpenoids. C22H32O4 Source: Marine-derived fungi Paraconiothyrium cf. sporulosum from sponge Ectyoplasia ferox (Lauro Club Reef, Dominica, Caribbean) and Phoma sp. from sponge Ectyoplasia ferox (Caribbean Sea, Dominica). Pharm: Cytotoxic (panel of 36 hmn tumour cells, BXF-1218L, IC50 = 0.606 μg/mL; BXF-T24, IC50 = 0.402 μg/mL; CNXF-498NL, IC50 = 0.904 μg/mL; CNXF-SF268, IC50 = 0.338 μg/mL; CXF-HCT116, IC50 = 2.245 μg/mL; CXF-HT29, IC50 = 0.593 μg/mL; GXF-251L, IC50 = 11.42 μg/mL; HNXF-536L, IC50 = 0.326 μg/mL; LXF-1121L, IC50 = 1.584 μg/mL; LXF-289L, IC50 = 3.604 μg/mL; LXF-526L, IC50 = 10.00 μg/mL; LXF-529L, IC50 = 9.501 μg/mL; LXF-629L, IC50 = 1.920 μg/mL; LXFH460, IC50 = 10.51 μg/mL; MAXF-401NL, IC50 = 0.501 μg/mL; MAXF-MCF7, IC50 = 0.398 μg/mL; MEXF-276L, IC50 = 3.764 μg/mL; MEXF-394NL, IC50 = 0.338 μg/ mL; MEXF-462NL, IC50 = 2.443 μg/mL; MEXF-514L, IC50 = 1.425 μg/mL; MEXF-520L, IC50 = 1.920 μg/mL; OVXF-1619L, IC50 = 0.278 μg/mL; OVXF-899L, IC50 = 2.623 μg/mL; OVXF-OVCAR3, IC50 = 0.910 μg/mL; PAXF-1657L, IC50= 1.481 μg/mL; PAXF-PANC1, IC50 = 0.523 μg/mL; PRXF-22RV1, IC50 = 0.589 μg/mL; PRXF-DU145, IC50 = 1.813 μg/ mL; PRXF-LNCAP, IC50 = 0.774 μg/mL; PRXF-PC3M, IC50 = 0.546 μg/mL; PXF-1752L, IC50 = 0.251 μg/mL; RXF-1781L, IC50 = 2.656 μg/mL; RXF-393NL, IC50 = 1.098 μg/mL; RXF-486L, IC50 = 3.657 μg/mL; RXF-944L, IC50 = 0.380 μg/mL; UXF-1138L, IC50 = 1.811 μg/mL; mean, IC50 = 1.249 μg/mL) (Mohamed, 2009); cytotoxic (mode of action is inhibition of proteasomes, inhibits chymotrypsin-like, caspase-like, and trypsin-like activity of purified 20S-proteasomes) (Mohamed, 2010). Ref: I. E. Mohamed, et al, Org. Lett., 2009, 11, 5014│I. E. Mohamed, et al, JNP, 2010, 73, 2053

O

OH O

H

OH

210 Hodgsonal 2α,11β-Diacetoxy-7-drimen-12-al Type: Drimane sesquiterpenoids. C19H28O5 Oil, [α]D = −6.45° (c = 1.2, CHCl3). Source: Nudibranch Bathydoris hodgsoni (Antarctic). Pharm: Predator deterrent. Ref: K. Iken, et al, Tet. Lett., 1998, 39, 5635 O O

O

O

O H

H

2.16 Drimane Sesquiterpenoids

67

211 Insulicolide A Type: Drimane sesquiterpenoids. C22H25NO8 Cryst. or pale yellow solid, mp 184– 185 °C, mp 193 °C (dec), [α]D22 = −360° (c = 0.0025, EtOH), [α]D = −204° (c = 0.41, MeOH). Source: Marine-derived fungus Aspergillus versicolor from green alga Penicillus capitatus (surface, Caribbean), marine-derived fungus Aspergillus insulicola from various algae (Bahamas). Pharm: Cytotoxic (NCI’s 60 cell-line panel, mean LC50 = 1.1 μg/mL); cytotoxic (HCT116 cells, LC50 = 0.44 μg/mL, panel of renal carcinoma cell lines). Ref: L. Rahbæk, et al, JNP, 1997, 60, 811│G. N. Belofsky, et al, Tetrahedron, 1998, 54, 1715 O O OH HO

NO2

O O

212 11-O-Methyl-11,12-epoxy-11-drimanol Type: Drimane sesquiterpenoids. C16H28O2 Colorless oil, [α]D25 = −21.6° (c = 0.3, MeOH). Source: Sponge Dysidea sp. (Guam). Pharm: Antibacterial (inhibits bioluminescence reaction, symbiotic luminous bacterium Photobacterium leiognathi of tropical fish, IC50 = 90–145 μmol/L). Ref: V. J. Paul, et al, JNP, 1997, 60, 1115 O

O

H

213 Polygodial Type: Drimane sesquiterpenoids. C15H22O2 Needles (petrol), mp 57 °C, mp 50 °C, bp0.8mmHg 138–140 °C, [α]D = −210° (90% EtOH). Source: Sponge Dysidea sp. (Guam), nudibranches Dendrodoris krebsii, Dendrodoris limbata, Dendrodoris nigra and Dendrodoris tuberculosa, terrestrial plants (Polygonum hydropiper and Drimys lanceolata). Pharm: Antibacterial (inhibits bioluminescence reaction, symbiotic luminous bacterium Photobacterium leiognathi of tropical fish, 10 μg/ mL, IZD = 8 mm, IC50 = 11.4 μmol/L); Na/K-ATPase inhibitor (IC50 = 82 μmol/L); antinociceptive; plant growth regulator; insect growth regulator; helicocide; antifeedant (insect). Ref: G. Cimino, et al, Experientia, 1985, 41, 1335│V. J. Paul, et al, JNP, 1997, 60, 1115

68

2 Sesquiterpenoids

H

O

H O

H

214 Purpurogemutantidin Type: Drimane sesquiterpenoids. C22H32O4 Colorless oil (MeOH), [α]D20 = −13.7° (c = 0.1, CHCl3), [α]D20 = −9.3° (c = 0.5, MeOH). Source: Marine-derived fungus Penicillium purpurogenum (sediment, Bohai Bay, Tianjin, China). Pharm: Cytotoxic (K562, IC50 = 0.93 μmol/L; HL60, IC50 = 2.48 μmol/L; HeLa, IC50 = 16.6 μmol/L; BGC823, IC50 = 31.0 μmol/L; MCF7, IC50 = 26.3 μmol/L). Ref: S. -M. Fang, et al, Mar. Drugs, 2012, 10, 1266 OH O

O OH

H

215 Purpurogemutantin Type: Drimane sesquiterpenoids. C24H34O6 White crystalline powder (MeOH), mp 122–123 °C, [α]D20 = +21.0° (c = 1.0, MeOH). Source: Marine-derived fungus Penicillium purpurogenum (sediment, Bohai Bay, Tianjin, China). Pharm: Cytotoxic (K562, IC50 = 13.4 μmol/L; HL60, IC50 = 18.1 μmol/L; HeLa, IC50 = 18.9 μmol/L; BGC823, IC50 = 33.0 μmol/L; MCF7, IC50 = 29.3 μmol/L). Ref: S. -M. Fang, et al, Mar. Drugs, 2012, 10, 1266 OH OH O O

OH

O

H

216 Strobilactone A Type: Drimane sesquiterpenoids. C15H22O4 Glassy material, [α]D21 = −164° (c = 0.35, CHCl3). Source: Marine-derived fungus Aspergillus insuetus OY-207 from sponge

2.16 Drimane Sesquiterpenoids

69

Psammocinia sp. (Sdot-Yam, Israel), terrestrial fungus (Strobilurus ohshimae, edible mushroom). Pharm: Antifungal (Neurospora crassa, MIC = 242 μmol/L). Ref: Y. Shiono, et al, Z. Naturforsch., B, 2007, 62, 1585│E. Cohen, et al, BoMC, 2011, 19, 6587 O HO

H

O

OH

217 Ustusolate A Type: Drimane sesquiterpenoids. C23H34O5 Oil, [α]D20 = −68° (c = 0.1, MeOH). Source: Mangrove-derived fungus Aspergillus ustus from mangrove Bruguiera gymnorrhiza (rhizosphere soil, China). Pharm: Cytotoxic (A549 cells, IC50 = 30.0 μmol/L, control VP-16, IC50 = 0.63 μmol/L, HL60 cells, IC50 = 20.6 μmol/L, VP-16, IC50 = 0.042 μmol/L). Ref: Z. Lu, et al, JNP, 2009, 72, 1761 OH OH OH

9

10 5

6

H

O O

218 Ustusolate C Type: Drimane sesquiterpenoids. C23H32O6 Oil, [α]D20 = −700° (c = 0.1, MeOH). Source: Mangrove-derived fungus Aspergillus ustus from mangrove Bruguiera gymnorrhiza (rhizosphere soil, Wenchang, Hainan Province, China). Pharm: Cytotoxic (A549, IC50 = 10.5 μmol/L, control VP-16, IC50 = 0.63 μmol/L, HL60, IC50 > 100 μmol/L). Ref: Z. Lu, et al, JNP, 2009, 72, 1761 O O

HO

11 9 6

H

O

OH O

70

2 Sesquiterpenoids

219 Ustusolate E Type: Drimane sesquiterpenoids. C21H26O6 Amorph. powder or oil, [α]D20 = −320° (c = 0.1, MeOH), [α]D20 = −164° (c = 0.1, MeOH). Source: Marine-derived fungi Aspergillus ustus from sponge Suberites domuncula (Adriatic Sea) and Aspergillus ustus from sponge Suberites domuncula (Mediterranean Sea), mangrove-derived fungus Aspergillus ustus from mangrove Bruguiera gymnorrhiza (rhizosphere soil, Wenchang, Hainan Province, China). Pharm: Cytotoxic (L5178Y, EC50 = 0.6 μg/mL); cytotoxic (A549, IC50 > 100 μmol/L, HL60, IC50 = 9.0 μmol/L, control VP-16, IC50 = 0.042 μmol/L). Ref: P. Proksch, et al, Bot. Mar., 2008, 51, 209│H. B. Liu,et al, JNP, 2009, 72, 1585│Z. Lu, et al, JNP, 2009, 72, 1761 O O

OH O H

O

H O

220 14(4→5),15(10→9)-Bisabeo-3-drimene-11-carboxylic acid Type: Nor- and seco-drimane sesquiterpenoids. C16H26O2 Oil. Source: Sponge Dysidea sp. (New Zealand). Pharm: Antibacterial (Bacillus subtilis, IC50 = 5 μg/mL); antifungal (Trichophyton mentagrophytes, IC50 = 8 μg/mL). Ref: M. Stewart, et al, Aust. J. Chem., 1997, 50, 341 O

H

OH

221 Diacetyl-12-nor-8,11-drimanediol Type: Nor- and seco-drimane sesquiterpenoids. C18H30O4 White solid, mp 84−85 °C, [α]D25 = +36° (c = 0.2, MeOH). Source: Sponge Dysidea sp. (Guam). Pharm: Antibacterial (inhibits bioluminescence reaction, symbiotic luminous bacterium Photobacterium leiognathi of tropical fish, IC50 = 90–145 μmol/L). Ref: V. J. Paul, et al, JNP, 1997, 60, 1115

2.17 Guaiane Sesquiterpenoids

71

O O O

O

H

2.17 Guaiane Sesquiterpenoids 222 Anthogorgiene G Type: Simple guaiane sesquiterpenoids. C30H34O3 Source: Gorgonian Anthogorgia sp. (Weizhou I., Giuangxi, China). Pharm: Antifoulant (in vitro, Balanus amphitrite); antimicrobial. Ref: D. Chen, et al, J. Agric. Food Chem., 2012, 60, 112

HO O O

223 8,9-Dihydro-linderazulene 9,10-Dihydro-linderazulene Type: Simple guaiane sesquiterpenoids. C15H16O [α]D25 = −38.2° (c = 0.07, hexane). Source: Gorgonian Echinogorgia complexa. Pharm: Inhibits mitochondrial respiratory chain (IC50 = 2.5–4.3 μmol/L). Ref: E. Manzo, et al, Tet. Lett., 2007, 48, 2569

O

224 (1S*,4R*,7S*,10R*)-1,7-Epidioxy-5-guaiene Type: Simple guaiane sesquiterpenoids. C15H24O2 [α]D = −49.4° (c = 0.27, CHCl3). Source: Sponge Axinyssa sp. Pharm: Antifoulant (cypris larvae of barnacle Balanus amphitrite). Ref: H. Hirota, et al, Tetrahedron, 1998, 54, 13971

72

2 Sesquiterpenoids

O

O

225 Guaiazulene 7-Isopropyl-1,4-dimethylazulene Type: Simple guaiane sesquiterpenoids. C15H18 Blue–violet plates (EtOH) or blue oil, mp 31.5 °C, bp12mmHg 167–168 °C. Source: Soft coral Alcyonium sp., gorgonian Euplexaura erecta. Pharm: Antimicrobial; toxicity (LD50 (rat, orl) = 1550 mg/kg). Ref: N. Fusetani, et al, Experientia, 1981, 37, 680│B. F. Bowden, et al, Aust. J. Chem., 1983, 36, 211

2

12

226 Hydroxycolorenone Type: Simple guaiane sesquiterpenoids. C15H24O2 [α]D = +58.6° (c = 0.46, CHCl3). Source: Soft coral Nephthea chabrolii (Indonesia). Pharm: Insecticide (larvae of pest insect Spodoptera littoralis). Ref: D. Handayani, et al, JNP, 1997, 60, 716 H O

OH

227 Isoechinofuran Type: Simple guaiane sesquiterpenoids. C15H18O [α]D25 = −2.8° (c = 0.07, hexane). Source: Gorgonian Echinogorgia complexa. Pharm: Inhibits mitochondrial respiratory chain (IC50 = 2.5–4.3 μmol/L). Ref: E. Manzo, et al, Tet. Lett., 2007, 48, 2569

O

2.17 Guaiane Sesquiterpenoids

73

228 Linderazulene 3,5,8-Trimethylazuleno[6,5-b]furan Type: Simple guaiane sesquiterpenoids. C15H15O Lustrous violet–black plates (2–propanol), mp 106–107 °C. Source: Gorgonian Paramuricea chamaeleon. Pharm: Immunodepressant. Ref: S. Imre, et al, Experientia, 1981, 37, 442

O

229 Menelloide E Type: Simple guaiane sesquiterpenoids. C15H18O4 Colorless oil; [α]D25 = +9° (c = 0.05, CHCl3). Source: Gorgonian Menella sp. (southern coast of Taiwan). Pharm: Antioxidant (superoxide anion •O2- scavenger, 10 μg/mL, InRt = (19.85 ± 6.65)%, IC50 > 10 μg/mL, control DPI, IC50 = (0.80 ± 0.31)μg/mL); elastase release inhibitor (stimulated hmn neutrophils, response to fMLP/CB, 10 μg/mL, InRt = (26.99 ± 4.99)%, IC50 > 10 μg/mL, control Elastatinal, IC50 = (31.82 ± 5.92)μg/mL). Ref: C. -H. Lee, et al, Mar. Drugs, 2012, 10, 427│P. -J. Sung, et al, Biochem. Syst. Ecol., 2012, 40, 53 OH OH O

H

O H

230 Methoxycolorenone (1α,7β,10β)-11-Methoxy-4-guaien-3-one Type: Simple guaiane sesquiterpenoids. C16H26O2 Oil, [α]D = +57.4° (c = 0.31, CHCl3). Source: Soft coral Nephthea chabrolii (Indonesia). Pharm: Insecticide (larvae of pest insect Spodoptera littoralis). Ref: D. Handayani, et al, JNP, 1997, 60, 716 H O

O

231 10-Methoxy-6-guaien-4-ol O-Methylguaianediol Type: Simple guaiane sesquiterpenoids. C16H28O2 Oil, [α]D = +22° (c = 0.5, CH2Cl2). Source: Sponge Diacarnus erythraenus (Red Sea).

74

2 Sesquiterpenoids

Pharm: Cytotoxic (P388, A549 and HT29, all IC50 > 1 μg/mL). Ref: D. T. A. Youssef, et al, JNP, 2001, 64, 1332 O

H

HO H

232 Americanolide D (1α,8α,10α)-4,7(11)-Guaiadien-12,8-olide Type: 12,8-Guaianolide sesquiterpenoids. C15H20O2 Unstable yellow oil, [α]D23 = −15° (c = 1, CHCl3). Source: Gorgonian Pseudopterogorgia americana (Puerto Rico). Pharm: Cytotoxic (HeLa, ED50 = 30 μg/ mL, CHO-K1, ED50 = 100 μg/mL, KM12, IC50 = 0.1 μg/mL). Ref: A. D. Rodríguez, et al, JNP, 1997, 60, 207 H O O

233 Gorgiabisazulene Type: Dimeric guaiane sesquiterpenoids. C31H32O2 Purple amorphous solid, [α]D20 = −92° (c = 0.05, CHCl3). Source: Gorgonian Acalycigorgia sp. (Japan waters). Pharm: Cell division inhibitor (fertilized sea urchin eggs); toxic (brine shrimp). Ref: M. Ochi, et al, Chem. Lett., 1993, 2003

O

O

234 Clavukerin A Type: Seco-, cyclo-, abeo- and nor-guaiane sesquiterpenoids. C12H18 Oil, [α]D20 = −53° (CHCl3). Source: Soft coral Cespitularia sp., stolonifer Clavularia koellikeri. Pharm: Ichthyotoxin. Ref: B. F. Bowden, et al, Aust. J. Chem., 1983, 36, 211│M. Kobayashi, et al, CPB, 1983, 31, 2160; 1984, 32, 1667│M. Asaoka, et al, Chem. Lett., 1991, 1295 H 1

10

2.18 Aromadendrane Sesquiterpenoids

75

235 Clavularin A Type: Seco-, cyclo-, abeo- and nor-guaiane sesquiterpenoids. C12H18O2 Oil. Source: Stolonifer Clavularia koellikeri. Pharm: Cytotoxic. Ref: M. Endo, et al, Chem. Comm., 1983, 322; 980│K. Hiroya, et al, Synlett, 1999, 529 O

O 7

236 Clavularin B Type: Seco-, cyclo-, abeo- and nor-guaiane sesquiterpenoids. C12H18O2 Oil. Source: Stolonifer Clavularia koellikeri. Pharm: Cytotoxic. Ref: M. Endo, et al, Chem. Comm., 1983, 322; 980│K. Hiroya, et al, Synlett, 1999, 529 O

O 7

237 Hymenin Epiparthenin Type: Pseudoguaiane sesquiterpenoids. C15H18O4 Leaflets (EtOAc), mp 173–174 °C, [α]D25 = −88.7° (c = 2.1, CHCl3). Source: Sponge Axinella sp. (deep water, Great Australian Bight). Pharm: Cytotoxic. Ref: H. Zhang, et al, Tet. Lett., 2012, 53, 3784│F. Balza, et al, Phytochemistry, 1988, 27, 1421 OH 1

10

4

H O

O O

2.18 Aromadendrane Sesquiterpenoids 238 (+)-Alloaromadendrene Type: Aromadendrane sesquiterpenoids. C15H24 Colorless oil, [α]D25 = +25.8° (c = 1.6, CHCl3). Source: Soft coral Sarcophyton acutangulum (Japan waters), stolonifer Clavularia viridis (Japan waters). Pharm: Toxic (brine shrimp assay, LD50 = 3.0 μg/mL). Ref: M. Yasumoto, et al, JNP, 2000, 63, 1534

76

2 Sesquiterpenoids

H

H

239 Lochmolin A Type: Aromadendrane sesquiterpenoids. C15H22O2 Colorless oil, [α]D26 = −89° (c = 0.5, CHCl3). Source: Soft coral Sinularia lochmodes (northern coast of Taiwan). Pharm: Anti-inflammatory (LPS-stimulated RAW264.7 macrophages, inhibits accumulation of COX-2 protein, 1 μmol/L, reduces level of COX-2 to (36.6 ± 3.8)%, 10 μmol/L, to (8.7 ± 4.5)%, 100 μmol/L, to (1.7 ± 1.3)%). Ref: Y. -J. Tseng, et al, Mar. Drugs, 2012, 10, 1572 O O H

240 Lochmolin B Type: Aromadendrane sesquiterpenoids. C17H30O2 Colorless oil, [α]D26 = −173° (c = 0.8, CHCl3). Source: Soft coral Sinularia lochmodes (northern coast of Taiwan). Pharm: Anti-inflammatory (LPS-stimulated RAW264.7 macrophages, inhibits accumulation of COX-2 protein, 100 μmol/L, reduces level of COX-2 to (17.6 ± 2.2)%). Ref: Y. -J. Tseng, et al, Mar. Drugs, 2012, 10, 1572 H

OH

O H

241 Lochmolin C Type: Aromadendrane sesquiterpenoids. C15H24O3 Colorless oil, [α]D26 = −261° (c = 0.6, CHCl3). Source: Soft coral Sinularia lochmodes (northern coast of Taiwan). Pharm: Anti-inflammatory (LPS-stimulated RAW264.7 macrophages, inhibits accumulation of COX-2 protein, 10 μmol/L, reduces level of COX-2 to (61.0 ± 6.0)%, 100 μmol/L, to (32.8 ± 3.2)%). Ref: Y. -J. Tseng, et al, Mar. Drugs, 2012, 10, 1572

2.19 Valerenane Sesquiterpenoids

77

OH O

HO H

242 Lochmolin D Type: Aromadendrane sesquiterpenoids. C15H24O3 Colorless oil, [α]D26 = −66° (c = 2.0, CHCl3). Source: Soft coral Sinularia lochmodes (northern coast of Taiwan). Pharm: Anti-inflammatory (LPS-stimulated RAW264.7 macrophages, inhibits accumulation of COX-2 protein, 100 μmol/L, reduces level of COX-2 to (71.3 ± 7.2)%). Ref: Y. -J. Tseng, et al, Mar. Drugs, 2012, 10, 1572 HO

O

HO H

243 Spathulenol‡ (1α,4β,5β,6α,7α)-10 (14)-Aromadendren-4-ol Type: Aromadendrane sesquiterpenoids. C15H24O Oil, [α]D = +56°. Source: Soft coral Sinularia kavarattiensis. Pharm: Antifeedant and insect repellant; antifungal; anti-infective. Ref: T. D. Hubert, et al, Phytochemistry, 1985, 24, 1197│V. T. Goud, et al, Biochem. Syst. Ecol., 2002, 30, 493 H

HO

H

2.19 Valerenane Sesquiterpenoids 244 Sinularianin C Type: Valerenane sesquiterpenoids. C16H22O4 Source: Soft coral Sinularia sp. (Dongluo I., Hainan Province, China). Pharm: NF-κB inhibitor (mild). Ref: B. Yang, et al, Mar. Drugs, 2013, 11, 4741

78

2 Sesquiterpenoids

O

H

O

O

O

H

245 Sinularianin D Type: Valerenane sesquiterpenoids. C15H22O3 Source: Soft coral Sinularia sp. (Dongluo I., Hainan Province, China). Pharm: NF-κB inhibitor (mild). Ref: B. Yang, et al, Mar. Drugs, 2013, 11, 4741 O

O

H

O

H

2.20 Illudalane Sesquiterpenoids 246 Alcyopterosin A 4-Chloro-2,6,8-illudalatriene Type: Illudalane sesquiterpenoids. C15H21Cl Oil. Source: Soft coral Alcyonium paessleri (psychrophilic, cold water, near South Georgia I.). Pharm: Cytotoxic (Hep2, IC50 = 13.5 μmol/L; HT29, IC50 = 10 μg/mL). Ref: J. A. Palermo, et al, JOC, 2000, 65, 4482│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev) 14 10

Cl 15

247 Alcyopterosin C Type: Illudalane sesquiterpenoids. C15H19NO4 Cryst. (MeOH), mp 83–84 °C. Source: Soft coral Alcyonium paessleri (psychrophilic, cold water, near South Georgia I.). Pharm: Cytotoxic (Hep2, IC50 = 13.5 μmol/L; HT29, IC50 = 10 μg/mL). Ref: J. A. Palermo, et al, JOC, 2000, 65, 4482│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)

2.21 Furodysinin Sesquiterpenoids

79

O O N

O

O

248 Alcyopterosin E Type: Illudalane sesquiterpenoids. C15H17NO5 Oil, [α]D25 = −31.28° (c = 2.35, CHCl3). Source: Soft coral Alcyonium paessleri (psychrophilic, cold water, near South Georgia I.). Pharm: Cytotoxic (Hep2, IC50 = 13.5 μmol/L). Ref: J. A. Palermo, et al, JOC, 2000, 65, 4482│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)

O O

N O

O

O

249 Alcyopterosin H Type: Illudalane sesquiterpenoids. C15H21NO4 Oil, [α]D25 = −13.9° (c = 1.05, CHCl3). Source: Soft coral Alcyonium paessleri (psychrophilic, cold water, near South Georgia I.). Pharm: Cytotoxic (Hep2, IC50 = 13.5 μmol/L; HT29, IC50 = 10 μg/mL). Ref: J. A. Palermo, et al, JOC, 2000, 65, 4482│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev) HO H O O

N

O

2.21 Furodysinin Sesquiterpenoids 250 14-Acetylthioxyfurodysinin lactone Type: Furodysinin sesquiterpenoids. C17H22O4S Cryst., mp 144–145 °C, [α]D = −178° (CHCl3). Source: Sponges Dysidea herbacea and Dysidea sp. Pharm: LTB4 receptor partial agonist. Ref: B. Carté, et al, Tet. Lett., 1989, 30, 2725 O

H

14

OH O

S

O

8

H

80

2 Sesquiterpenoids

251 9,10-Dehydrofurodysinin Type: Furodysinin sesquiterpenoids. C15H18O Oil, [α]D25 = +259° (c = 0.22, CHCl3). Source: Nudibranch Hypselodoris webbi. Pharm: Toxic (brine shrimp); antifeedant, ichthyotoxin. Ref: A. Fontana, et al, JNP, 1994, 57, 510 H O

H

2.22 Chamigrane Sesquiterpenoids 252 10-Bromo-2,7(14)-chamigradiene Type: Chamigrane sesquiterpenoids. C15H23Br Oil. Source: Red alga Laurencia rigida (Australia). Pharm: Antifoulant. Ref: G. M. König, et al, JNP, 1997, 60, 967 Br

253 10-Bromo-1,7(14)-chamigradiene-3,9-diol Type: Chamigrane sesquiterpenoids. C15H23BrO2 Oil, [α]D25 = −6.5° (c = 1.37, CHCl3). Source: Red alga Laurencia rigida (Australia). Pharm: Antifoulant. Ref: G. M. König, et al, JNP, 1997, 60, 967 HO Br OH

254 10-Bromo-2,7-chamigradien-9-ol Type: Chamigrane sesquiterpenoids. C15H23BrO [α]D25 = −49.4° (c = 0.95, CHCl3). Source: Red alga Laurencia rigida (Australia). Pharm: Antifoulant. Ref: G. M. König, et al, JNP, 1997, 60, 967 Br HO

2.22 Chamigrane Sesquiterpenoids

81

255 10-Bromo-7α,8α-epoxychamigr-1-en-3-ol Type: Chamigrane sesquiterpenoids. C15H23BrO2 Colorless oil, [α]D24 = −13.9° (c = 0.15, CHCl3). Source: Red alga Laurencia okamurai (Rongcheng, China). Pharm: Toxic (brine shrimp). Ref: X. -D. Li, et al, Fitoterapia, 2012, 83, 518 OH Br

O

256 (6R,9R,10S)-10-Bromo-9-hydroxy-chamigra-2,7(14)-diene Type: Chamigrane sesquiterpenoids. C15H23BrO Oil, [α]D25 = −110° (c = 0.20, CHCl3). Source: Red alga Laurencia majuscula (Okinawa). Pharm: Antibacterial (paper disc diffusion assay, Alcaligenes aquamarinus, Azomonas agilis, Azotobacter beijerinckii, Erwinia amylovora, and Escherichia coli, MIC = 10–30 μg/disc). Ref: C. S. Vairappan, et al, Phytochemistry, 2001, 58, 517 HO Br

257 Cartilagineol Alloisoobtusol Type: Chamigrane sesquiterpenoids. C15H23Br2ClO Cryst., mp 62–63 °C, [α]D = −32° (c = 0.25, CHCl3). Source: Red alga Laurencia cartilaginea (Hawaii). Pharm: Cytotoxic (P388, IC50 = 5.0 μg/mL, A549, IC50 = 1.0 μg/mL, HT29, IC50 = 0.25 μg/mL, MEL28, IC50 = 1.0 μg/mL). Ref: E. G. Juagdan, et al, Tetrahedron, 1997, 53, 521│G. Guella, et al, Tet. Lett., 1997, 38, 8261│M. E. Y. Francisco, et al, Tet. Lett., 1998, 39, 5289│M. Wessels, et al, JNP, 2000, 63, 920 Br HO

9 10

Br 6

2 3

Cl

258 Chamigrane epoxide Type: Chamigrane sesquiterpenoids. C15H23Br2ClO Cryst., mp 123.5–124 °C, [α]D24 = +13° (c = 0.4, CHCl3). Source: Red algae Laurencia sp. (N. Borneo I., Sabah, Malaysia), Laurencia okamurai and Laurencia pinnatifida. Pharm: Antibacterial (30 mg/disc: Staphylococcus sp., IZD = 9 mm, MIC = 300 μg/mL). Ref: M. Ojika, et al, Phytochemistry, 1982, 21, 2410│S. Bano, et al, PM, 1987, 53, 508│P. J. Cox, et al, Z. Kristallogr., 1989, 188, 1│C. S. Vairappan, et al, Mar. Drugs, 2010, 8, 1743

82

2 Sesquiterpenoids

Br

Cl Br O

259 Dechloroelatol Type: Chamigrane sesquiterpenoids. C15H23BrO Oil. Source: Red alga Laurencia rigida. Pharm: Antimycobacterial. Ref: A. G. González, et al, Tet. Lett., 1976, 17, 3051 Br HO

260 Deoxyprepacifenol Type: Chamigrane sesquiterpenoids. C15H21Br2ClO Cryst. (pentane), mp 125 °C. Source: Red algae Laurencia claviformis, Laurencia nipponica, Laurencia elata, Laurencia marianensis (Great Barrier Reef, 146°50´E 18°00´S) and Laurencia majuscula, sea hare Aplysia californica. Pharm: Insecticide. Ref: C. Ireland, et al, JOC, 1976, 41, 2461│F. R. Fronczek, et al, Acta Cryst., Sect. C, 1989, 45, 1102│R. de Nys, et al, Aust. J. Chem., 1993, 46, 933 Br

5

O Br

Cl

261 (E)-9,15-Dibromo-1,3(15)-chamigradien-7-ol Type: Chamigrane sesquiterpenoids. C15H22Br2O Cryst., mp 84–86°, [α]D = −64° (c = 0.29, CHCl3). Source: Sea hare Aplysia dactylomela (Canary Is., Spain, 14 °10’W 28 °30’N). Pharm: Antibacterial; antifungal; algicide; toxic (brine shrimp). Ref: A. G. González, et al, Tet. Lett., 1983, 24, 847 Br

HO Br

2.22 Chamigrane Sesquiterpenoids

83

262 (3(15)Z,6S,9S,10R)-10,15-Dibromo-1,3(15),7(14)-chamigratrien-9-ol Type: Chamigrane sesquiterpenoids. C15H20Br2O Oil, [α]D = +2.7° (c = 0.002, CHCl3). Source: Red algae Laurencia majuscula and Laurencia chondrioides. Pharm: Cytotoxic (PS cells, ED50 = 40 μg/mL). Ref: F. J. Schmitz, et al, JACS, 1982, 104, 6415│J. C. Coll, et al, Aust. J. Chem., 1989, 42, 1591; 1992, 45, 1611│A. Bansemir, et al, Chem. Biodiversity, 2004, 1, 463 Br 10R

HO 9S

6S 3

H Br

263 (3(15)E,6S,9S,10R)-10,15-Dibromo-1,3(15),7(14)-chamigratrien-9-ol Type: Chamigrane sesquiterpenoids. C15H20Br2O Oil, [α]D = −40° (c = 0.01, CHCl3). Source: Red alga Laurencia majuscula, sea hare Aplysia dactylomela (shallow waters, near La Parguera, Puerto Rico). Pharm: Cytotoxic (PS cells, ED50 = 50 μg/mL). Ref: M. Suzuki, et al, Tet. Lett., 1978, 4805│F. J. Schmitz, et al, JACS, 1982, 104, 6415│J. C. Coll, et al, Aust. J. Chem., 1989, 42, 1591; 1992, 45, 1611 Br 10R

HO 9S

6S 3

Br H

264 4,10-Dibromo-3-chloro-7,9-chamigradien-1-ol Type: Chamigrane sesquiterpenoids. C15H21Br2ClO Oil, [α]D = −36° (c = 0.12, CHCl3). Source: Red alga Laurencia nidifica (Oahu). Pharm: Antiviral (HSV, IC50 > 100 μg/mL). Ref: J. Kimura, et al, Bull. Chem. Soc. Jpn., 1999, 72, 289 Br OH

Cl Br

265 2,10-Dibromo-3-chloro-7,8:9,10-diepoxychamigrane Type: Chamigrane sesquiterpenoids. C15H21Br2ClO2 Oil, [α]D = +91° (c = 0.05, CHCl3). Source: Red alga Laurencia nidifica (Oahu), sea hare Aplysia dactylomela (Brazil).

84

2 Sesquiterpenoids

Pharm: Antiviral (HSV, IC50 = 130 μg/mL). Ref: C. R. Kaiser, et al, Spectrosc. Lett., 1998, 31, 573│J. Kimura, et al, Bull. Chem. Soc. Jpn., 1999, 72, 289

Br

Cl Br

O O

266 Elatol 10-Bromo-2-chloro-2,7(14)-chamigradien-9-ol Type: Chamigrane sesquiterpenoids. C15H22BrClO Oil, [α]D = +83.5° (c = 0.365, MeOH). Source: Red algae Laurencia elata, Laurencia scoparia, Laurencia rigida, Laurencia chondrioides and Laurencia cartilaginea, sea hare Aplysia dactylomela (shallow waters, near La Parguera, Puerto Rico). Pharm: Cytotoxic (PS cells, ED50 = 26 μg/mL); antimycobacterial; antifeedant; antimutagenic; antifoulant. Ref: J. J. Sims, et al, Tet. Lett., 1974, 3487│F. J. Schmitz, et al, JACS, 1982, 104, 6415│G. M. König, et al, PM, 2000, 66, 337 Br HO Cl

267 Isoobtusol Type: Chamigrane sesquiterpenoids. C15H23Br2ClO Cryst., mp 118–120 °C, [α]D = +33°. Source: Red alga Laurencia obtusa, sea hare Aplysia dactylomela Pharm: Toxic (brine shrimp). Ref: A. G. González, et al, Tet. Lett., 1976, 17, 3051; 1979, 20, 2717; 2719│M. Wessels, et al, JNP, 2000, 63, 920 Br HO Cl Br

268 Isoobtusol acetate Acetylisoobtusol Type: Chamigrane sesquiterpenoids. C17H25Br2ClO2 [α]D = +57.9° (c = 0.38, CHCl3). Source: Sea hare Aplysia dactylomela (shallow waters, near La Parguera, Puerto Rico). Pharm: Cytotoxic (PS cells, ED50 = 40 μg/mL). Ref: F. J. Schmitz, et al, JACS, 1982, 104, 6415

2.22 Chamigrane Sesquiterpenoids

85

Br O Cl

O

Br

269 Isorigidol 10S-Bromo-1,7(14)-chamigradiene-3,9-diol Type: Chamigrane sesquiterpenoids. C15H23BrO2 Cryst., mp 138–140 °C, [α]D25 = −115° (c = 0.32, CH2Cl2). Source: Red alga Laurencia scoparia (Brazil). Pharm: Anthelmintic (in vitro, parasitant stage of Nippostrongylus brasiliensis, moderate). Ref: D. Davyt, et al, JNP, 2001, 64, 1552│L. Suescun, et al, Acta Crystallogr. Sect. C. Cryst Struct. Commun., 2001, 57, 286 Br HO

10

OH

270 Laurecomin B Type: Chamigrane sesquiterpenoids. C15H23BrO Source: Red alga Laurencia composita (Pingtan I., Fujian, China). Pharm: Antifungal. Ref: X. -D. Li, et al, Fitoterapia, 2012, 83, 1191 OH Br

271 (6S,9R,10S)-Ma’ilione Type: Chamigrane sesquiterpenoids. C14H19BrO2 mp 135–136 °C, [α]D = −20° (c = 0.196, CHCl3). Source: Red alga Laurencia cartilaginea (Hawaii). Pharm: Cytotoxic (P388, IC50 = 5.0 μg/mL, A549, IC50 = 5.0 μg/mL, HT29, IC50 = 0.5 μg/mL, MEL28, IC50 = 10.0 μg/mL); anthelmintic (parasitant stage of Nippostrongylus brasiliensis, moderate in vitro). Ref: G. Guella, et al, Tet. Lett., 1997, 38, 8261│E. G. Juagdan, et al, Tetrahedron, 1997, 53, 521│M. E. Y. Francisco, et al, Tet. Lett., 1998, 39, 5289│D. Davyt, et al, JNP, 2001, 64, 1552│L. Suescun, et al, Acta Crystallogr. Sect. C. Cryst Struct. Commun., 2001, 57, 286 O Br

HO

86

2 Sesquiterpenoids

272 Mailiohydrin Type: Chamigrane sesquiterpenoids. C15H22Br2O2 Oil, [α]D = −9.6° (c = 0.26, CHCl3). Source: Red alga Laurencia sp. (Philippines). Pharm: Cytotoxic (NCI 60-cell line hmn tumour screen, potent activity against NCI/ADR-Res breast carcinoma cell line). Ref: M. E. Y. Francisco, et al, JNP, 2001, 64, 790 HO Br Br OH

273 Obtusol 3,10-Dibromo-2-chloro-7(14)-chamigren-9-ol Type: Chamigrane sesquiterpenoids. C15H23Br2ClO Cryst., mp 145–146 °C, [α]D = +14.3° (c = 0.38, CHCl3). Source: Red alga Laurencia obtusa, sea hare Aplysia dactylomela. Pharm: Antifungal, algicide; antimutagenic. Ref: A. G. González, et al, Tet. Lett., 1976, 17, 3051; 1979, 20, 2717; 2719│M. Wessels, et al, JNP, 2000, 63, 920 Br HO

Br

Cl

274 Pacifenol Type: Chamigrane sesquiterpenoids. C15H21Br2ClO2 Cryst. (petrol), mp 149–150.5 °C. Source: Red algae Laurencia pacifica, Laurencia majuscula, Laurencia nidifica, Laurencia claviformis and Laurencia marianensis, sea hare Aplysia dactylomela. Pharm: Antifeedant (aphids); insecticide; antimitotic. Ref: J. J. Sims, et al, JACS, 1971, 93, 3774│T. Suzuki, Chem. Lett., 1980, 541│R. de Nys, et al, Aust. J. Chem., 1993, 46, 933│C. R. Kaiser, et al, Magn. Reson. Chem., 2001, 39, 147 Br

O

OH

Cl Br

275 Steperoxide B Merulin A Type: Chamigrane sesquiterpenoids. C14H22O4 Cryst., mp 214–217 °C, mp 210–212 °C, [α]D25 = +239° (c = 0.1, MeOH), [α]D27 = +194° (c = 0.16, MeOH). Source:

2.22 Chamigrane Sesquiterpenoids

87

Mangrove-derived fungus Talaromyces flavus from mangrove Sonneratia apetala (Hainan Is, China), mangrove Xylocarpus granatum. Pharm: Cytotoxic (MCF7, IC50 = 4.17 μg/mL, control Epirubicin (EPI), IC50 = 0.56 μg/mL; MDA-MB-435, IC50 = 1.90 μg/mL, EPI, IC50 = 0.33 μg/mL; HepG2, IC50 = 6.79 μg/mL, EPI, IC50 = 0.56 μg/mL; HeLa, IC50 = 7.97 μg/mL, EPI, IC50 = 0.51 μg/mL; PC3, IC50 = 1.82 μg/mL, EPI, IC50 = 0.16 μg/mL). Ref: S. Chokpaiboon, et al, JNP, 2010, 73, 1005│D. -Z. Liu, et al, Tet. Lett., 2010, 51, 3152│H. Li, et al, JNP, 2011, 74, 1230 O O

O OH

276 Talaperoxide A Type: Chamigrane sesquiterpenoids. C12H24O5 Colorless crystals (MeOH), mp 125–127°C, [α]D25 = +191° (c = 0.11, MeOH). Source: Mangrove-derived fungus Talaromyces flavus from mangrove Sonneratia apetala (Hainan Is, China). Pharm: Cytotoxic (MCF7, IC50 = 19.77 μg/mL, control Epirubicin (EPI), IC50 = 0.56 μg/mL; MDA-MB-435, IC50 = 11.78 μg/mL, EPI, IC50 = 0.33 μg/mL; HepG2, IC50 = 12.93 μg/mL, EPI, IC50 = 0.56 μg/mL; HeLa, IC50 = 13.7 μg/mL, EPI, IC50 = 0.51 μg/mL; PC3, IC50 = 5.70 μg/ mL, EPI, IC50 = 0.16 μg/mL). Ref: H. Li, et al, JNP, 2011, 74, 1230 O O

O O

O

277 Talaperoxide B Type: Chamigrane sesquiterpenoids. C12H24O5 Colorless crystals (MeOH), mp 91–93 °C, [α]D25 = +261° (c = 0.07, MeOH). Source: Mangrove-derived fungus Talaromyces flavus from mangrove Sonneratia apetala (Hainan Is, China). Pharm: Cytotoxic (MCF7, IC50 = 1.33 μg/mL, control Epirubicin (EPI), IC50 = 0.56 μg/mL; MDA-MB-435, IC50 = 2.78 μg/mL, EPI, IC50 = 0.33 μg/mL; HepG2, IC50 = 1.29 μg/mL, EPI, IC50 = 0.56 μg/mL; HeLa, IC50 = 1.73 μg/mL, EPI, IC50 = 0.51 μg/mL; PC3, IC50 = 0.89 μg/mL, EPI, IC50 = 0.16 μg/mL). Ref: H. Li, et al, JNP, 2011, 74, 1230 O O

O O

O

88

2 Sesquiterpenoids

278 Talaperoxide C Type: Chamigrane sesquiterpenoids. C14H20O4 White solid, mp 148–150 °C, [α]D25 = +225° (c = 0.12, MeOH). Source: Mangrove-derived fungus Talaromyces flavus from mangrove Sonneratia apetala (Hainan Is, China). Pharm: Cytotoxic (MCF7, IC50 = 6.63 μg/mL, control Epirubicin (EPI), IC50 = 0.56 μg/mL; MDA-MB-435, IC50 = 2.64 μg/mL, EPI, IC50 = 0.33 μg/mL; HepG2, IC50 = 15.11 μg/mL, EPI, IC50 = 0.56 μg/mL; HeLa, IC50 = 12.71 μg/mL, EPI, IC50 = 0.51 μg/mL; PC3, IC50 = 4.34 μg/mL, EPI, IC50 = 0.16 μg/mL). Ref: H. Li, et al, JNP, 2011, 74, 1230 O O

O

O

279 Talaperoxide D Type: Chamigrane sesquiterpenoids. C14H20O4 White solid, mp 120–122 °C, [α]D25 = +126° (c = 0.08, MeOH). Source: Mangrove-derived fungus Talaromyces flavus from mangrove Sonneratia apetala (Hainan Is, China). Pharm: Cytotoxic (MCF7, IC50 = 1.92 μg/mL, control Epirubicin (EPI), IC50 = 0.56 μg/mL; MDA-MB-435, IC50 = 0.91 μg/mL, EPI, IC50 = 0.33 μg/mL; HepG2, IC50 = 0.90 μg/mL, EPI, IC50 = 0.56 μg/mL; HeLa, IC50 = 1.31 μg/mL, EPI, IC50 = 0.51 μg/mL; PC3, IC50 = 0.70 μg/mL, EPI, IC50 = 0.16 μg/mL). Ref: H. Li, et al, JNP, 2011, 74, 1230 O O

O

O

2.23 Sativane Sesquiterpenoids 280 Drechslerine D Type: Sativane sesquiterpenoids. C15H22O3 Oil, [α]D22 = −90° (c = 0.4, EtOH). Source: Marine-derived fungus Drechslera dematioidea from red alga Liagora viscida (inner tissue). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 ≤ 5.1 μg/mL). Ref: C. Osterhage, et al, JNP, 2002, 65, 306

2.24 Other Bicyclic Sesquiterpenoids

89

OH

O 15

O

281 Drechslerine G Type: Sativane sesquiterpenoids. C15H24O3 Oil, [α]D22 = −7.2° (c = 0.47, EtOH). Source: Marine-derived fungus Drechslera dematioidea from red alga Liagora viscida (inner tissue). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 ≤ 5.1 μg/ mL). Ref: C. Osterhage, et al, JNP, 2002, 65, 306

O

O OH

2.24 Other Bicyclic Sesquiterpenoids 282 Erectathiol Type: Bulgarane sesquiterpenoids. C15H22S Oil, [α]D24 = +23° (c = 0.4, CHCl3). Source: Soft coral Nephthea erecta (Green I., Taiwan). Pharm: Anti-inflammatory (10 μgmol/L, reduced level of iNOS protein (58.0 ± 6.5)%, reduced level of COX-2 protein (108.7 ± 4.5)%); antibacterial. (166 μg/disk: Enterobacter aerogenes ATCC13048, Serratia marcescens ATCC25419, Yersinia enterocolitica ATCC23715, and Shigella sonnei ATCC11060, moderate; Salmonella enteritidis ATCC13076, greater potential than control Ampicillin). Ref: S. -Y. Cheng, et al, Tet. Lett., 2009, 50, 802

HS

283 Peribysin E Type: Fukinane sesquiterpenoids. C16H26O4 Pale yellow oil, [α]D = −262.2° (c = 0.11, EtOH). Source: Marine-derived fungus Periconia byssoides OUPS-N133.

90

2 Sesquiterpenoids

Pharm: Cell-adhesion inhibitor. Ref: T. Yamada, et al, J. Antibiot., 2005, 58, 185│A. R. Angeles, et al, JACS, 2008, 130, 13765 O

H

HO

O

OH

284 Picrotin Type: Picrotoxane sesquiterpenoids. C15H18O7 Cryst. (H2O), mp 255 °C, [α]D16 = −70° (EtOH). Source: Sponge Spirastrella inconstans. Pharm: GABAA receptor antagonist; convulstant (less active than Picrotoxinin). Ref: N. S. Sarma, et al, Ind. J. Chem., Sect. B, 1987, 26, 189│C. H. Jarboe, et al, JMC, 1968, 11, 729 O O O

O O

OH

OH

285 Picrotoxinin Type: Picrotoxane sesquiterpenoids. C15H16O6 Cryst. (H2O), mp 209.5 °C, [α]D = −5.85° (c = 3.65, CHCl3). Source: Sponge Spirastrella inconstans. Pharm: Ichthyotoxin; potent convulsant drug; LD50 (mus, ipr) = 3 mg/kg. Ref: N. S. Sarma, et al, Ind. J. Chem., Sect. B, 1987, 26, 189 O O O

O O

OH

286 Pacifigorgiol Type: Pacifigorgiane sesquiterpenoids. C15H26O Oil, [α]D = +41° (c = 1.02, CHCl3). Source: Gorgonian Pacifigorgia cf. adamsii. Pharm: Ichthyotoxin. Ref: R. R. Izac, et al, Tet. Lett., 1982, 23, 3743│R. R. Izac, et al, Tetrahedron, 1982, 38, 301 H

HO

2.24 Other Bicyclic Sesquiterpenoids

91

287 Pannosane Type: Miscellaneous Spirosesquiterpenoids. C15H24BrClO Oil, [α]D23 = −6.41° (c = 0.53, CHCl3). Source: Red alga Laurencia pannosa (Malaysia). Pharm: Antibacterial (Chromobacterium violaceum, MIC = 60 μg/disk). Ref: M. Suzuki, et al, JNP, 2001, 64, 597

O

Br Cl

288 Pannosanol Type: Miscellaneous Spirosesquiterpenoids. C15H24BrClO Oil, [α]D24 = +4.97° (c = 0.52, CHCl3). Source: Red alga Laurencia pannosa (Malaysia). Pharm: Antibacterial (Proteus mirabilis, MIC = 60 μg/disk; Chromobacterium violaceum and Vibrio cholera, MIC = 100 μg/disk). Ref: M. Suzuki, et al, JNP, 2001, 64, 597 OH Br Cl

289 Aignopsanoic acid Type: Miscellaneous bicyclic sesquiterpenoids. C15H22O3 Amorph. powder, [α]D23 = +42° (c = 0.14, MeOH). Source: Sponge Cacospongia mycofijiensis (Kimbe Bay, Papua New Guinea). Pharm: Antitrypanosomal (Trypanosoma brucei, moderate). Ref: T. A. Johnson, et al, Org. Lett., 2009, 11, 1975 O

COOH

290 Aignopsanoic acid methyl ester Type: Miscellaneous bicyclic sesquiterpenoids. C16H24O3 Amorph. powder, [α]D23 = −60.4° (c = 0.09, MeOH). Source: Sponge Cacospongia mycofijiensis (Kimbe Bay, Papua New Guinea). Pharm: Antitrypanosomal (Trypanosoma brucei, moderate). Ref: T. A. Johnson, et al, Org. Lett., 2009, 11, 1975

92

2 Sesquiterpenoids

O

O

O

H

10Z

291 8,11-Dihydro-12-hydroxy isolaurene Type: Miscellaneous bicyclic sesquiterpenoids. C15H22O Colorless oil, [α]D = +11.5° (c = 0.01, CHCl3). Source: Red alga Laurencia obtusa (Jiddah, Saudi Arabia). Pharm: Antibacterial (gram-positive Bacillus subtilis ATCC 6633, MIC = 39 μg/mL; grampositive Staphylococcus aureus ATCC 29213, MIC = 31 μg/mL); antifungal (Candida albicans, MIC = 120 μg/mL, Aspergillus fumigatus, MIC = 200 μg/mL, Aspergillus flavus, MIC = 1250 μg/mL); cytotoxic (Ehrlich Ascites Carcinoma (EAC), viability of cells used in control experiments exceeded 95%, cytotoxic activity 79.9%). Ref: W. M. Alarif, et al, EurJMC, 2012, 55, 462

HO

292 (–)12,13-Dihydro-14-methoxy-14-deacetoxyspirodysin Type: Miscellaneous bicyclic sesquiterpenoids. C16H26O2 Oil, [α]D25 = +195° (c = 1, CHCl3). Source: Sponge Dysidea fragilis (India waters). Pharm: Antifungal (Candida albicans). Ref: N. S. Reddy, et al, Ind. J. Chem., Sect. B, 1999, 38, 1002 O

H

O

H

293 Epoxyrarisetenolide Type: Miscellaneous bicyclic sesquiterpenoids. C15H20O3 [α]D20 = −52° (c = 0.24, MeOH). Source: Protist ciliate Euplotes rariseta. Pharm: Defensive agent. Ref: G. Guella, et al, Helv. Chim. Acta, 1996, 79, 2180 H H 10

O H

O

11

12

O

2.24 Other Bicyclic Sesquiterpenoids

93

294 Hamigeran L Type: Miscellaneous bicyclic sesquiterpenoids. C20H27BrO5 Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand). Pharm: Cytotoxic (HL60, IC50 = (78.3 ± 0.5)μmol/L). Ref: A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 OH

O

Br

OH

O OH

295 Hamigeran L methyl ester Type: Miscellaneous bicyclic sesquiterpenoids. C21H29BrO5 Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand). Pharm: Cytotoxic (HL60, IC50 = (21.1 ± 0.3)μmol/L). Ref: A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 OH Br

O OH

O O

296 γ-Hydroxybutenolide Type: Miscellaneous bicyclic sesquiterpenoids. C15H20O3 Solid, [α]D24 = +0.23° (c = 0.35, MeOH). Source: Sponge Dysidea herbacea (Palau, Oceania). Pharm: Antifoulant (blue mussels Mytilus edulis and Mytilus galloprovincialis). Ref: Y. Seta, et al, JNP, 1999, 62. 39

HO

O

O

297 12-Hydroxy isolaurene Type: Miscellaneous bicyclic sesquiterpenoids. C15H20O Colorless oil, [α]D = +41.7° (c = 0.01, CHCl3). Source: Red alga Laurencia obtusa (Jiddah, Saudi Arabia). Pharm: Antibacterial (gram-positive Bacillus subtilis ATCC 6633, MIC = 46 μg/mL; gram-positive Staphylococcus aureus ATCC 29213, MIC = 52 μg/mL); antifungal (Candida albicans, MIC = 2000 μg/mL, Aspergillus fumigatus, MIC = 2000 μg/mL, Aspergillus flavus, MIC = 5000 μg/mL). Ref: W. M. Alarif, et al, EurJMC, 2012, 55, 462

94

2 Sesquiterpenoids

HO

298 Isishippuric acid B Type: Miscellaneous bicyclic sesquiterpenoids. C14H22O4 Powder, mp > 300 °C, [α]D25 = −115° (c = 1, CHCl3). Source: Gorgonian Isis hippuris. Pharm: Cytotoxic (P388, A549, HT29, all ED50S < 0.1 μg/mL). Ref: J. -H. Sheu, et al, Tet. Lett., 2004, 45, 6413

OH O O

OH

299 Isolauraldehyde Type: Miscellaneous bicyclic sesquiterpenoids. C15H18O Colorless oil, [α]D = +11.5° (c = 0.01, CHCl3). Source: Red alga Laurencia obtusa (Jiddah, Saudi Arabia). Pharm: Antibacterial (gram-positive Bacillus subtilis ATCC 6633, MIC = 35 μg/mL; gram-positive Staphylococcus aureus ATCC 29213, MIC = 27 μg/mL); antifungal (Candida albicans, MIC = 70 μg/mL, Aspergillus fumigatus, MIC = 100 μg/mL, Aspergillus flavus, MIC = 1000 μg/mL); cytotoxic (Ehrlich Ascites Carcinoma (EAC), viability of cells used in control experiments exceeded 95%, cytotoxic activity 83.1%). Ref: W. M. Alarif, et al, EurJMC, 2012, 55, 462

O H

300 Δ7 (14)-Isonakafuran 9 Type: Miscellaneous bicyclic sesquiterpenoids. C15H20O [α]D25 = +53.7° (c = 0.13, CHCl3). Source: Sponge Dysidea sp. (Great Barrier Reef, 146°50´E 18°00´S). Pharm: Cytotoxic (mus, P388 leukemia cells). Ref: A. E. Flowers, et al, Aust. J. Chem., 1998, 51, 195 O

7

14

2.24 Other Bicyclic Sesquiterpenoids

95

301 Δ7 (14)-Isonakafuran 9 hydroperoxide Type: Miscellaneous bicyclic sesquiterpenoids. C16H24O4 [α]D25 = +46.6° (c = 0.17, CHCl3). Source: Sponge Dysidea sp. (Great Barrier Reef, 146°50´E 18°00´S). Pharm: Cytotoxic (mus, P388 leukemia cells); antifungal (inhibits growth of Trichophyton mentagrophytes). Ref: A. E. Flowers, et al, Aust. J. Chem., 1998, 51, 195 O OH O

O

302 (–)-Microcionin1 Type: Miscellaneous bicyclic sesquiterpenoids. C15H22O Oil, [α]D25 = −61.4° (c = 3.4, CHCl3). Source: Sponge Fasciospongia sp. Pharm: Antibacterial (Micrococcus luteus, MIC = 6 μg/mL). Ref: H. Gaspar, et al, JNP, 2008, 71, 2049 O

4

303 Nakafuran 8 Type: Miscellaneous bicyclic sesquiterpenoids. C15H20O Oil, [α]D25 = +24.2° (c = 2.65, CHCl3). Source: Sponge Dysidea fragilis (Hawaii), nudibranch Chromodoris maridadulis, dorid nudibranches Hypselodoris godeffroyana, Hypselodoris capensis, Hypselodoris californiensis and Hypselodoris ghiselini. Pharm: Antifeedant (fish). Ref: G. Schulte, et al, Helv. Chim. Acta, 1980, 63, 2159│J. E. Hochlowski, et al, JOC, 1982, 47, 88│J. H. Cardellina, et al, JOC, 1988, 53, 882│T. Uyehara, et al, JCS, Perkin I, 1992, 1785

O

304 Nakafuran 9 Type: Miscellaneous bicyclic sesquiterpenoids. C15H20O Oil, [α]D25 = −106° (c = 0.33, CHCl3). Source: Sponge Dysidea fragilis, dorid nudibranches Hypselodoris ghiselini and Hypselodoris godeffoyana, nudibranches Chromodoris maridadilus and Chromodoris capensis. Pharm: Antifeedant (fish). Ref: G. R. Schulte, et al, Helv. Chim. Acta, 1980, 63, 2159│J. E. Hochlowski, et al, JOC, 1982, 47, 88

96

2 Sesquiterpenoids

O

305 Raikovenal Type: Miscellaneous bicyclic sesquiterpenoids. C15H24O2 [α]D20 = −40° (c = 0.1, MeOH). Source: Protist ciliate Euplotes raikovi. Pharm: Cytotoxic. Ref: G. Guella, et al, Chem. Comm., 1994, 2585 O H H 7

OH H

306 Rarisetenolide Type: Miscellaneous bicyclic sesquiterpenoids. C15H20O2 [α]D20 = −54° (c = 0.28, MeOH). Source: Protist ciliates Euplotes rariseta (PBH1, BR1 and GRH5). Pharm: Defensive agent. Ref: G. Guella, et al, Helv. Chim. Acta, 1996, 79, 2180 H O O

H

307 epi-Rarisetenolide Type: Miscellaneous bicyclic sesquiterpenoids. C15H20O2 Source: Protist ciliates Euplotes rariseta (PBH1, BR1 and GRH5). Pharm: Defensive agent. Ref: G. Guella, et al, Helv. Chim. Acta, 1996, 79, 2180 H O 10

O

H

2.26 Capnellane Sesquiterpenoids

97

2.25 Africanane Sesquiterpenoids 308 3(15)-Africanene 9(15)-Africanene Type: Africanane sesquiterpenoids. C15H24 Oil, [α]D24 = +86° (c = 3.7, CHCl3); [α]D28 = +82° (c = 0.23, CHCl3). Source: Soft corals Sinularia leptoclados (Southern India), Sinularia erecta and Sinularia polydactyla. Pharm: Cytotoxic (EAC, DLAT); anti-inflammatory. Ref: Y. Kashman, et al, Experientia, 1980, 36, 891│J. C. Braekman, et al, Experientia, 1980, 36, 893│G. B. S. Reddy, et al, CPB, 1999, 47, 1214 H

H

309 Africanol (2α,3β,6α)-2-Africananol Type: Africanane sesquiterpenoids. C15H26O Cryst., mp 58–60 °C, [α]D = +59.5° (c = 0.5, CHCl3). Source: Soft coral Lemnalia africana. Pharm: Algicide. Ref: B. Tursch, et al, Tet. Lett., 1974, 747│K. Hayasaka, et al, Tet. Lett., 1985, 26, 873│W. Fan, et al, JOC, 1993, 58, 3557 H 6 3

2

OH

2.26 Capnellane Sesquiterpenoids 310 8β-Acetoxycapnell-9 (12)-ene-10α-ol Type: Capnellane sesquiterpenoids. C17H26O3 Source: Soft corals Dendronephthya rubeola and Capnella imbricata (acetone extracts of frish colonies). Pharm: Antiproliferative (L929, GI50 = 20.9 μmol/L, control Doxorubicin, GI50 = 1.2 μmol/ L; K562, GI50 = 67.4 μmol/L, Doxorubicin, GI50 = 1.2 μmol/L); cytotoxic (HeLa, CC50 = 9.4 μmol/L, control Doxorubicin, CC50 = 2.0 μmol/L). Ref: M. Kaisin, et al, Tetrahedron, 1985, 41, 1067│C. -H. Chang, et al, JNP, 2008, 71, 619│D. Grote, et al, Chem. Biodivers., 2008, 5, 1683

98

2 Sesquiterpenoids

O H OH O 10 8

3

H

311 3β-Acetoxycapnellene-8β,10α,14-triol Type: Capnellane sesquiterpenoids. C17H26O5 Yellow oil, [α]D = +39.7° (c = 0.1, CHCl3). Source: Soft corals Dendronephthya rubeola and Capnella imbricata (Indonesia). Pharm: Cytotoxic (HL60, IC50 = 713 μmol/L, K562, IC50 = 24 μmol/L, G402, IC50 = 52 μmol/L, MCF7, IC50 = 1029 μmol/L, A278, IC50 = 32 μmol/L). Ref: M. Kaisin, et al, Tetrahedron, 1985, 41, 1067│L. A. Morris, et al, Tetrahedron, 1998, 54, 12953│D. Grote, et al, Chem. Biodivers., 2008, 5, 1683 HO

H OH OH

O O

H

312 9(12)-Capnellene Type: Capnellane sesquiterpenoids. C15H24 Oil, [α]D20 = −145° (c = 0.4, CHCl3). Source: Soft coral Capnella imbricata. Pharm: Antibacterial; antineoplastic. Ref: V. Singh, et al, JOC, 1998, 63, 4011│E. Ayanoglu, et al, Tet. Lett., 1978, 1671│J. Buckingham (executive editor), et al, Dictionary of Natural Products, 1995, Vol 1, pp846, Champman & Hall. London 12

H

H 9

H

313 Capnell-9 (12)-ene-8β,10α-diol Type: Capnellane sesquiterpenoids. C15H24O2 Cryst. (hexane), [α]D21 = +41° (c = 0.15, CHCl3). Source: Soft corals Dendronephthya rubeola and Capnella imbricata. Pharm: Antiproliferative (L929, GI50 = 6.8 μmol/L, control Doxorubicin, GI50 = 1.2 μmol/L; K562, GI50 = 70.9 μmol/L, Doxorubicin, GI50 = 1.2 μmol/L); cytotoxic (HeLa, CC50 = 7.6 μmol/L, control Doxorubicin, CC50 = 2.0 μmol/L); cytotoxic (HL60, K562, G402, MCF7, A2780, HT115, IC50 = 0.7–93 μmol/L); inhibits interaction of oncogenic transcription factor Myc with its partner protein Max (strong); algicide. Ref: Y. M. Sheikh, et al, Tetrahedron, 1976, 32, 1171│T. C. W.Mak, et al, Zhongshan Daxue

2.26 Capnellane Sesquiterpenoids

99

Xuebao Ziran Kexueban, 1985, 22│L. A. Morris, et al, Tetrahedron, 1998, 54, 12953│D. Grote, et al, Chem. Biodivers., 2008, 5, 1683 OH

H

OH 10

3

8

H

314 9 (12)-Capnellen-8β-ol Type: Capnellane sesquiterpenoids. C15H24O Amorph. powder, [α]D = +19.5° (c = 0.2, CHCl3). Source: Soft corals Dendronephthya rubeola and Capnella imbricata (Indonesia). Pharm: Cytotoxic (HL60, IC50 = 68 μmol/L, K562, IC50 = 4.6 μmol/L, G402, IC50 > 4500 μmol/L, MCF7, IC50 > 4500 μmol/L, HT115, IC50 > 4500 μmol/L, A278, IC50 = 6.6 μmol/L). Ref: L. A. Morris, et al, Tetrahedron, 1998, 54, 12953│D. Grote, et al, Chem. Biodivers., 2008, 5, 1683 H

H

OH 10

3

8

H

315 3α,14-Diacetoxycapnell-9 (12)-ene-8β,10α-diol Type: Capnellane sesquiterpenoids. C19H28O6 Oil, [α]D25 = +2.2° (c = 1.33, CHCl3). Source: Soft corals Capnella imbricata and Dendronephthya rubeola. Pharm: Antiproliferative (L929, GI50 = 126.4 μmol/L, control Doxorubicin, GI50 = 1.2 μmol/L; K562, GI50 = 142.0 μmol/L, Doxorubicin, GI50 = 1.2 μmol/L); cytotoxic (HeLa, CC50 = 142.0 μmol/L, control Doxorubicin, CC50 = 2.0 μmol/L). Ref: M. Kaisin, et al, Tetrahedron, 1985, 41, 1067│D. Grote, et al, Chem. Biodivers., 2008, 5, 1683

O O H OH OH 3

O O

10 8

H

100

2 Sesquiterpenoids

316 3α,8β-Diacetoxycapnell-9(12)-ene-10a-ol Type: Capnellane sesquiterpenoids. C19H28O5 Oil, [α]D25 = +2.2° (c = 1.33, CHCl3). Source: Soft coral Dendronephthya rubeola. Pharm: Antiproliferative (L929, GI50 = 99.1 μmol/L, control Doxorubicin, GI50 = 1.2 μmol/L; K562, GI50 = 62.2 μmol/L, Doxorubicin, GI50 = 1.2 μmol/L); cytotoxic (HeLa, CC50 = 125.0 μmol/L, control Doxorubicin, CC50 = 2.0 μmol/L). Ref: D. Grote, et al, Chem. Biodivers., 2008, 5, 1683 O H OH O 10 8

3

O O

H

317 2α,8β,13-Triacetoxycapnell-9(12)-ene-10α-ol Type: Capnellane sesquiterpenoids. C21H30O7 Oil, [α]D26 = −17° (c = 0.72, CHCl3). Source: Soft coral Dendronephthya rubeola. Pharm: Antiproliferative (L929, GI50 = 126.9 μmol/L, control Doxorubicin, GI50 = 1.2 μmol/L; K562, GI50 = 126.9 μmol/L, Doxorubicin, GI50 = 1.2 μmol/L); cytotoxic (HeLa, CC50 = 126.9 μmol/L, control Doxorubicin, CC50 = 2.0 μmol/L). Ref: D. Grote, et al, Chem. Biodivers., 2008, 5, 1683 O

O H OH O

O

10 8

3

O

H

O

318 3α,8β,14-Triacetoxycapnell-9(12)-ene-10a-ol Type: Capnellane sesquiterpenoids. C21H30O7 Oil, [α]D24 = +1.7° (c = 0.88, CHCl3). Source: Soft coral Dendronephthya rubeola. Pharm: Antiproliferative (L929, GI50 = 126.9 μmol/L, control Doxorubicin, GI50 = 1.2 μmol/L; K562, GI50 = 126.9 μmol/L, Doxorubicin, GI50 = 1.2 μmol/L); cytotoxic (HeLa, CC50 = 126.9 μmol/L, control Doxorubicin, CC50 = 2.0 μmol/L). Ref: D. Grote, et al, Chem. Biodivers., 2008, 5, 1683 O O

O H OH O

3

O O

10 8

H

2.27 Hirsutane Sesquiterpenoids

101

2.27 Hirsutane Sesquiterpenoids 319 Chondrosterin A Type: Hirsutane sesquiterpenoids. C15H20O2 Yellowish oil, [α]D20 = +112° (c = 0.024, MeOH). Source: Marine-derived fungus Chondrostereum sp. from soft coral Sarcophyton tortuosum (Hainan, China). Pharm: Cytotoxic (A549, IC50 = 2.45 μmol/L; CNE2, IC50 = 4.95 μmol/L; LoVo, IC50 = 5.47 μmol/L). Ref: H. -J. Li, et al, Mar. Drugs, 2012, 10, 627 OH

O H

320 ent-Gloeosteretriol Type: Hirsutane sesquiterpenoids. C15H26O3 [α]D25 = −1.5° (c = 1.33, MeOH). Source: An unidentified marine-derived fungus from sponge Haliclona sp. (Indo-pacific). Pharm: Antibacterial (gram-positive Bacillus subtilis). Ref: G. -Y. -S. Wang, et al, Tetrahedron, 1998, 54, 7335 HO

HO

5

7

OH 9

3

1

H

321 Hirsutanol A (2α,10β)-2,10-Dihydroxy-4(15),6,8-hirsutatrien-5-one Type: Hirsutane sesquiterpenoids. C15H18O3 [α]D25 = −23.5° (c = 0.97, MeOH). Source: An unidentified marine-derived fungus from sponge Haliclona sp. Pharm: Inhibits expression of nitric oxide synthase and cyclooxygenase-2; antibacterial (gram-positive Bacillus subtilis). Ref: G. -Y. -S. Wang, et al, Tetrahedron, 1998, 54, 7335 OH

O OH

322 Chondrosterin J Type: Rearranged hirsutane sesquiterpenoids. C15H22O3 Source: Marine-derived fungus Chondrostereum sp. (cultivation in a medium with glycerol as carbon source) from an unidentified soft coral. Pharm: Cytotoxic (HTCLs, potent). Ref: H. -J. Li, et al, Mar. Drugs, 2014, 12, 167

102

2 Sesquiterpenoids

HO

H

H

H HO

O

2.28 Silphiperfoliane Sesquiterpenoids 323 Subergorgic acid 11-Oxo-5-silphiperfolen-13-oic acid Type: Silphiperfoliane sesquiterpenoids. C15H20O3 Cryst., mp 179–180 °C, mp 200–202 °C, [α]D20 = −128° (c = 1, MeOH). Source: Gorgonians Isis hippuris, gorgonian (horny coral) Subergorgia suberosa. Pharm: Cytotoxic (P388, ED50 = 13.3 μg/mL; A549, ED50 > 50 μg/mL; HT29, ED50 > 50 μg/mL); cardiotoxic; neuromuscular transmission inhibitor; LD50 (mus, ivn) = 22.8 mg/kg. Ref: A. Groweiss, et al, Tet. Lett., 1985, 26, 2379│J. -H. Sheu, et al, JNP, 2000, 63, 1603 O O OH

2.29 Quadrane Sesquiterpenoids 324 Quadrone Type: Quadrane sesquiterpenoids. C15H20O3 Cryst. (MeOH), mp 185–186 °C, [α]D18 = −50° (c = 0.1, EtOH). Source: Marine-derived fungus Aspergillus terreus. Pharm: Cytotoxic (NCI’s 60 cell line in vitro screen, weak differential cytotoxity). Ref: R. L. Ranieri, Tet. Lett., 1978, 19, 499│H. R. Bokesch, et al, Tet. Lett., 1996, 37, 3259

H

O O

O

325 Suberosenone Type: Quadrane sesquiterpenoids. C15H22O [α]D = +55.7° (c = 0.78, CHCl3). Source: Gorgonian (horny coral) Subergorgia suberosa. Pharm: Cytotoxic (NCI’s 60 cell line

2.30 Precapnellane Sesquiterpenoids

103

screen in vitro, ovarian, renal and melanoma lines were particularly sensitive). Ref: H. R. Bokesch, et al, Tet. Lett., 1996, 37, 3259│H. -Y. Lee, et al, Org. Lett., 2000, 2, 1951

H 4

O

326 Terrecyclic acid A Type: Quadrane sesquiterpenoids. C15H20O3 Cryst. (hexane/Et2O), mp 177–179 °C, [α]D21 = +33.9° (c = 0.177, CHCl3). Source: Marine-derived fungus Aspergillus terreus. Pharm: Antimicrobial (wide spectrum); antineoplastic; mycotoxin; enzyme inhibitor. Ref: M. Nakagawa, et al, J. Antibiot., 1982, 35, 778│H. R. Bokesch, et al, Tet. Lett., 1996, 37, 3259

H

O O

O

327 Terrecyclol Type: Quadrane sesquiterpenoids. C15H22O2 Oil. Source: Marine-derived fungus Aspergillus terreus. Pharm: Mycotoxin; antibiotic. Ref: M. Nakagawa, et al, Agric. Biol. Chem., 1984, 48, 117│H. R. Bokesch, et al, Tet. Lett., 1996, 37, 3259

H OH O

2.30 Precapnellane Sesquiterpenoids 328 (+)-Dactylol 3-Precapnellen-6β-ol Type: Precapnellane sesquiterpenoids. C15H26O mp 50–51 °C, [α]D24 = +22.5° (c = 1.76, CHCl3). Source: Red alga Laurencia poitei, sea hare Aplysia

104

2 Sesquiterpenoids

dactylomela. Pharm: Inhibits pentobarbital metabolism. Ref: F. J. Schmitz, et al, Tetrahedron, 1978, 34, 2719 OH

H

329 3α,4α-Epoxyprecapnell-9(12)-ene Type: Precapnellane sesquiterpenoids. C15H24O Oil, [α]D24 = +42° (c = 0.57, CHCl3). Source: Soft coral Dendronephthya rubeola. Pharm: Antiproliferative (L929, GI50 = 227.3 μmol/L, control Doxorubicin, GI50 = 1.2 μmol/L; K562, GI50 = 227.3 μmol/L, Doxorubicin, GI50 = 1.2 μmol/L); cytotoxic (HeLa, CC50 = 193.2 μmol/L, control Doxorubicin, CC50 = 2.0 μmol/L). Ref: D. Grote, et al, Chem. Biodivers., 2008, 5, 1683

O

H

2.31 Hamigerane Sesquiterpenoids 330 Debromohamigeran A Type: Hamigerane sesquiterpenoids. C20H26O5 Cryst., mp 88.5–90 °C, [α]D25 = −38.5° (c = 0.11, CH2Cl2). Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand), sponge Hamigera tarangaensis. Pharm: Cytotoxic (HL60, IC50 = (12.5 ± 3.4)μmol/L). Ref: K. D. Wellington, et al, JNP, 2000, 63, 79│K. C. Nicolaou, et al, Angew. Chem., Int. Ed., 2001, 40, 3679│A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 OH

O O

O OH

H

331 Hamigeran A Type: Hamigerane sesquiterpenoids. C20H25BrO5 Yellow needles, mp 207–209 °C, [α]D25 = −22.5° (c = 0.5, CH2Cl2). Source: Sponge Hamigera tarangaensis (Cape

2.31 Hamigerane Sesquiterpenoids

105

Karikari, North I., New Zealand), sponge Hamigera tarangaensis. Pharm: Cytotoxic (HL60, IC50 = (16.0 ± 4.5)μmol/L). Ref: K. D. Wellington, et al, JNP, 2000, 63, 79│K. C. Nicolaou, et al, Angew. Chem., Int. Ed., 2001, 40, 3679│A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 O O

OH Br

O OH

H

332 Hamigeran A ethyl ester Type: Hamigerane sesquiterpenoids. C21H27BrO5 Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand). Pharm: Cytotoxic (HL60). Ref: A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 OH

O

O

Br

O OH

H

333 Hamigeran B Type: Hamigerane sesquiterpenoids. C18H21BrO3 Yellow plates, mp 163–165 °C, [α]D25 = −151° (c = 0.15, CH2Cl2). Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand), sponge Hamigera tarangaensis. Pharm: Cytotoxic (HL60, IC50 = (3.4 ± 0.4)μmol/L). Ref: K. D. Wellington, et al, JNP, 2000, 63, 79│K. C. Nicolaou, et al, Angew. Chem., Int. Ed., 2001, 40, 3679│A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 OH

O

Br

O H 4

106

2 Sesquiterpenoids

334 Hamigeran F Type: Hamigerane sesquiterpenoids. C21H25BrO5 Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand). Pharm: Cytotoxic (HL60, IC50 = (4.9 ± 1.2) μmol/L). Ref: A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 OH HO

O O

Br O H

335 Hamigeran G Type: Hamigerane sesquiterpenoids. C19H23BrO3 Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand). Pharm: Cytotoxic (HL60, IC50 = (2.5 ± 0.2) μmol/L); antifungal (Saccharomyces cerevisiae, mode of action is via influence of Golgi function and Golgi vesicle formation). Ref: A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 OH O

O

Br

H

336 Hamigeran H Type: Hamigerane sesquiterpenoids. C22H30O5 Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand). Pharm: Cytotoxic (HL60, IC50 = (16.5 ± 1.4)μmol/L). Ref: A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 OH

OH O O O

H

337 Hamigeran I Type: Hamigerane sesquiterpenoids. C19H25BrO4 Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand). Pharm: Cytotoxic (HL60, IC50 = (37.2 ± 1.4) μmol/L). Ref: A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041

2.31 Hamigerane Sesquiterpenoids

OH O

107

OH

Br OH H

338 Hamigeran J Type: Hamigerane sesquiterpenoids. C20H25BrO5 Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand). Pharm: Cytotoxic (HL60, IC50 = (48.2 ± 1.2) μmol/L). Ref: A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 O

O OH

OH O

Br

H

339 Hamigeran K Type: Hamigerane sesquiterpenoids. C18H23BrO3 Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand). Pharm: Cytotoxic (HL60, IC50 = (13.7 ± 0.6) μmol/L). Ref: A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 OH

O OH

Br

H

340 10-epi-Hamigeran K Type: Hamigerane sesquiterpenoids. C18H23BrO3 Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand). Pharm: Cytotoxic (HL60, IC50 = (28.5 ± 1.6) μmol/L). Ref: A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 OH

O OH

Br

H

108

2 Sesquiterpenoids

341 4-Bromohamigeran K Type: Hamigerane sesquiterpenoids. C18H22Br2O3 Source: Sponge Hamigera tarangaensis (Cape Karikari, North I., New Zealand). Pharm: Cytotoxic (HL60, IC50 = (5.6 ± 0.4) μmol/L). Ref: A. J. Singh, et al, Org. Biomol. Chem., 2013, 11, 8041 OH

O OH

Br

Br

H

2.32 Miscellaneous Tricyclic Sesquiterpenoids 342 Paesslerin A Type: Miscellaneous tricyclic sesquiterpenoids. C17H26O2 Source: Soft coral Alcyonium paessleri (psychrophilic, cold water, near South Georgia I.). Pharm: Cytotoxic (hmn tumor cell lines, moderate). Ref: M. F. Rodriguez et al, Org. Lett., 2001, 3, 1415│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)

O

O

343 Paesslerin B Type: Miscellaneous tricyclic sesquiterpenoids. C18H26O4 Source: Soft coral Alcyonium paessleri (psychrophilic, cold water, near South Georgia I.). Pharm: Cytotoxic (hmn tumor cell lines, moderate). Ref: M. F. Rodriguez et al, Org. Lett., 2001, 3, 1415│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)

O

O

O O

2.32 Miscellaneous Tricyclic Sesquiterpenoids

109

344 Suberosanone Type: Miscellaneous tricyclic sesquiterpenoids. C15H24O Colorless oil, [α]D25 = −60° (c = 0.1, CHCl3). Source: Gorgonian Isis hippuris. Pharm: Cytotoxic (P388 ED50 = 0.000005 μg/mL, A549 ED50 = 0.036 μg/mL, HT29 ED50 = 0.000005 μg/mL). Ref: J. -H. Sheu, et al, JNP, 2000, 63, 1603

H

O

345 Suberosenol A Type: Miscellaneous tricyclic sesquiterpenoids. C15H24O White powder, mp 106–108 °C, [α]D25 = −232° (c = 0.1, CHCl3). Source: Gorgonian Isis hippuris. Pharm: Cytotoxic (P388 ED50 = 0.000005 μg/mL, A549 ED50 = 0.0051 μg/mL, HT29 ED50 = 0.000005 μg/mL). Ref: J. -H. Sheu, et al, JNP, 2000, 63, 1603

H

HO

H

346 Suberosenol A acetate Type: Miscellaneous tricyclic sesquiterpenoids. C17H26O2 Colorless oil, [α]D25 = −110° (c = 0.1, CHCl3). Source: Gorgonian Isis hippuris. Pharm: Cytotoxic (P388 ED50 = 0.0076 μg/mL, A549 ED50 = 0.08 μg/mL, HT29 ED50 = 0.00036 μg/mL). Ref: J. -H. Sheu, et al, JNP, 2000, 63, 1603

H O O

H

347 Suberosenol B Type: Miscellaneous tricyclic sesquiterpenoids. C15H24O White powder,mp 74–75 °C, [α]D25 = −10° (c = 0.1, CHCl3). Source: Gorgonian Isis hippuris. Pharm: Cytotoxic (P388 ED50 = 0.0000034 μg/mL, A549 ED50 = 0.0002 μg/mL, HT29 ED50 = 0.0000021 μg/ mL). Ref: J. -H. Sheu, et al, JNP, 2000, 63, 1603

110

2 Sesquiterpenoids

H

H

OH

348 Suberosenol B acetate Type: Miscellaneous tricyclic sesquiterpenoids. C17H26O2 Colorless oil, [α]D25 = −8° (c = 0.03, CHCl3). Source: Gorgonian Isis hippuris. Pharm: Cytotoxic (P388 ED50 = 0.074 μg/mL, A549 ED50 = 0.36 μg/mL, HT29 ED50 = 0.005 μg/mL). Ref: J. -H. Sheu, et al, JNP, 2000, 63, 1603

H

H

O O

2.33 Fourcyclic Sesquiterpenoids 349 Cyclosinularane Type: Sinularane sesquiterpenoids. C15H24 Colorless oil, [α]D25 = +22.2° (c = 0.1, CHCl3). Source: Soft coral Sarcophyton acutangulum (Japan waters), stolonifer Clavularia viridis (Japan waters). Pharm: Toxic (brine shrimp assay, LD50 = 4.0 μg/mL). Ref: M. Yasumoto, et al, JNP, 2000, 63, 1534

350 Lemnalol 4(15)-Copaen-3α-ol Type: Copaane sesquiterpenoids. C15H24O Cryst., mp 46–47 °C, [α]D20 = −9.3° (c = 0.01, CHCl3). Source: Soft corals Lemnalia tenuis and Lemnalia

2.33 Fourcyclic Sesquiterpenoids

111

cervicorni. Pharm: Cytotoxic (P388, IC50 = 16.3 μmol/L, control Mithramycin, IC50 = 0.15 μmol/L; HT29, IC50 = 10.5 μmol/L, Mithramycin, IC50 = 0.21 μmol/L). Ref: H. Kikuchi, et al, Tet. Lett., 1982, 23, 1063│H. Kikuchi, et al, CPB, 1983, 31, 1086│C. Y. Duh, et al, JNP, 2004, 67, 1650

HO

H

3 Diterpenoids 3.1 Phytane Diterpenoids 351 Ambliofuran Type: Phytane diterpenoids. C20H30O Oil. Source: Sponge Dysidea amblia (Pt. Loma, California). Pharm: Ichthyotoxin. Ref: R. P. Walker, et al, JOC, 1981, 46, 1098; 1984, 49, 5160 18

19

20

O 1

14

10

6

352 (–)-Bifurcadiol Type: Phytane diterpenoids. C20H34O2 [α]D = −12.47° (c = 9.8, CH2Cl2). Source: Brown alga Bifurcaria bifurcata. Pharm: Cytotoxic (A549, SK-OV-3, SK-MEL-2, XF498 and HCT15 cells, ED50 = 4.1–8.3 μg/mL). Ref: R. Valls,et al, Phytochemistry, 1986, 25, 751│S. Di Guardia, et al, Tet. Lett., 1999, 40, 8359 OH OH

353 Bifurcane Type: Phytane diterpenoids. C20H30O2 Oil, [α]D25 = −7.6° (EtOH). Source: Brown alga Bifurcaria bifurcata (Brittany, France). Pharm: Inhibits the development of fertilized sea urchin eggs. Ref: R. Valls, et al, Phytochemistry, 1995, 39, 145

OH

O

354 Bifurcanol Type: Phytane diterpenoids. C20H34O2 Oil. Source: Brown alga Bifurcaria bifurcata (Morocco). Pharm: Inhibits cell division (in fertilized sea urchin eggs at lower concentration than other linear diterpenes from the same alga). Ref: R. Valls, et al, Phytochemistry, 1993, 34, 1585 OH HO

355 Cacospongionolide C 20-Hydroxy-2-phyten-1,20-olide Type: Phytane diterpenoids. C20H36O3 Oil, [α]D = −18.0° (c = 0.32, CHCl3). Source: Sponge Fasciospongia cavernosa (Adriatic https://doi.org/10.1515/9783110655131-003

114

3 Diterpenoids

Sea). Pharm: Toxic (brine shrimp). Ref: S. De Rosa, et al, JNP, 1995, 58, 1776│S. De Rosa, et al, Tetrahedron, 1995, 51, 10 731 O O

HO

356 Chlorodesmin Type: Phytane diterpenoids. C28H38O9 Oil. Source: Green alga Chlorodesmis fastigiata, sacoglossans Cyerce nigricans and Elysia sp. Pharm: Ichthyotoxic. Ref: R. J. Wells, et al, Experientia, 1979, 35, 1544│V. J. Paul, et al, Bioorg. Mar. Chem., 1987, 1, 1 O

O O

O

O

O O

O O

357 4,9-Diacetoxyudoteal Opuntial Type: Phytane diterpenoids. C28H38O9 Oil, [α]D = −16.6° (c = 2.5, CHCl3). Source: Green algae Halimeda opuntia and Halimeda spp. Pharm: Cytotoxic; antimicrobial. Ref: V. J. Paul, et al, Tetrahedron, 1984, 40, 3053│L. M. V. Tillekeratne, et al, Phytochemistry, 1984, 23, 1331 O O

O

O

O

9

4

O

O

1

O O

358 Eleganolone 1-Hydroxy-2,6,10,14-phytatetraen-13-one Type: Phytane diterpenoids. C20H32O2 Oil. Source: Brown algae Cystoseira balearica and Bifurcaria bifurcata. Pharm: Relaxant; antihypertensive; anticontractive; acetylcholine-histamine antagonist; LD50 (mus, ipr) 100–200 mg/kg. Ref: C, Francisco, et al, Phytochemistry, 1978, 17, 1003│J. F. Biard, et al, Tet. Lett., 1980, 21, 1849│G. Combaut, et al, Phytochemistry, 1981, 20, 2036│J. Li, et al, JNP, 1998, 61, 92│CRC Press, DNP on DVD, 2012, version 20.2

3.1 Phytane Diterpenoids

115

O OH

13

359 Eleganonal 13-Oxo-2,6,10,14-phytatetraen-1-al Type: Phytane diterpenoids. C20H30O2 Source: Brown algae Cystoseira balearica and Bifurcaria bifurcata. Pharm: Antihypertensive; anticontractive; acetylcholine-histamine antagonist; inotropic activity blocker. Ref: C. Francisco, et al, Phytochemistry, 1978, 17, 1003│J. F. Biard, et al, Tet. Lett., 1980, 21, 1849│G. Combaut, et al, Phytochemistry, 1981, 20, 2036│V. Amico, et al, Phytochemistry, 1987, 26, 2637│J. Li, et al, JNP, 1998, 61, 92│CRC Press, DNP on DVD, 2112, version 20.2 O

O

H

360 Epoxyeleganolone 2,3-Epoxy-1-hydroxy-6,10,14-phytatrien-13-one Type: Phytane diterpenoids. C20H32O3 Source: Brown algae Cystoseira balearica and Bifurcaria bifurcata. Pharm: Antihypertensive; anticontractive. Ref: C, Francisco, et al, Phytochemistry, 1978, 17, 1003│J. F. Biard, et al, Tet. Lett., 1980, 21, 1849│G. Combaut, et al, Phytochemistry, 1981, 20, 2036│J. Li, et al, JNP, 1998, 61, 92 O

O OH

361 5-Hydroxygeranyllinalol Type: Phytane diterpenoids. C20H34O2 Gum, [α]D = +17.65° (c = 0.005, hexane). Source: Sponge Myrmekioderma styx (Caribbean Sea). Pharm: Toxic (brine shrimp). Ref: S. Albrizio, et al, Z. Naturforsch, B, Chem. Sci., 1993, 48, 488 OH

OH

362 3-Hydroxy-1,4,6,10-phytatetraen-13-one Type: Phytane diterpenoids. C20H32O2 [α]D25 = +12.3° (c = 0.013, hexane). Source: Sponge Myrmekioderma styx (Bahamas). Pharm: Toxic (brine shrimp). Ref: S. Albrizio, et al, JNP, 1992, 55, 1287 O

OH

116

3 Diterpenoids

363 Malonganenone C Type: Phytane diterpenoids. C21H35NO2 Yellow solid. Source: Gorgonians Leptogorgia gilchristi (near Ponto Malongane, Mozambique) and Euplexaura nuttingi (Pemba I., Tanzania). Pharm: Cytotoxic (anti-oesophageal cancers: WHCO1, IC50 = 57.7 μmol/L; WHCO5, IC50 = 55.7 μmol/L; WHCO6, IC50 = 58.6 μmol/L; KYSE70, IC50 = 55.0 μmol/L; KYSE180, IC50 = 35.5 μmol/L; KYSE520, IC50 > 100.0 μmol/L; MCF12, IC50 > 100.0 μmol/L). Ref: R. A. Keyzers, et al, Tetrahedron, 2006, 62, 2200│H. Sorek, et al, JNP, 2007, 70, 1104 O 5Z

N H O

364 Malonganenone H Type: Phytane diterpenoids. C21H35NO2 Colorless oil. Source: Gorgonian Euplexaura nuttingi (Pemba I., Tanzania). Pharm: Induces apoptosis (transformed mammalian cells, 1.25 μg/mL). Ref: H. Sorek, et al, JNP, 2007, 70, 1104 O

O H

N H

365 1,18-Phytanediyl disulfate Type: Phytane diterpenoids. C20H42O8S2 Amorph. solid, [α]D25 = +7° (c = 0.004, MeOH). Source: Ascidians Sidnyum turbinatum (Mediterranean Sea) and Ascidia mentula (Mediterranean Sea). Pharm: Antiproliferative (in vitro, WEHI-164, IC50 = (300 ± 1) μg/mL, control 6-Mercaptopurine, IC50 = (1.30 ± 0.02)μg/mL); Antiproliferative (IGR-1, IC50 ≈ 140 μg/mL; J774, IC50 ≈ 180 μg/mL; WEHI-164, IC50 ≈ 360 μg/mL; P388, IC50 ≈ 210 μg/mL). Ref: A. Aiello, et al, Tetrahedron, 1997, 53, 5877│A. Aiello, et al, JNP, 2001, 64, 219 OH O

S

O

O

O O

S

OH O

366 (4E,6E,10E)-1,4,6,10,14-Phytapentaen-3-ol Type: Phytane diterpenoids. C20H32O [α]D25 = +13.1° (c = 0.001, hexane). Source: Sponge Myrmekioderma styx (Bahamas). Pharm: Toxic (brine shrimp). Ref: S. Albrizio, et al, JNP, 1992,55,1287

3.1 Phytane Diterpenoids

117

OH

367 Styxenol A Type: Phytane diterpenoids. C20H30O2 [α]D = +15.1° (CH2Cl2), [α]D25 = +13.4° (c = 0.091, hexane). Source: Sponge Myrmekioderma styx (Bahamas). Pharm: Toxic (brine shrimp). Ref: S. Albrizio, et al, JNP, 1992, 55, 1287 OH

O

368 Thuridillin A Type: Phytane diterpenoids. C24H32O8 [α]D25 = −12.5° (c = 0.4, CHCl3). Source: Sacoglossan Thuridilla hopei. Pharm: Defensive secretion. Ref: M. Gavagnin, et al, Gazz. Chim. Ital., 1993, 123, 205 O O O

O

O

O O

O

369 Udoteal Type: Phytane diterpenoids. C24H34O5 Oil. Source: Green algae Udotea flabellum (calcareous, freshly extrated) and Udotea argentea. Pharm: Antifeedant; toxic (marine organisms). Ref: V. J. Paul, et al, Phytochemistry, 1982, 21, 468; 1985, 24, 2239│V. J. Paul, et al, Marine Ecol.: Progr. Ser., 1986, 34, 157│V. J. Paul, et al, Bioorg. Mar. Chem., 1987, 1, 1–29 (rev) O O

O 7

6

O O

118

3 Diterpenoids

370 Verrucosin 4 Type: Phytane diterpenoids. C25H40O5 Oil, [α]D = −9.7° (c = 0.35, CHCl3). Source: Nudibranch Doris verrucosa (Mediterranean Sea). Pharm: PKC activator; tumour promoter. Ref: M. Gavagnin, et al, Tetrahedron, 1997, 53, 1491 O O O OH

O

3.2 10,15-Cyclophytane Diterpenoids 371 Agelasidine B Type: 10,15-Cyclophytane diterpenoids. C23H41N3O2S Syrup (hydrochloride), [α]D25 = −2.5° (c = 0.43, MeOH). Source: Sponge Agelas nakamurai (Okinawa). Pharm: Antispasmodic; antibacterial. Ref: H. Nakamura, et al, JOC, 1985, 50, 2494 H N

NH NH2

O S O

372 (+)-Agelasidine C Type: 10,15-Cyclophytane diterpenoids. C23H41N3O2S Syrup (hydrochloride), [α]D25 = +8.5° (c = 2.0, MeOH) (hydrochloride). Source: Sponges Agelas nakamurai (Okinawa) and Agelas dispar. Pharm: Antispasmodic; antibacterial; NaKATPase inhibitor. Ref: J. J. Morales, et al, JNP, 1992, 55, 389│H. Nakamura, et al, JOC, 1985, 50, 2494│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev) O H2 N

H N

S

O

NH

373 Agelasidine E Type: 10,15-Cyclophytane diterpenoids. C23H41N3O3S Source: Sponge Agelas citrina (Bahamas). Pharm: Antifungal (weak). Ref: E. P. Stout, et al, EurJOC, 2012, 27, 5131

3.2 10,15-Cyclophytane Diterpenoids

119

NH N H

H 2N

O

S

O

OH

374 Agelasidine F Type: 10,15-Cyclophytane diterpenoids. C23H39N3O3S Source: Sponge Agelas citrina (Bahamas). Pharm: Antifungal (weak). Ref: E. P. Stout, et al, EurJOC, 2012, 27, 5131 NH H 2N

N H

O

S

O

O

375 Agelasine E Type: 10,15-Cyclophytane diterpenoids. C26H40N51+ Powder (chloride), mp 180–182 °C (chloride), [α]D23 = −17.1° (c = 1.88, MeOH) (chloride). Source: Sponges Agelas nakamurai (Okinawa) and Agelas sp. (Pacific Ocean). Pharm: Antituberculosis (modest); ATP-ase inhibitor; spasmolytic; antimicrobial. Ref: H. Wu, et al, Tet. Lett., 1984, 25. 3719│H. Wu, et al, Bull. Chem. Soc. Jpn., 1986, 59, 2495│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev)

N H2N

N+ N

N

376 Agelasine F Ageline A Type: 10,15-Cyclophytane diterpenoids. C26H40N51+ Plates (MeCN) or powder (chloride), mp 178–180 °C, [α]D25 = −5.5° (c = 2.5, MeOH), [α]D = −8.4° (c = 3, CHCl3). Source: Sponges Agelas nakamurai (Okinawa), Agelas sp. (Pacific Ocean), Agelas sp. (Baler, Aurora, Philippines) and Agelas sp. (Palau, Western Caroline I., Oceania). Pharm: Antibacterial (Staphylococcus aureus, Bacillus subtilis, 5 μg/disk); antifungal (Aspergillus niger, 100 μg/mL; Saccharomyces cerevisiae, 10 μg/mL; Candida albicans, 5 μg/disk; Candida utilis); ichthyotoxic (lethal to goldfish Carassius auratus); ATPase inhibitor; antituberculosis (inhibits some drug-resistant strains of Mycobacterium tuberculosis and inhibits growth of tuberculosis H37Rv, 3.13 μg/mL). Ref: H. Wu, et al, Tet. Lett., 1984, 25. 3719│R. J. Capon, et al, JACS, 1984, 106, 1819│H. Wu, et al, Bull. Chem. Soc. Jpn., 1986, 59, 2495│G. C. Mangalindan, et al, PM, 2000, 66, 364│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev)

120

3 Diterpenoids

N H 2N

N+ N

N

377 Ambliol A Type: 10,15-Cyclophytane diterpenoids. C20H32O2 Oil, [α]D20 = −3.9° (c = 2.5, CHCl3). Source: Sponges Dysidea amblia and Oceanapia bartschi. Pharm: Ichthyotoxin; algicide. Ref: R. P. Walker, et al, JOC, 1981, 46, 1098│F. Cafieri, et al, Z. Naturforsch., B, 1992, 48, 1408 OH

O

378 Ambliolide Type: 10,15-Cyclophytane diterpenoids. C21H34O4 Oil, [α]D20 = −4° (c = 2.2, CHCl3). Source: Sponge Dysidea amblia. Pharm: Ichthyotoxin Ref: R. P. Walker, et al, JOC, 1981, 46, 1098 OH O O

O

379 10,15-Cyclo-1,20-epoxy-1,3(20),6,11(18)-phytatetraene Dehydroambliol A Type: 10,15-Cyclophytane diterpenoids. C20H30O Oil, [α]D20 = −1.3° (c = 1.8, CHCl3). Source: Sponges Dysidea spp., Chelonaplysilla spp. and Dendrilla spp. Pharm: Ichthyotoxin. Ref: R. P. Walker, et al, JOC, 1981, 46, 1098│F. Cafieri, et al, Z. Naturforsch., B, 1992, 48, 1408

O

380 Irciniketene (4E,6E,8Z)-10,15-Cyclo-1,2,4,6,8,10-phytahexaen-1-one Type: 10,15-Cyclophytane diterpenoids. C20H26O Source: Sponge Ircinia selaginea (Guangxi Province, China). Pharm: Cytotoxic (moderate). Ref: S. Yan, et al, Gaodeng Xuexiao Huaxue Xuebao, 2001, 22, 949

3.2 10,15-Cyclophytane Diterpenoids

121

O

381 Laurencianol Type: 10,15-Cyclophytane diterpenoids. C20H35Br2ClO3 Crystal (C6H6/hexane), mp 114– 116 °C. Source: Red alga Laurencia obtusa. Pharm: Antibacterial. Ref: S. Caccamese, et al, Tet. Lett., 1982, 23, 3415 Cl

OH O

Br

OH

Br

382 Muquketone Type: 10,15-Cyclophytane diterpenoids. C18H30O Clear colorlessoil. Source: Sponge Diacarnus cf. spinopoculum (Solomon Is. and Papua New Guinea). Pharm: Differential cytotoxicity (softagar assay, 50 μg/disk, zone differential of 250 units is expected for “selectiveactivity”, M17 (mammary-17/Adr.)-L1210, -60 zone differential units); cytotoxic (HL60 (TB), GI50 = 2.88 μmol/L; Molt4, GI50 = 2.08 μmol/L; A549/ATCC, GI50 > 5.0 μmol/L; KM12, GI50 > 5.0 μmol/L; IGROV1, GI50 > 5.0 μmol/L; 786–0, GI50 > 5.0 μmol/L; BT549, GI50 > 5.0 μmol/L). Ref: S, Sperry, et al, JNP, 1998, 61, 241

O

383 Thuridillin B Type: 10,15-Cyclophytane diterpenoids. C24H32O8 [α]D25 = −9.4° (c = 0.48, CHCl3). Source: Sacoglossan Thuridilla hopei. Pharm: Defensive secretion. Ref: M. Gavagnin, et al, Gazz. Chim. Ital., 1993, 123, 205 O O O

O

O O

O

O

122

3 Diterpenoids

3.3 Linear Homo- and Nor- diterpenoids 384 Farnesylacetone epoxide Type: Linear homo- and nor-diterpenoids. C18H30O2 Oil, [α]D = −3.2° (c = 1, CHCl3). Source: Brown alga Cystophora moniliformis. Pharm: Anticonvulsant. Ref: R. Kazlauskas, et al, Experientia, 1978, 34, 156│B. N. Ravi, et al, Aust. J. Chem., 1982, 35, 171 O O

385 Hedaol A Type: Linear homo- and nor-diterpenoids. C18H30O2 Oil, [α]D29 = −1.9° (c = 0.057, CHCl3). Source: Brown alga Sargassum sp. (Japan waters). Pharm: Cytotoxic (P388, IC50 = 5.1 μg/mL). Ref: N. Takada, et al, JNP, 2001, 64, 653 5Z

O OH

386 Hedaol B Type: Linear homo- and nor-diterpenoids. C18H30O2 Oil, [α]D29 = −79° (c = 0.047, CHCl3). Source: Brown alga Sargassum sp. (Japan waters). Pharm: Cytotoxic (P388, IC50 = 2.2 μg/mL). Ref: N. Takada, et al, JNP, 2001, 64, 653 5

OH

O

387 Hedaol C Type: Linear homo- and nor-diterpenoids. C18H30O2 Oil, [α]D28 = −3° (c = 0.047, CHCl3). Source: Brown alga Sargassum sp. (Japan waters). Pharm: Cytotoxic (P388, IC50 = 50 μg/mL). Ref: N. Takada, et al, JNP, 2001, 64, 653 5E

O

OH

388 1-Nor-2,19-phytanediyl-di-O-sulfate Type: Linear homo- and nor-diterpenoids. C19H40O8S2 Amorph. solid, [α]D25 = +5° (c = 0.004, MeOH). Source: Ascidians Sidnyum turbinatum (Mediterranean Sea) and Ascidia mentula. Pharm: Antiproliferative (in vitro, WEHI-164, IC50 = (230 ± 5)μg/mL,

3.4 Labdane Diterpenoids

123

control 6-mercaptopurine, IC50 = (1.30 ± 0.02)μg/mL). Ref: A. Aiello, et al, JNP, 2001, 64, 219 OH O

S

O

O

O O

S

OH O

3.4 Labdane Diterpenoids 389 (–)-Cacofuran A Type: Labdane diterpenoids. C22H32O4 Glass, [α]D = −30° (c = 0.4, CH2Cl2). Source: Sponge Cacospongia sp. (Okinawa). Pharm: Cell growth/division Inhibitor (fertilised sea urchin eggs). Ref: J. Tanaka, et al, JNP, 2001, 64, 1468 O O O O

H

390 Cacofuran B Type: Labdane diterpenoids. C20H30O3 Cryst. (EtOAc/hexane), mp 141–145 °C, [α]D = −15° (c = 2, CH2Cl2). Source: Sponge Cacospongia sp. (Okinawa). Pharm: Cell growth/division Inhibitor (fertilised sea urchin eggs). Ref: J. Tanaka, et al, JNP, 2001, 64, 1468 O

HO O

H

391 Chlorolissoclimide Type: Labdane diterpenoids. C20H30ClNO4 Glass. Source: Ascidian Lissoclinum voeltzkowi. Pharm: Cytotoxic (high activity); toxic (Implicated in hmn food poisoning from

124

3 Diterpenoids

cooked oysters from whose shells had not been removed). Ref: J. -F. Biard, et al, Nat. Prod. Lett., 1994, 4, 43 OH H

O NH

Cl

O OH

H

392 Dichlorolissoclimide Type: Labdane diterpenoids. C20H29Cl2NO4 mp 210 °C, [α]D20 = +30° (c = 0.2, MeOH). Source: Ascidian Lissoclinum voeltzkowi. Pharm: Tyrosine metabolism and 5-aminolevulinic acid dehydrase inhibitor; toxic (Implicated in hmn food poisoning from cooked oysters from whose shells had not been removed). Ref: C. Malochet-Grivois, et al, Tet. Lett., 1991, 32, 6701│J. -F. Biard, et al, Nat. Prod. Lett., 1994, 4, 43 OH H

O NH

Cl O Cl

OH

H

393 ent-15,18-Dihydroxylabd-8(17),13E-diene Type: Labdane diterpenoids. C20H34O2 Source: Mangrove Excoecaria agallocha (stems and twigs, Guangxi province, China). Pharm: Anti-inflammatory (100 μmol/L, Inhibits pro-inflammatory cytokine TNFα released from Raw 264.7 cells, InRt = 13.2% (4h), 37.5% (16h); blocker of NF-κB activation. Ref: Y. Li, et al, Phytochemistry, 2010, 71, 2124│C. Zdero, et al, Phytochemistry, 1991, 30, 1591 HO

H

HO

H

394 Echinolabdane A Type: Labdane diterpenoids. C21H30O3 Yellowish oil, [α]D23 = +8° (c = 0.03, CHCl3). Source: Gorgonian Echinomuricea sp. (Taiwan Waters). Pharm: Antioxidant (superoxide anion O2∙– scavenger, IC50 > 10 μg/mL; 10 μg/mL, InRt = (2.52 ± 3.02)%, control DPI, IC50 = (0.82 ± 0.31)μg/mL); elastase release inhibitor (stimulated hmn

3.4 Labdane Diterpenoids

125

neutrophils, response to fMLP/CB, IC50 > 10 μg/mL, InRt = (1.83 ± 3.46)%, control Elastatinal, IC50 = (31.82 ± 5.92)μg/mL). Ref: H. -M. Chung, et al, Mar. Drugs, 2012, 10, 1169 O O O H H

395 Haterumaimide A Type: Labdane diterpenoids. C22H31Cl2NO5 [α]D29 = +31.3° (c = 0.13, MeOH). Source: Ascidian Lissoclinum sp. (Okinawa). Pharm: Cytotoxic. Ref: M. J. Uddin, et al, Heterocycles, 2001, 54, 1039 OH

H

O NH

Cl

O 7

Cl

O

O

H

396 Haterumaimide B Type: Labdane diterpenoids. C20H27Cl2NO4 [α]D33 = +32.6° (c = 0.48, MeOH). Source: Ascidian Lissoclinum sp. (Okinawa). Pharm: Cytotoxic. Ref: M. J. Uddin, et al, Heterocycles, 2001, 54, 1039 O

H N O

H OH Cl 6

Cl

H

O

397 Haterumaimide C Type: Labdane diterpenoids. C20H27Cl2NO4 [α]D28 = +66.6° (c = 0.06, MeOH). Source: Ascidian Lissoclinum sp. (Okinawa). Pharm: Cytotoxic. Ref: M. J. Uddin, et al, Heterocycles, 2001, 54, 1039

126

3 Diterpenoids

O

H N O

H H H O

Cl Cl

H

O

398 Haterumaimide D Type: Labdane diterpenoids. C20H27Cl2NO4 [α]D29 = −27.7° (c = 0.16, MeOH). Source: Ascidian Lissoclinum sp. (Okinawa). Pharm: Cytotoxic. Ref: M. J. Uddin, et al, Heterocycles, 2001, 54, 1039 O

H N O

H OH Cl 6

Cl

H

O

399 Haterumaimide E Type: Labdane diterpenoids. C20H29Cl2NO4 [α]D29 = +29.6° (c = 0.16, MeOH). Source: Ascidian Lissoclinum sp. (Okinawa). Pharm: Cytotoxic. Ref: M. J. Uddin, et al, Heterocycles, 2001, 54, 1039 O

H

H N O OH

Cl Cl

H

OH

400 Haterumaimide F Type: Labdane diterpenoids. C20H30ClNO4 Oil, [α]D29 = +53.7° (c = 0.35, MeOH). Source: Ascidian Lissoclinum sp. (Okinawa). Pharm: Inhibits first cleavage of

3.4 Labdane Diterpenoids

127

fertilized sea urchin eggs; cytotoxic (P388, IC50 = 0.0055 μg/mL). Ref: M. J. Uddin, et al, JNP, 2001, 64, 1169 O

H N O

H OH Cl H H

OH

401 Haterumaimide G Type: Labdane diterpenoids. C20H28ClNO4 Oil, [α]D29 = +63.5° (c = 0.58, MeOH). Source: Ascidian Lissoclinum sp. (Okinawa). Pharm: Inhibits first cleavage of fertilized sea urchin eggs; cytotoxic (P388, IC50 > 10 μg/mL). Ref: M. J. Uddin, et al, JNP, 2001, 64, 1169 O

H N O

H OH Cl H H

O

402 Haterumaimide H Type: Labdane diterpenoids. C20H28ClNO4 Oil, [α]D32 = +47.6° (c = 0.31, MeOH). Source: Ascidian Lissoclinum sp. (Okinawa). Pharm: Inhibits first cleavage of fertilized sea urchin eggs; cytotoxic (P388, IC50 = 2.7 μg/mL). Ref: M. J. Uddin, et al, JNP, 2001, 64, 1169 O

H N O

H OH Cl H H

O

128

3 Diterpenoids

403 Haterumaimide I Type: Labdane diterpenoids. C20H28ClNO4 Oil, [α]D32 = +62° (c = 0.77, MeOH). Source: Ascidian Lissoclinum sp. (Okinawa). Pharm: Inhibits first cleavage of fertilized sea urchin eggs; cytotoxic (P388, IC50 > 10 μg/mL). Ref: M. J. Uddin, et al, JNP, 2001, 64, 1169 O

H N O

H H O

Cl H H

O

404 Labdane aldehyde TL95-8673A Type: Labdane diterpenoids. C20H34O2 [α]D25 = −35.2° (c = 0.3, CHCl3). Source: Notapsid Pleurobranchaea meckelii (Mediterranean Sea). Pharm: Protectant of mollusc. Ref: M. L. Ciavatta, et al, Tet. Lett., 1995, 36, 8673

O OH

405 Labdane aldehyde TL95-8673B Type: Labdane diterpenoids. C20H34O2 [α]D25 = −28.2° (c = 0.27, CHCl3). Source: Notapsid Pleurobranchaea meckelii (Mediterranean Sea). Pharm: Protectant of mollusc. Ref: M. L. Ciavatta, et al, Tet. Lett., 1995, 36, 8673 O

OH

3.5 Halimane Diterpenoids

129

406 Verrucosin 5 Type: Labdane diterpenoids. C25H40O5 Oil, [α]D = −15.9° (c = 0.27, CHCl3). Source: Nudibranch Doris verrucosa (Mediterranean Sea). Pharm: PKC activator. Ref: M. Gavagnin, et al, Tetrahedron, 1997, 53, 1491 OH O

O

O

O

407 Sphaerolabdiene-3,14-diol Type: Seco-labdane diterpenoids. C20H33BrO2 Amorph. powder, [α]D = +9.6° (c = 0.6, CH2Cl2). Source: Red alga Sphaerococcus coronopifolius (Atlantic coast of Morocco). Pharm: Antibacterial (Staphylococcus aureus, high active). Ref: S. Etahiri, et al, JNP, 2001, 64, 1024

OH Br

OH

3.5 Halimane Diterpenoids 408 Agelasine C Type: Halimane diterpenoids C26H40N51+ mp 176–179 °C (chloride), [α]D25 = −55.1° (c = 2.04, MeOH) (chloride). Source: Sponges Agelas nakamurai (Okinawa) and Agelas sp. (Pacific Ocean). Pharm: Antimicrobial; ATP-ase inhibitor; spasmolytic. Ref: I. Marcos, et al, Tetrahedron, 2005, 61, 11672│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev) N N+

N N NH2

H

130

3 Diterpenoids

409 5,9-diepi-Agelasine C Type: Halimane diterpenoids C26H40N51+ Powder (chloride), [α]D25 = +33.9° (c = 0.056, MeOH) (chloride). Source: Sponge Agelas mauritiana. Pharm: Antifoulant (Ulva sp. spores, not as high as that of control CuSO4, lethal activity against Ulva fronds at 50 ppm); antimicroalgal (Oscillatoria amphibian (Cyanophyceae), Skeletonema costatum (Diatomophyceae), Brachiomonas submaria (Chlorophyceae) and Prorocentrum micans (Dinophyceae), 1.0–2.5 ppm, so it seems to be useful as a measure to counter red tide). Ref: T. Hattori, et al, JNP, 1997, 60, 411│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev) NH2 N+ 9

10

N

8

N

N

H 18

410 Agelasine J Type: Halimane diterpenoids C26H40N51+ Powder, [α]D25 = +14° (c = 0.46, MeOH). Source: Sponge Agelas cf. mauritiana (Solomon Is.). Pharm: Antimalarial (Plasmodium falciparum, IC50 = 6.6 μmol/L). Ref: J. Appenzeller, et al, JNP, 2008, 71, 1451│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev) NH2 N 9

10

+

N

8

N

N

18

411 Agelasine O Type: Halimane diterpenoids C31H42BrN6O21+ Pale yellow amorphous solid, [α]D19 = −5.2° (c = 0.5, MeOH). Source: Sponge Agelas sp. (Okinawa). Pharm: Antibacterial (Escherichia coli, MIC > 32.0 μg/mL, Staphylococcus aureus, MIC = 16.0 μg/mL, Bacillus subtilis, MIC = 16.0 μg/mL, Micrococcus luteus, MIC > 32.0 μg/mL); antifungal (Aspergillus niger, IC50 > 32.0 μg/mL, Trichophyton mentagrophytes, IC50 = 32.0 μg/mL, Candida albicans, IC50 > 32.0 μg/mL, Cryptococcus neoformans, IC50 = 16.0 μg/mL). Ref: T. Kubota, et al, Tetrahedron, 2012, 68, 9738 NH2

Br N

N

HN N O

O

+

N

3.5 Halimane Diterpenoids

131

412 Agelasine S Type: Halimane diterpenoids C26H40N5O21+ Colorless amorphous solid, [α]D20 = −5.4° (c = 0.5, MeOH). Source: Sponge Agelas sp. (Okinawa). Pharm: Antibacterial (Escherichia coli, MIC > 32.0 μg/mL, Staphylococcus aureus, MIC > 32.0 μg/mL, Bacillus subtilis, MIC > 32.0 μg/mL, Micrococcus luteus, MIC > 32.0 μg/mL); antifungal (Aspergillus niger, IC50 > 32.0 μg/mL, Trichophyton mentagrophytes, IC50 > 32.0 μg/mL, Candida albicans, IC50 > 32.0 μg/mL, Cryptococcus neoformans, IC50 > 32.0 μg/mL). Ref: T. Kubota, et al, Tetrahedron, 2012, 68, 9738 NH2

OH N N

HO

N +

N

413 (+)-Agelisamine A Type: Halimane diterpenoids C27H43N5O Yellowish oil, [α]D25 = +2.3° (MeOH). Source: Sponge Agelas mauritiana. Pharm: Cell growth inhibitor; inhibits nucleoside transport into erythrocytes (rbt); Ca2+-channel antagonistic action and α1 adrenergic blocker. Ref: R. Fathi-Afshar, et al, Can. J. Chem., 1988, 66, 45│M. Ohba, et al, Tet. Lett., 1995, 36, 6101│M.Ohba,et al, Tetrahedron, 1997, 53, 16977 N

N N

H

N

N

OH

414 (+)-Agelisamine B Type: Halimane diterpenoids C27H45N5O Viscous yellowish oil, [α]D25 = +2.46° (MeOH). Source: Sponge Agelas mauritiana (Solomon Is.). Pharm: Cytotoxic; inhibition of adenosine transfer into rabbit erythrocytes; Ca2+-channel antagonistic action and α1 adrenergic blockade. Ref: R. Fathi-Afshar, et al, Can. J. Chem., 1988, 66, 45│M. Ohba, et al, Tet. Lett., 1995, 36, 6101│M.Ohba, et al, Tetrahedron, 1997, 53, 16977 N

N N

H

OH

HN

N

132

3 Diterpenoids

415 Ambliol B (5β,8αH)-15,16-Epoxy-13(16),14-halimadien-5-ol Type: Halimane diterpenoids C20H32O2 Oil, [α]D20 = −3.4° (c = 1.5, CHCl3). Source: Sponge Dysidea amblia. Pharm: Ichthyotoxin; algicide. Ref: R. P. Walker, et al, JOC, 1981, 46, 1098; 1984, 49, 5160 O

H 8 5

OH

416 Ambliol C Type: Halimane diterpenoids C20H32O2 Cryst. (hexane), mp 45–46 °C, [α]D = −37.8° (c = 2, CHCl3). Source: Sponge Dysidea amblia (Pt. Loma, California). Pharm: Ichthyotoxin; algicide. Ref: R. P. Walker, et al, JOC, 1981, 46, 1098; 1984, 49, 5160 O

H 8 5

OH

417 Austrodorin Type: Halimane diterpenoids C23H40O4 Source: Nudibranch Austrodoris kerguelenensis. Pharm: Cytotoxic (echinoderms); noxious to Antarctic fish. Ref: M. Gavagnin, et al, Tet. Lett., 1995, 36, 7319 OH O

OH

O H

418 7-[5-(Decahydro-4a-hydroxy-1,2,5,5-tetramethyl-1-naphthalenyl)3-methyl-2-pentenyl]-3,7-dihydro-2,3-dimethyl-6H-purin-6-one Type: Halimane diterpenoids C27H42N4O2 Cryst. (C6H6) (Ac), mp 95–98 °C (Ac). Source: Sponge Agelas mauritiana. Pharm: Antimicrobial. Ref: T. Nakatsu, et al, Tet. Lett., 1984, 25, 935

3.6 Clerodane Diterpenoids

N

H

O

133

N N

N

OH

419 Echinohalimane A Type: Halimane diterpenoids C20H30O3 Yellowish oil, [α]D25 = −102° (c = 1.69, CHCl3). Source: Gorgonian Echinomuricea sp. (Taiwan Waters). Pharm: Cytotoxic (K562, IC50 = 6.292 μg/mL, control Doxorubicin, IC50 = 0.171 μg/mL; Molt4, IC50 = 2.111 μg/mL, Doxorubicin, IC50 = 0.001 μg/mL; HL60, IC50 = 2.117 μg/mL, Doxorubicin, IC50 = 0.048 μg/mL; DLD-1, IC50 = 0.967 μg/mL, Doxorubicin, IC50 = 2.322 μg/mL; LoVo, IC50 = 0.563 μg/mL, Doxorubicin, IC50 = 0.959 μg/mL; DU145, 20 μg/mL inactive, Doxorubicin IC50 = 0.005 μg/mL); antioxidant (superoxide anion ∙O2– scavenger, IC50 > 10 μg/mL; 10 μg/mL, InRt = (20.55 ± 5.18)%, control DPI, IC50 = (0.80 ± 0.21)μg/mL); elastase release inhibitor (stimulated hmn neutrophils, response to fMLP/CB, IC50 = (0.38 ± 0.14)μg/mL, control Elastatinal, IC50 = (31.95 ± 5.92)μg/mL). Ref: H. -M. Chung, et al, Mar. Drugs, 2012, 10, 2246 OH O O H

3.6 Clerodane Diterpenoids 420 Agelasine A Type: Clerodane diterpenoids. C26H40N51+ Cryst. (as chloride), mp 173–174 °c (chloride), [α]D25 = −31.3° (c = 0.59, MeOH). Source: Sponges Agelas nakamurai (Okinawa) and Agelas sp. (Pacific Ocean). Pharm: Antifungal (Aspergillus niger, 10 μg/mL; Saccharomyces cerevisiae 1 μg/mL); Na+/K+-transporting ATPase inhibitor (in vitro); smooth muscle contractant. Ref: H. Wu, et al, Bull. Chem. Soc. Jpn., 1986, 59, 2495│E. Piers, et al, JCS Perkin I, 1995, 963│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev)

134

3 Diterpenoids

NH2

H 10

N 9

+

N

8

N

N

18

421 Agelasine B Type: Clerodane diterpenoids. C26H40N51+ Cryst. (chloride), mp 167–170 °C (chloride), [α]D25 = −21.5° (c = 1.00, MeOH). Source: Sponges Agelas nakamurai (Okinawa) and Agelas sp.(Pacific Ocean). Pharm: Antifungal (Saccharomyces cerevisiae,10 μg/mL); NaKATPase inhibitor (10−4 mol/L); spasmolytic. Ref: H. Nakamura, et al, Tet. Lett., 1984, 25, 2989│H. Wu, et al, Bull. Chem. Soc. Jpn., 1986, 59, 2495│E. Piers, et al, Tet. Lett., 1992, 33, 6923│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev) N N+ H

N N NH2

422 Agelasine D Type: Clerodane diterpenoids. C26H40N51+ mp 175–176 °C (chloride), [α]D25 = +10.4° (c = 1.1, MeOH) (chloride). Source: Sponges Agelas nakamurai (Okinawa), Agelas sp. (Pacific Ocean) and Agelas sp. (Indonesia). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 = 0.63 μmol/L; selective SI: (IC50(MCR-5 fibroblast)/IC50 (Plasmodium falciparum)) = 23); antimalarial (selectivity index SI: (IC50 (MCR-5 fibroblast)/IC50 (Plasmodium falciparum)) = 23); spasmolytic; antibacterial (broad spectrum including Mycobacterium tuberculosis, gram-positive and gram-negative bacteria both aerobes and anaerobes); antibacterial (Staphylococcus epidermis, MIC = 0.09 μmol/L); Na/ K-ATPase inhibitor; antifoulant (strongly inhibits settlement of cypris larvae of barnacle Balanus amphitrite, EC50 = 0.11–0.30 μmol/L, inactive to larval mortality). Ref: H. Nakamura, et al, Tetra. Lett., 1984, 25, 2989│H. Wu, et al, Bull. Chem. Soc. Jpn., 1986, 59, 2495│A. Vik, et al, JNP, 2006, 69, 381│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev)│T. Hertiani, et al, BoMC 2010, 18, 1297

3.6 Clerodane Diterpenoids

135

NH2 9

10

N

+

N

8

N

N

423 Agelasine G Type: Clerodane diterpenoids. C31H42BrN6O21+ [α]D27 = −85° (c = 0.02, CHCl3). Source: Sponge Agelas sp. (Okinawa). Pharm: Cytotoxic (in vitro murine lymphoma L1210 cells, IC50 = 3.1 μg/mL). Ref: K. Ishida, et al, CPB, 1992, 40, 766│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev) NH2

H 9

10

N+

N

8

N 18

O

N

H N

O

Br

424 Agelasine H Type: Clerodane diterpenoids. C26H40N5O1+ Amorph. solid (chloride), [α]D = −63.9° (c = 0.36, MeOH). Source: Sponge Agelas mauritiana (Yap Island, Federated States of Micronesia). Pharm: Antifungal (Aspergillus niger, 10 μg/mL; Saccharomyces cerevisiae 1 μg/mL). Ref: X. Fu, et al, JNP, 1998, 61, 548│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev) NH2

H

N 9

10

+

N 18

N

8

N

OH

425 Agelasine I Type: Clerodane diterpenoids. C26H40N5O1+ Amorph. solid (chloride), [α]D = −2.5° (c = 0.20, MeOH). Source: Sponge Agelas mauritiana (Yap Island, Federated States of Micronesia). Pharm: Antifungal (Saccharomyces cerevisiae, 200 μg/mL). Ref: X. Fu, et al, JNP, 1998, 61, 548│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev)

136

3 Diterpenoids

NH2

H 9

10

N

+

N

8

N

HO

N

426 Agelasine K Type: Clerodane diterpenoids. C26H40N51+ Powder, [α]D25 = +60° (c = 0.11, MeOH). Source: Sponge Agelas cf. mauritiana (Solomon Is.). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 = 8.3 μmol/L). Ref: J. Appenzeller, et al, JNP, 2008, 71, 1451│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev) NH2

H 10

N+ 9

N

8

N

N

18

427 Agelasine L Type: Clerodane diterpenoids. C26H40N51+ Powder, [α]D25 = −3.2° (c = 1, MeOH). Source: Sponge Agelas cf. mauritiana (Solomon Is.). Pharm: Antimalarial (Plasmodium falciparum, IC50 = 18 μmol/L). Ref: J. Appenzeller, et al, JNP, 2008, 71, 1451│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev) NH2 N 10

9

+

N

8

N

N

18

428 Agelasine P Type: Clerodane diterpenoids. C31H40BrN6O31+ Pale yellow amorphous solid, [α]D20 = +4.5° (c = 0.5, MeOH). Source: Sponge Agelas sp. (Okinawa). Pharm: Antibacterial (Escherichia coli, MIC > 32.0 μg/mL, Staphylococcus aureus, MIC = 32.0 μg/mL, Bacillus subtilis, MIC = 32.0 μg/mL, Micrococcus luteus, MIC > 32.0 μg/mL); antifungal (Aspergillus niger, IC50 > 32.0 μg/mL, Trichophyton mentagrophytes, IC50 > 32.0 μg/mL, Candida albicans, IC50 > 32.0 μg/mL, Cryptococcus neoformans, IC50 = 32.0 μg/mL). Ref: T. Kubota, et al, Tetrahedron, 2012, 68, 9738

3.6 Clerodane Diterpenoids

Br

NH2

H

O

N N

N H O

137

N +

N

O

429 Agelasine Q Type: Clerodane diterpenoids. C31H40BrN6O31+ Pale yellow amorphous solid, [α]D20 = +6.8° (c = 0.39, MeOH). Source: Sponge Agelas sp. (Okinawa). Pharm: Antibacterial (Escherichia coli, MIC > 32.0 μg/mL, Staphylococcus aureus, MIC = 8.0 μg/mL, Bacillus subtilis, MIC = 8.0 μg/mL, Micrococcus luteus, MIC > 32.0 μg/mL); Antifungal (Aspergillus niger, IC50 = 16.0 μg/mL, Trichophyton mentagrophytes, IC50 = 16.0 μg/mL, Candida albicans, IC50 = 16.0 μg/mL, Cryptococcus neoformans, IC50 = 8.0 μg/mL). Ref: T. Kubota, et al, Tetrahedron, 2012, 68, 9738 Br

H

O

NH2 N N

N H O

N +

N

O

430 Agelasine R Type: Clerodane diterpenoids. C31H40BrN6O31+ Pale yellow amorphous solid, [α]D22 = −13.0° (c = 0.29, MeOH). Source: Sponge Agelas sp. (Okinawa). Pharm: Antibacterial (Escherichia coli, MIC > 32.0 μg/mL, Staphylococcus aureus, MIC = 8.0 μg/mL, Bacillus subtilis, MIC = 8.0 μg/mL, Micrococcus luteus, MIC > 32.0 μg/mL); antifungal (Aspergillus niger, IC50 = 16.0 μg/mL, Trichophyton mentagrophytes, IC50 = 16.0 μg/mL, Candida albicans, IC50 = 16.0 μg/mL, Cryptococcus neoformans, IC50 = 8.0 μg/mL). Ref: T. Kubota, et al, Tetrahedron, 2012, 68, 9738 Br

N H O

H

O

NH2 N N

N +

N

O

431 Agelasine T Type: Clerodane diterpenoids. C26H42N5O1+ Colorless amorphous solid, [α]D20 = −0.9° (c = 0.5, MeOH). Source: Sponge Agelas sp. (Okinawa). Pharm: Antibacterial

138

3 Diterpenoids

(Escherichia coli, MIC > 32.0 μg/mL, Staphylococcus aureus, MIC = 16.0 μg/mL, Bacillus subtilis, MIC = 16.0 μg/mL, Micrococcus luteus, MIC > 32.0 μg/mL); antifungal (Aspergillus niger, IC50 > 32.0 μg/mL, Trichophyton mentagrophytes, IC50 > 32.0 μg/mL, Candida albicans, IC50 > 32.0 μg/mL, Cryptococcus neoformans, IC50 = 16.0 μg/mL). Ref: T. Kubota, et al, Tetrahedron, 2012, 68, 9738 NH2

H

N OH

N

N +

N

H

432 Agelasine U Type: Clerodane diterpenoids. C26H40N5O1+ Pale yellow amorphous solid, [α]D23 = −4.1° (c = 0.29, MeOH). Source: Sponge Agelas sp. (Okinawa). Pharm: Antibacterial (Escherichia coli, MIC > 32.0 μg/mL, Staphylococcus aureus, MIC > 32.0 μg/mL, Bacillus subtilis, MIC > 32.0 μg/mL, Micrococcus luteus, MIC > 32.0 μg/mL); antifungal (Aspergillus niger, IC50 > 32.0 μg/mL, Trichophyton mentagrophytes, IC50 > 32.0 μg/mL, Candida albicans, IC50 > 32.0 μg/mL, Cryptococcus neoformans, IC50 > 32.0 μg/mL). Ref: T. Kubota, et al, Tetrahedron, 2012, 68, 9738 NH2

H

N N

HO

N +

N

433 Ageline B Type: Clerodane diterpenoids. C31H43N6O21+ Source: Sponges Agelas nakamurai (Okinawa), Agelas sp. (Pacific Ocean) and Agelas sp. (Palau, Western Caroline I., Pacific). Pharm: Antibacterial (gram-positive bacteria Staphylococcus aureus); antifungal (Saccharomyces cerevisiae, 10 μg/mL; Candida albicans; Candida utilis); ATPase inhibitor; smooth muscle contractor; phytotoxin; ichthyotoxin (weak). Ref: R. J. Capon, et al, JACS, 1984, 106, 1819│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev) NH2

H 9

10

N

+

N 18

O

O

N

8

H N

N

3.6 Clerodane Diterpenoids

139

434 Asmarine A Type: Clerodane diterpenoids. C25H37N5O Cryst. (MeOH), mp 232 °C, [α]D = +55° (c = 0.5, CHCl3). Source: Sponges Raspailia spp. (near Nakora I., Dahlak Archipielago, Eritrea, Red Sea; Nosy Be Is., Madagascar). Pharm: Cytotoxic (P388, IC50 = 1.18 μmol/ L, A549, IC50 = 1.18 μmol/L, HT29, IC50 = 1.18 μmol/L, MEL28, IC50 = 1.18 μmol/L). Ref: T. Yosief, et al, Tetra. Lett., 1998, 39, 3323│T. Yosief, et al, JNP, 2000, 63, 299│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev) N

N 13

N OH

H

N N

5

435 Asmarine B Type: Clerodane diterpenoids. C25H37N5O Oil, [α]D = +60° (c = 0.5, CHCl3). Source: Sponge Raspailia sp. (near Nakora I., Dahlak Archipielago, Eritrea, Red Sea). Pharm: Cytotoxic (P388, IC50 = 0.24 μmol/L, A549, IC50 = 0.24 μmol/L, HT29, IC50 = 0.24 μmol/L, MEL28, IC50 = 0.24 μmol/L); cytotoxic (P388, HT29, MEL28, IC50 = 0.12–0.24 μmol/L); cytotoxic (DU145, IGROV-ET, A549 NSCL, PANC1, LoVo, GI50 = 0.04–0.5 μg/mL). Ref: T. Yosief, et al, Tetra. Lett., 1998, 39, 3323│T. Yosief, et al, JNP, 2000, 63, 299│M. Gordaliza, Mar. Drugs, 2009, 7, 833 (rev) 8' N

N 13 N

N N

OH H

5

436 Echinoclerodane A Type: Clerodane diterpenoids. C21H30O3 Source: Gorgonian Echinomuricea sp. (Taiwan Waters). Pharm: Cytotoxic (K562, IC50 = 37.05 μmol/L, control Doxorubicin, IC50 = 0.29 μmol/L; Molt4, IC50 = 13.18 μmol/L, Doxorubicin, IC50 = 0.001 μmol/L; HL60, IC50 = 14.89 μmol/L, Doxorubicin, IC50 = 0.08 μmol/L; DLD-1, IC50 = 23.44 μmol/L, Doxorubicin, IC50 = 4.00 μmol/L; LoVo, IC50 = 21.69 μmol/L, Doxorubicin, IC50 = 1.65 μmol/L; DU145, IC50 = 53.93 μmol/L, Doxorubicin IC50 = 0.01 μmol/L); antioxidant (superoxide anion ∙O2– scavenger, InRt = 68.6%); elastase release

140

3 Diterpenoids

inhibitor (stimulated hmn neutrophils, 10 μg/mL, InRt = 35.4%). Ref: C. -H. Cheng, et al, Molecules, 2012, 17, 9443 OH H

O O

437 Palmadorin A Type: Clerodane diterpenoids. C23H38O4 Colorless oil, [α]D25 = +18° (c = 0.05, MeOH). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64° 03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, IC50 = (8.7 ±0.4)μmol/L). Ref: T. Diyabalanage, et al, JNP, 2010, 73, 416│J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 H

O O

4

OH

18

OH

438 Palmadorin B Type: Clerodane diterpenoids. C23H40O5 Colorless oil, [α]D25 = +24° (c = 0.05, MeOH). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64° 03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, IC50 = (8.3 ± 0.8)μmol/L). Ref: T. Diyabalanage, et al, JNP, 2010, 73, 416│J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 H 4

18

O O

O O OH

439 Palmadorin C Type: Clerodane diterpenoids. C23H38O5 Colorless oil, [α]D25 = +8° (c = 0.05, MeOH). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: T. Diyabalanage, et al, JNP, 2010, 73, 416│J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095

3.6 Clerodane Diterpenoids

OH

O H

141

OH

O

4

OH 18

440 Palmadorin D Type: Clerodane diterpenoids. C23H38O4 Colorless oil, [α]D20 = +15° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, depth of 1–40 m, along Anvers Island close to Palmer Station, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, IC50 = (16.5 ± 0.1) μmol/L). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O 20

H

17

O

4

18

OH OH

19

441 Palmadorin E Type: Clerodane diterpenoids. C23H36O6 Colorless oil, [α]D20 = +6° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O H

O

20 17

4

OH 18

O

OH OH

19

442 Palmadorin F Type: Clerodane diterpenoids. C23H38O5 Colorless oil, [α]D20 = +41° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095

142

3 Diterpenoids

O 20

H

17

O

4

OH 18

OH OH

19

443 Palmadorin G Type: Clerodane diterpenoids. C23H36O5 Colorless oil, [α]D20 = +13° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O 20

H

O

17

O

4

18

OH OH

19

444 Palmadorin H Type: Clerodane diterpenoids. C25H40O6 Colorless oil, [α]D20 = +16° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O O H

O

20 17

O

OH

4

OH 18

19

445 Palmadorin I Type: Clerodane diterpenoids. C23H34O6 Colorless oil, [α]D20 = +11° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095

3.6 Clerodane Diterpenoids

143

O H

O

20 17

O

OH

4

OH

O 18

19

446 Palmadorin J Type: Clerodane diterpenoids. C23H36O6 Colorless oil, [α]D20 = +8° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O H

O

OH

20

O

17

OH

4

OH 18

19

447 Palmadorin K Type: Clerodane diterpenoids. C23H34O6 Colorless oil. Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O H

O

OH

20

O

17

OH

4

O 18

19

448 Palmadorin L Type: Clerodane diterpenoids. C23H39ClO5 Colorless oil, [α]D20 = +25° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O H

20 17

4

HO 18

O

OH OH

19

Cl

144

3 Diterpenoids

449 Palmadorin M Type: Clerodane diterpenoids. C23H38O4 Colorless oil, [α]D20 = −18° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, IC50 = (4.9 ± 0.4)μmol/L); inhibits Jak2, STAT5, and Erk1/2 activation (in hmn erythroleukemia cells and causes apoptosis, 5 μmol/L). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O

OH

20

O

OH

4

H 18

19

450 Palmadorin N Type: Clerodane diterpenoids. C23H38O4 Colorless oil, [α]D20 = −10° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, IC50 = (6.3 ± 0.5)μmol/L). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O 20

O

OH OH

4

H 18

19

451 Palmadorin O Type: Clerodane diterpenoids. C25H40O5 Colorless oil, [α]D20 = −10° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, IC50 = (13.4 ± 0.4)μmol/L). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O O

O

20

O 4

H 18

19

OH

3.6 Clerodane Diterpenoids

145

452 Palmadorin P Type: Clerodane diterpenoids. C23H40O5 Colorless oil, [α]D20 = −9° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O 20

OH

O

OH OH

4

H 18

19

453 Palmadorin Q Type: Clerodane diterpenoids. C23H40O5 Colorless oil, [α]D20 = −3° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O 20

OH

O

OH OH

4

H 18

19

454 Palmadorin R Type: Clerodane diterpenoids. C25H40O6 Colorless oil, [α]D20 = +53° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O 20

O

17

O

H 18

19

OH O

4

O

146

3 Diterpenoids

455 Palmadorin S Type: Clerodane diterpenoids. C23H38O5 Colorless oil, [α]D20 = +29° (c = 0.1, CHCl3). Source: Nudibranch Austrodoris kerguelenensis (Antarctic, 64°46.5’S, 64°03.3ʹW). Pharm: Cytotoxic (Jak2/STAT5-dependent hmn erythroleukemia cells, 10 μmol/L for 5days, viable cell = 50–80%, weak). Ref: J. A. Maschek, et al, Tetrahedron, 2012, 68, 9095 O 20

O

17

O

OH OH

4

H 18

19

456 Popolohuanone F Type: Clerodane diterpenoids. C42H57NO3 Amorph. violet solid. Source: Sponge Dysidea sp. Pharm: Antioxidant (DPPH scavenger, IC50 = 35 μmol/L). Ref: N. K. Utkina, et al, JNP, 2010, 73, 788│M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev) O

NH

H

O

H

OH

457 ent-14,15-Dinor-4(18)-cleroden-13-one Type: Clerodane diterpenoids. C18H30O Oil, [α]D = +43° (c = 1.2, CHCl3). Source: Sponges Diacarnus cf. spinopoculum (Solomon Is. and Papua New Guinea) and Mycale sp. (southern Australia). Pharm: Differential cytotoxicity (softagar assay, 50 μg/disk, zone differential of 250 units is expected for “selectiveactivity”, M17-L1210, 0 zone differential units). Ref: R. J. Capon, et al, JNP, 1997, 60, 1261│S. Sperry, et al, JNP, 1998, 61, 241 O H

3.7 Isopimarane Diterpenoids

147

3.7 Isopimarane Diterpenoids 458 11-Deoxydiaporthein A Type: Isopimarane diterpenoids. C20H30O5 Cryst. [α]D25 = +61.1° (c = 0.46, CHCl3). Source: Marine-derived fungi Eutypella scoparia (sediment, South China Sea), and Cryptosphaeria eunomia var. eunomia. Pharm: Cytotoxic (SF268, IC50 > 100 μmol/L, control Cisplatin, IC50 = 4.0 μmol/L; MCF7, IC50 > 100 μmol/L, Cisplatin, IC50 = 9.2 μmol/L; NCI-H460, IC50 > 100 μmol/L, Cisplatin, IC50 = 1.5 μmol/L). Ref: S. Yoshida, et al, Chem. Lett., 2007, 36, 1386│L. Sun, Chin. Tradit. Herb. Drugs 2011, 42, 432│L. Sun, et al, Mar. Drugs, 2012, 10, 539

OH OH

O

H

OH OH

459 Diaporthein A Type: Isopimarane diterpenoids. C20H30O6 Solid, mp 198–200 °C, [α]D31 = +25.8° (c = 0.124, CHCl3). Source: Marine-derived fungus Eutypella scoparia (sediment, South China Sea). Pharm: Antimycobacterial; cytotoxic (SF268, IC50 > 100 μmol/L, control Cisplatin, IC50 = 4.0 μmol/L; MCF7, IC50 > 100 μmol/L, Cisplatin, IC50 = 9.2 μmol/L; NCI-H460, IC50 > 100 μmol/L, Cisplatin, IC50 = 1.5 μmol/L). Ref: L. Sun, Chin. Tradit. Herb. Drugs 2011, 42, 432│L. Sun, et al, Mar. Drugs, 2012, 10, 539 HO OH O OH OH

OH H

460 Diaporthein B Type: Isopimarane diterpenoids. C20H28O6 Solid, mp 219–220 °C, [α]D31 = +120.1° (c = 0.106, CHCl3). Source: Marine-derived fungus Eutypella scoparia (sediment, South China Sea). Pharm: Antimycobacterial; cytotoxic (SF268, IC50 = 9.2 μmol/L, control Cisplatin, IC50 = 4.0 μmol/L; MCF7, IC50 = 4.4 μmol/L, Cisplatin, IC50 = 9.2 μmol/L; NCI-H460, IC50 = 9.9 μmol/L, Cisplatin, IC50 = 1.5 μmol/L). Ref: L. Sun, Chin. Tradit. Herb. Drugs 2011, 42, 432│L. Sun, et al, Mar. Drugs, 2012, 10, 539

148

3 Diterpenoids

HO OH O OH

O OH

461 Gifhornenolone A Type: Isopimarane diterpenoids. C19H28O2 Colorless needles, mp 94–95 °C (crystallized from AcOEt—n-Hexane), [α]D25 = +6.61° (c = 0.18, CHCl3). Source: Marine-derived bacterium Verrucosispora gifhornensis from unidentified ascidian (Hiroshima, Japan). Pharm: Androgen antagonist (inhibitor of binding of dihydroxytestosterone (DHT) to androgen receptor, IC50 = 2.8 μg/mL (9.7 μmol/L)). Ref: M. Shirai, et al, J. Antibiot., 2010, 63, 245

O H H HO

462 Isopimara-8(14),15-diene Type: Isopimarane diterpenoids. C20H32 Source: Marine-derived fungus Eutypella scoparia (sediment, South China Sea). Pharm: Cytotoxic (SF268, IC50 > 100 μmol/L, control Cisplatin, IC50 = 4.0 μmol/L; MCF7, IC50 > 100 μmol/L, Cisplatin, IC50 = 9.2 μmol/L; NCI-H460, IC50 > 100 μmol/L, Cisplatin, IC50 = 1.5 μmol/L). Ref: L. Sun, Chin. Tradit. Herb. Drugs 2011, 42, 432│L. Sun, et al, Mar. Drugs, 2012, 10, 539

463 Libertellenone A Type: Isopimarane diterpenoids. C20H28O4 Colorless crystals or powder, [α]D = −96.8° (c = 0.133, MeCN). Source: Marine-derived fungi Eutypella scoparia (sediment, South China Sea) and Libertella sp. Pharm: Cytotoxic (SF268, IC50 = 20.5 μmol/L, control Cisplatin, IC50 = 4.0 μmol/L; MCF7, IC50 = 12.0 μmol/L, Cisplatin, IC50 = 9.2 μmol/L; NCI-H460, IC50 = 40.2 μmol/L, Cisplatin, IC50 = 1.5 μmol/L). Ref:

3.7 Isopimarane Diterpenoids

149

D. -C. Oh, et al, BoMC, 2005, 13, 5267│L. Sun, Chin. Tradit. Herb. Drugs 2011, 42, 432│L. Sun, et al, Mar. Drugs, 2012, 10, 539 OH

OH O OH

464 Libertellenone C Type: Isopimarane diterpenoids. C20H28O5 Powder, [α]D = −84.1° (c = 0.387, MeCN). Source: Marine-derived fungus Arthrinium sacchari from unidentified sponge (Atamishi, Shizuoka, Japan), marine-derived Libertella sp. Pharm: Antiangiogenic. Ref: D. -C. Oh, et al, BoMC, 2005, 13, 5267│M. Tsukada, et al, JNP, 2011, 74, 1645 OH

OH O HO

OH

465 Libertellenone G Type: Isopimarane diterpenoids. C20H66O3 Source: Marine fungus Eutypella sp. D-1 (Arctic). Pharm: Antibacterial (50 μg/disk: Escherichia coli, IZ = 8 mm; Bacillus subtilis, IZ = 8 mm; Staphylococcus. aureus, IZ = 9 mm). Ref: X. L. Lu, et al, J. Antibiot., 2014, 67, 171

O HO

OH

466 Scopararane B Type: Isopimarane diterpenoids. C20H28O6 Gum, [α]D29 = +232.5° (c = 0.04, MeOH). Source: Marine-derived fungus Eutypella scoparia (sediment, South China Sea). Pharm: Cytotoxic (SF268, IC50 = 80.1 μmol/L, control Cisplatin, IC50 = 4.0 μmol/L; MCF7, IC50 = 60.1 μmol/L, Cisplatin, IC50 = 9.2 μmol/L; NCI-H460, IC50 > 100 μmol/L, Cisplatin, IC50 = 1.5 μmol/L). Ref: L. Sun, Chin. Tradit. Herb. Drugs 2011, 42, 432│L. Sun, et al, Mar. Drugs, 2012, 10, 539

150

3 Diterpenoids

HO

OH

O OH OH

O

467 Scopararane C Type: Isopimarane diterpenoids. C20H28O3 Colorless crystals, mp 170.4 °C, [α]D25 = −160.40° (c = 1.53, CHCl3). Source: Marine-derived fungus Eutypella scoparia (sediment, South China Sea). Pharm: Cytotoxic (SF268, IC50 > 100 μmol/L, control Cisplatin, IC50 = 4.0 μmol/L; MCF7, IC50 = 35.9 μmol/L, Cisplatin, IC50 = 9.2 μmol/L; NCI-H460, IC50 > 100 μmol/L, Cisplatin, IC50 = 1.5 μmol/L). Ref: L. Sun, et al, Mar. Drugs, 2012, 10, 539

OH O OH

468 Scopararane D Type: Isopimarane diterpenoids. C20H28O4 Colorless crystals, mp 197.4 °C, [α]D25 = −200.36° (c = 0.84, CHCl3). Source: Marine-derived fungus Eutypella scoparia (sediment, South China Sea). Pharm: Cytotoxic (SF268, IC50 = 43.5 μmol/L, control Cisplatin, IC50 = 4.0 μmol/L; MCF7, IC50 = 25.6 μmol/L, Cisplatin, IC50 = 9.2 μmol/L; NCI-H460, IC50 = 46.1 μmol/L, Cisplatin, IC50 = 1.5 μmol/L). Ref: L. Sun, et al, Mar. Drugs, 2012, 10, 539

OH HO

O OH

469 Scopararane E Type: Isopimarane diterpenoids. C20H28O5 Colorless crystals, mp 100.0 °C, [α]D25 = −92.30° (c = 0.77, MeOH). Source: Marine-derived fungus Eutypella scoparia (sediment, South China Sea). Pharm: Cytotoxic (SF268, IC50 > 100 μmol/L, control Cisplatin, IC50 = 4.0 μmol/L; MCF7, IC50 = 74.1 μmol/L, Cisplatin, IC50 = 9.2 μmol/L;

3.7 Isopimarane Diterpenoids

151

NCI-H460, IC50 > 100 μmol/L, Cisplatin, IC50 = 1.5 μmol/L). Ref: L. Sun, et al, Mar. Drugs, 2012, 10, 539 HO

OH HO

O OH

470 Scopararane F Type: Isopimarane diterpenoids. C20H30O5 Colorless crystals, mp 170.0 °C, [α]D25 = −94.70° (c = 0.66, MeOH). Source: Marine-derived fungus Eutypella scoparia (sediment, South China Sea). Pharm: Cytotoxic (SF268, IC50 > 100 μmol/L, control Cisplatin, IC50 = 4.0 μmol/L; MCF7, IC50 > 100 μmol/L, Cisplatin, IC50 = 9.2 μmol/L; NCI-H460, IC50 > 100 μmol/L, Cisplatin, IC50 = 1.5 μmol/L). Ref: L. Sun, et al, Mar. Drugs, 2012, 10, 539

O OH

OH OH

OH

471 Scopararane G Type: Isopimarane diterpenoids. C20H30O4 Colorless oil, [α]D25 = +1.43° (c = 0.42, MeOH). Source: Marine-derived fungus Eutypella scoparia (sediment, South China Sea). Pharm: Cytotoxic (SF268, IC50 > 100 μmol/L, control Cisplatin, IC50 = 4.0 μmol/L; MCF7, IC50 = 85.5 μmol/L, Cisplatin, IC50 = 9.2 μmol/L; NCI-H460, IC50 > 100 μmol/L, Cisplatin, IC50 = 1.5 μmol/L). Ref: L. Sun, et al, Mar. Drugs, 2012, 10, 539

OH OH

OH O

472 Tedanol Type: Isopimarane diterpenoids. C20H31Br2O5S−1 Source: Sponge Tedania ignis (Sweeting Cay, Grand Bahama I., Bahamas). Pharm: Anti-inflammatory (mice). Ref: V. Costantino, et al, BoMC, 2009, 17, 7542

152

3 Diterpenoids

Br O

S O

O O–

H Br

H

OH

473 Virescenoside A Type: Isopimarane diterpenoids. C26H42O8 Amorph., mp 130 °C, [α]D = −42.7° (c = 1.03, MeOH). Source: Marine-derived fungus Acremonium striatisporum KMM 4401 from sea cucumber Eupentacta fraudatrix, terrestrial fungus (Acremonium luzulae). Pharm: Cytotoxic (Ehrlich carcinoma cells, sea urchin eggs). Ref: N. CagnoliBellavita, et al, Gazz. Chim. Ital., 1969, 99, 1354│S. S. Afiyatullov, et al, JNP, 2000, 63, 848

HO H HO HO

OO HO

OH OH

474 Virescenoside B Type: Isopimarane diterpenoids. C26H42O7 Amorph., mp 110 °C, [α]D = −32.3° (c = 1.05, MeOH). Source: Marine-derived fungus Acremonium striatisporum KMM 4401 from sea cucumber Eupentacta fraudatrix, terrestrial fungus (Oospora virescens). Pharm: Cytotoxic (Ehrlich carcinoma cells, sea urchin eggs). Ref: S. S. Afiyatullov, et al, JNP, 2000, 63, 848; 2002, 65, 641

H HO HO

OO HO

OH OH

3.7 Isopimarane Diterpenoids

153

475 Virescenoside C Type: Isopimarane diterpenoids. C26H40O7 Cryst. (EtOAc), mp 160–162 °C, [α]D = −71.4° (c = 0.98, MeOH). Source: Marine-derived fungus Acremonium striatisporum KMM 4401 from sea cucumber Eupentacta fraudatrix, terrestrial fungus (Acremonium luzulae). Pharm: Cytotoxic (Ehrlich carcinoma cells, sea urchin eggs). Ref: S. S. Afiyatullov, et al, JNP, 2000, 63, 848; 2002, 65, 641

H O HO

OO HO

OH OH

476 Virescenoside M Type: Isopimarane diterpenoids. C26H40O9 Plates (MeOH), mp 143–146 °C, [α]D20 = +29° (c = 0.28, MeOH). Source: Marine-derived fungus Acremonium striatisporum KMM 4401 from sea cucumber Eupentacta fraudatrix (Sea of Japan). Pharm: Cytotoxic (Ehrlich carcinoma cells, IC50 = 10–100 μmol/L); cytotoxic (developing eggs of sea urchin Strongylocentrotus, MIC50 = 2.7–20 μmol/L). Ref: S. Sh. Afiyatullov, et al, JNP, 2000, 63, 848

HO

HO HO

HO

O OO HO

β -D-altropyranoside

OH

477 Virescenoside N (2α,3β,7α)-8(14),15-Isopimaradiene-2,3,7,19-tetrol 19-O-β-D-altropyranoside Type: Isopimarane diterpenoids. C26H42O9 Colorless amorphous solid, (MeOH); mp 143–146 °C, [α]D20 = –18° (c = 0.25, MeOH). Source: Marine-derived fungus Acremonium striatisporum KMM 4401 from sea cucumber Eupentacta fraudatrix. Pharm: Cytotoxic (Ehrlich carcinoma cells, IC50 = 10–100 μmol/L); toxic (developing eggs of sea urchin Strongylocentrotus, MIC50 = 2.7–20 μmol/L). Ref: S. Sh. Afiyatullov, et al, JNP, 2000, 63, 848; 2005, 68, 1308

154

3 Diterpenoids

HO

HO

OH OO HO

HO

β -D-altropyranoside

HO OH

478 Virescenoside O Type: Isopimarane diterpenoids. C26H42O8 Amorph. solid, [α]D20 = –44° (c = 0.5, MeOH). Source: Marine-derived fungus Acremonium striatisporum KMM 4401 from sea cucumber Eupentacta fraudatrix. Pharm: Cytotoxic (Ehrlich carcinoma cells, IC50 = 10–100 μmol/L); cytotoxic (sea urchin eggs). Ref: S. Sh. Afiyatullov, et al, JNP, 2002, 65, 641; 2004, 67, 1047

HO

OH OO HO

HO

β -D-altropyranoside

HO OH

479 Virescenoside P Type: Isopimarane diterpenoids. C26H40O8 Amorph. solid, [α]D20 = +31° (c = 0.2, MeOH). Source: Marine-derived fungus Acremonium striatisporum KMM 4401 from sea cucumber Eupentacta fraudatrix. Pharm: Cytotoxic (Ehrlich carcinoma cells, IC50 = 10–100 μmol/L). Ref: S. Sh. Afiyatullov, et al, JNP, 2002, 65, 641

HO HO HO

OO HO OH

O

β-D-altropyranoside

3.7 Isopimarane Diterpenoids

155

480 Virescenoside Q Type: Isopimarane diterpenoids. C26H42O7 Amorph. solid, [α]D20 = −20° (c = 0.45, MeOH). Source: Marine-derived fungus Acremonium striatisporum KMM 4401 from sea cucumber Eupentacta fraudatrix. Pharm: Cytotoxic (Ehrlich carcinoma cells, IC50 = 10–100 μmol/L). Ref: S. Sh. Afiyatullov, et al, JNP, 2000, 63, 848; 2002, 65, 641

H HO OO

HO

OH OH

β-D-mannopyranoside

OH

481 2-Acetoxy-15-bromo-7,16-dihydroxy-3palmitoyl-neoparguera-4(19),9(11)-diene Type: Rearranged pimarane and isopimarane diterpenoids. C38H63BrO6 Viscous oil, [α]D = −27.2° (c = 2.40, CHCl3). Source: Red alga Laurencia obtusa. Pharm: Cytotoxic (B16 cells, IC50 = 0.78 μg/mL). Ref: S. Takeda, et al, Chem. Lett., 1990, 19, 277 O O

H

OH Br

O 13

O

H

OH

482 Myrocin A Type: Rearranged pimarane and isopimarane diterpenoids. C20H22O6 Solid, [α]D22 = −418.6° (c = 0.36, MeOH). Source: Marine-derived fungi Arthrinium sp. from sponge Geodia cydonium (Adriatic Sea, Italy) and Apiospora montagnei, marine-derived fungus Apiospora montagnei (psychrophilic, cold water) from red alga Polysiphonia violacea, (inner tissue, North Sea). Pharm: Cytotoxic (L5178Y, IC50 = 2.74 μmol/L, control Kahalalide F, IC50 = 4.30 μmol/L; K562, IC50 = 42.0 μmol/L, control Cisplatin (CDDP), IC50 = 7.80 μmol/L; A2780, IC50 = 28.2 μmol/L, Cisplatin (CDDP), IC50 = 0.80 μmol/L; A2780CisR, IC50 = 154.7 μmol/L, Cisplatin (CDDP), IC50 = 8.40 μmol/L); inhibits VEGF-A dependent endothelial cell sprouting (cellular angiogenesis assay, IC50 = 3.70 μmol/L, control Sunitinib, IC50 = 0.12 μmol/L). Ref: C. Klemke, et al, JNP, 2004, 67, 1058│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)│S. S. Ebada, et al, BoMC, 2011, 19, 4644

156

3 Diterpenoids

O

OH O HOOC

OH

3.8 Dolabrane (Erythroxylane) Diterpenoids 483 Tagalsin Q Type: Dolabrane diterpenoids. C18H26O2 Cryst., mp 155–157 °C, [α]D25 = +245° (c = 0.5, MeOH). Source: Mangrove Ceriops tagal (Hainan Is., China). Pharm: Antifeedant (Brontispa longissima, an insect pest of coconut palms, moderate). Ref: W. -M. Hu, et al, JNP, 2010, 73, 1701 OH H

H

O

484 Tagalsin R Type: Dolabrane diterpenoids. C19H28O4 Amorph. powder, [α]D25 = −20° (c = 0.4, MeOH). Source: Mangrove Ceriops tagal (Hainan Is., China). Pharm: Antifeedant (Brontispa longissima, an insect pest of coconut palms, moderate). Ref: W. -M. Hu, et al, JNP, 2010, 73, 1701 O H

H

OH

O HO

485 Tagalsin U 15,16-Dihydroxy-4(18)-erythroxylen-3-one Type: Dolabrane diterpenoids. C20H32O3 Oil, [α]D25 = +5° (c = 0.2, MeOH). Source: Mangrove Ceriops tagal (Hainan Is., China). Pharm: Antifeedant (Brontispa longissima, an insect pest of coconut palms, moderate). Ref: W. -M. Hu, et al, JNP, 2010, 73, 1701

3.9 Paraguerane and Isoparguerane Diterpenoids

157

OH

H

H

OH

O

3.9 Paraguerane and Isoparguerane Diterpenoids 486 Deacetylisoparguerol Type: Paraguerane and isoparguerane diterpenoids. C20H31BrO4 Glassy solid, [α]D = +5° (c = 0.46, MeOH). Source: Red alga Laurencia obtusa. Pharm: Antifeedant. Ref: S. Takeda, et al, Bull. Chem. Soc. Jpn., 1990, 63, 3066

OH

H

HO

Br OH

H OH

487 Deoxyparguerol Deoxyparguerene Type: Paraguerane and isoparguerane diterpenoids. C22H33BrO4 Oil, [α]D = −35.8° (c = 0.62, CHCl3). Source: Sea hare Aplysia dactylomela (shallow waters, near La Parguera, Puerto Rico). Pharm: Cytotoxic (PS, ED50 = 0.38 μg/mL). Ref: F. J. Schmitz, et al, JACS, 1982, 104, 6415

OH

H

O

Br

O H

OH

488 Isoparguerol Type: Paraguerane and isoparguerane diterpenoids. C22H33BrO5 Cryst., mp 139– 141°, [α]D27 = +3.6° (c = 0.14, CHCl3). Source: Sea hare Aplysia dactylomela (shallow waters, near La Parguera, Puerto Rico). Pharm: Cytotoxic (PS, ED50 = 4.6 μg/mL). Ref: S. Yamamura, et al, Tet. Lett., 1977, 2171│F. J. Schmitz, et al, JACS, 1982, 104, 6415│S. takeda, et al, Bull. Chem. Soc. Jpn., 1990, 63, 3066

158

3 Diterpenoids

O H

O

OH Br

2

OH

H OH

489 Isoparguerol 16-acetate 16-Acetoxy-isoparguerol Type: Paraguerane and isoparguerane diterpenoids. C24H35BrO6 Cryst., mp 180–182 °C, [α]D = −18.8° (c = 0.09, CHCl3). Source: Sea hare Aplysia dactylomela (shallow waters, near La Parguera, Puerto Rico). Pharm: Cytotoxic (PS, ED50 = 0.52 μg/mL). Ref: S. Yamamura, et al, Tet. Lett., 1977, 2171│F. J. Schmitz, et al, JACS, 1982, 104, 6415│S. takeda, et al, Bull. Chem. Soc. Jpn., 1990, 63, 3066 O H

O

O Br

H

O

OH

OH

490 9(11)-Pargueren-16-al Type: Paraguerane and isoparguerane diterpenoids. C20H30O Oil, [α]D26 = 13.0° (c = 1.54, CHCl3). Source: Red alga Laurencia saitoi. Pharm: Feeding-inhibitor (young abalone Haliotis discus hannai, sea urchins Stronglyocentrotus nudus and Stronglyocentrotus intermedius). Ref: K. Kurata, et al, Phytochemistry, 1998, 47, 363 O H

H

H

491 Parguerol Parguerene Type: Paraguerane and isoparguerane diterpenoids. C22H33BrO5 Oil, [α]D = −40° (c = 0.03, CHCl3). Source: Sea hare Aplysia dactylomela (shallow waters, near La Parguera, Puerto Rico). Pharm: Cytotoxic (PS, ED50 = 3.8 μg/mL). Ref: F. J. Schmitz, et al, JACS, 1982, 104, 6415

3.10 Spongiane Diterpenoids

OH

H

O

159

Br

O

OH

H OH

492 Parguerol 16-acetate Type: Paraguerane and isoparguerane diterpenoids. C22H33BrO6 Source: Sea hare Aplysia dactylomela (shallow waters, near La Parguera, Puerto Rico). Pharm: Cytotoxic (PS, ED50 = 4.3 μg/mL). Ref: F. J. Schmitz, et al, JACS, 1982, 104, 6415 O

H

O

Br

O

O

OH

H OH

3.10 Spongiane Diterpenoids 493 19-Acetoxy-13(16),14-Spongiadiene Type: Spongiane diterpenoids. C22H32O3 Source: Sponge Spongia sp. [Syn. Heterofibria sp.]. Pharm: Immune system activity (murine spleen cell lysosome activation, IC50 (apparent) < 100 μg/mL). Ref: L. P. Ponomarenko, et al, JNP, 2007, 70, 1110 O H H O O

494 11α-Acetoxy-13-spongien-16-one Type: Spongiane diterpenoids. C22H32O4 Glass, [α]D25 = −28° (c = 0.74, CH2Cl2). Source: Sponge Dysidea cf. arenaria (Okinawa). Pharm: Cytotoxic (NBT-T2, IC50 > 10 μg/mL). Ref: M. Agena, et al, Tetrahedron, 2009, 65, 1495

160

3 Diterpenoids

O

O O O H H

495 11β-Acetoxy-13-spongien-16-one Type: Spongiane diterpenoids. C22H32O4 Glass, [α]D25 = +15° (c = 0.41, CH2Cl2). Source: Sponge Dysidea cf. arenaria (Okinawa). Pharm: Cytotoxic (NBT-T2, IC50 > 10 μg/mL). Ref: M. Agena, et al, Tetrahedron, 2009, 65, 1495 O

O O O H H

496 12-epi-Aplysillin Type: Spongiane diterpenoids. C26H40O7 [α]D25 = +8.2° (c = 0.4, CHCl3). Source: Nudibranches Chromodoris luteorosea and Chromodoris geminus. Pharm: Ichthyotoxic. Ref: E. D. De Silva, et al, JNP 1991, 54, 993 O

O O

O O O O

H

497 6α,11β-Diacetoxy-14α-hydroxy-12-spongien-16-one Type: Spongiane diterpenoids. C24H34O7 Cryst. (MeOH), [α]D25 = +250° (c = 0.28, CH2Cl2). Source: Sponge Dysidea cf. arenaria (Okinawa). Pharm: Cytotoxic (NBT-T2, IC50 = 1.9 μg/mL). Ref: M. Agena, et al, Tetrahedron, 2009, 65, 1495 O

O O O H H

OH

O O

3.10 Spongiane Diterpenoids

161

498 3,19-diacetoxy-13(16),14-Spongiadiene Type: Spongiane diterpenoids. C24H34O5 Solid, mp 84–89 °C, [α]D27 = −73° (c = 0.055, CHCl3). Source: Sponge Spongia sp. [Syn. Heterofibria sp.]. Pharm: Immune system activity (murine spleen cell lysosome activation, IC50 (apparent) < 100 μg/mL). Ref: L. P. Ponomarenko, et al, JNP, 2007, 70, 1110

O O

H O

H O

O

499 7α,11α-Diacetoxy-13-spongien-16-one Type: Spongiane diterpenoids. C24H34O6 Solid, [α]D25 = −125° (c = 0.41, CH2Cl2). Source: Sponge Dysidea cf. arenaria. Pharm: Cytotoxic (NBT-T2, IC50 > 10 μg/mL). Ref: M. Agena, et al, Tetrahedron, 2009, 65, 1495 O

O O O H O

H O

500 6α,11β-Diacetoxy-13-spongien-16-one Type: Spongiane diterpenoids. C24H34O6 Glass, [α]D25 = +95° (c = 0.47, CH2Cl2). Source: Sponge Dysidea cf. arenaria (Okinawa). Pharm: Cytotoxic (NBT-T2, IC50 > 10 μg/mL). Ref: M. Agena, et al, Tetrahedron, 2009, 65, 1495 O

O O O H H

O O

162

3 Diterpenoids

501 (11β,16α)-Epoxy-16-acetoxy-,17-O-(3-Methylbutanoyl)dihydroxy15-isocopalanal Type: Spongiane diterpenoids. C27H42O6 Glass, [α]D25 = −10° (c= 0.85, CH2Cl2). Source: Sponge Dysidea cf. arenaria (Okinawa). Pharm: Cytotoxic (NBT-T2, IC50 = 1.8 μg/mL). Ref: M. Agena, et al, Tetrahedron, 2009, 65, 1495 O O

16

O

H 11 15

H

H

17

O

H

O O

502 (11β,16α)-Epoxy-12α-hydroxy-16α-acetoxy-17-O-(3-methylbutanoyl)15-isocopalanal Type: Spongiane diterpenoids. C27H42O7 Glass, [α]D25 = −12° (c = 0.44, CH2Cl2). Source: Sponge Dysidea cf. arenaria (Okinawa). Pharm: Cytotoxic (NBT-T2, IC50 = 4.2 μg/mL). Ref: M. Agena, et al, Tetrahedron, 2009, 65, 1495 OH O 11

O O 16

H

12

15

H

17

H O

H

O O

503 Haumanamide Type: Spongiane diterpenoids. C28H37NO3 White amorphous powder, [α]D = −163.2° (c = 0.13, CHCl3). Source: Sponge Spongia sp. (Pohnpei I., Federated States of Micronesia). Pharm: Cytotoxic (KB, MIC = 5 μg/mL; LoVo, MIC = 10 μg/mL). Ref: A. T. Pham, et al, Tet. Lett., 1992, 33, 1147 N O HOOC

H

3.10 Spongiane Diterpenoids

163

504 19-Hydroxy-3-nor-2,3-seco-13(16),14-spongiadien-2,4-olide Type: Spongiane diterpenoids. C19H26O4 Powder, [α]D = +15.2° (c = 0.27, CHCl3). Source: Sponge Spongia matamata (Yap, Federated States of Micronesia). Pharm: Toxic (brine shrimp). Ref: C. -J. Li, et al, JNP, 1998, 61, 546 O

O O

OH

505 Isocopalendial (14αH)-12-Isocopalene-15,16-dial Type: Spongiane diterpenoids. C20H30O2 Cryst., mp 139–142 °C (dec), [α]D = +48° (c = 1.5, CHCl3). Source: Sponge Spongia officinalis. Pharm: Antifeedant (insects). Ref: D. S. de Miranda, et al, JOC, 1981, 46, 4851│G. Cimino, et al, Tet. Lett., 1982, 23, 4139│T. Nakano, et al, JCS Perkin I, 1983, 135│M. P. Mischne, et al, JOC, 1984, 49, 2035│T. Nakano, et al, J. Chem. Res.(S), 1984, 262 │R. Puliti, et al, Acta Crystallogr., Sect. C, 1999, 55, 2160 O O H

H

H

506 (14αH)-12-Isocopalen-15-oic acid(3-acetoxy-2-hydroxypropyl) ester Type: Spongiane diterpenoids. C25H40O5 Colorless crystals, mp 117–119 °C, [α]D = −53.7° (c = 0.21, CHCl3). Source: Sponge Acanthella montereyensis, nudibranches Archidoris tuberculata and Archidoris pseudoargus. Pharm: Ichthyotoxic. Ref: K. Gustafson, et al, Tetrahedron, 1985, 41, 1101│Soriente, et al, Nat. Prod. Lett., 1993, 3, 31│G. Cimino, et al, JNP, 1993, 56, 1642│N. Ungur, et al, Tetrahedron, 2000, 56, 2503 OH O H

O

O O

H

507 12-Isocopalen-15-oic acid (2-acetoxy-3-hydroxypropyl) ester Type: Spongiane diterpenoids. C25H40O5 Oil or colorless crystal.,mp 75–76 °C, [α]D = −33° (c = 0.83, CHCl3). Source: Sponge Acanthella montereyensis, nudibranches Archidoris tuberculata, Archidoris pseudoargus and Archidoris montereyensis. Pharm: Ichthyotoxic. Ref: K. Gustafson, et al, Tetrahedron, 1985, 41, 1101│Soriente, et al,

164

3 Diterpenoids

Nat. Prod. Lett., 1993, 3, 31│G. Cimino, et al, JNP, 1993, 56, 1642│N. Ungur, et al, Tetrahedron, 2000, 56, 2503 O O OH

O O

508 12-Isocopalen-15-oic acid2S,3-dihydroxypropyl ester Type: Spongiane diterpenoids. C23H38O4 Cryst. (Et2O/hexane), mp 125–126 °C, [α]D = −12.5° (c = 0.4, CHCl3). Source: Nudibranch Archidoris montereyensis. Pharm: Antifeedant (fish). Ref: K. Gustafson, et al, Tet. Lett., 1984, 25, 11│K. Gustafson, et al, Tetrahedron, 1985, 41, 1101│N. Ungur, et al, Tetraheedon Lett., 1996, 37, 3549

O H

O

H

OH OH

509 Isospongiadiol Type: Spongiane diterpenoids. C20H28O4 Cryst. (MeOH aq.), mp 181–183 °C, [α]D20 = −50° (c = 3.0, CH2Cl2). Source: Sponge Spongia spp. (deep water). Pharm: Cytotoxic; antiviral. Ref: S. Kohmoto, et al, Chem. Lett., 1987, 1687

O

HO H O HO

H

510 Murrayanolide Type: Spongiane diterpenoids. C25H38O6 Powder, mp 185–187 °C, [α]D25 = −16.6° (c = 0.75, CHCl3). Source: Bryozoan Dendrobeania murrayana (psychrophilic, cold water, Nova Scotia). Pharm: Metalloprotease collagenase IV inhibitor (MIC = 25 μg/ mL with 54% inhibition). Ref: C. -M. Yu, et al, JNP, 1995, 58, 1978│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)

3.10 Spongiane Diterpenoids

165

O O

H O O H

H H

O

O

511 Verrucosin 1 Type: Spongiane diterpenoids. C25H40O5 [α]D = −48.7° (c = 0.7, CHCl3). Source: Nudibranch Doris verrucosa (Mediterranean Sea). Pharm: PKC activator; morphogenetic hydra tentacle regeneration agent; tumour promoter. Ref: M. Gavagnin, et al, Tetrahedron, 1997, 53, 1491 OH O

O

O

O

512 Verrucosin 6 Type: Spongiane diterpenoids. C25H40O5 [α]D = −37.0° (c = 0.1, CHCl3). Source: Nudibranch Doris verrucosa (Mediterranean Sea). Pharm: PKC activator; morphogenetic hydra tentacle regeneration agent; tumour promoter. Ref: M. Gavagnin, et al, Tetrahedron, 1997, 53, 1491 O O O

OH

O

513 Verrucosin 7 Type: Spongiane diterpenoids. C25H41ClO5 Oil, [α]D = +19.1° (c = 0.35, CHCl3). Source: Nudibranch Doris verrucosa (Mediterranean Sea). Pharm: PKC activator; morphogenetic hydra tentacle regeneration agent. Ref: M. Gavagnin, et al, Tetrahedron, 1997, 53, 1491 Cl

OH O

O

O

O

166

3 Diterpenoids

514 Verrucosin 9 Type: Spongiane diterpenoids. C25H41ClO5 Oil, [α]D = +25.0° (c = 0.04, CHCl3). Source: Nudibranch Doris verrucosa (Mediterranean Sea). Pharm: PKC activator; morphogenetic hydra tentacle regeneration agent. Ref: M. Gavagnin, et al, Tetrahedron, 1997, 53, 1491 O Cl

O O

OH

O

515 Verrucosin A Type: Spongiane diterpenoids. C25H40O5 [α]D = +37.3° (c = 1.1, CHCl3). Source: Nudibranch Doris verrucosa. Pharm: Ichthyotoxic. Ref: G. Cimino, et al, Tetrahedron, 1988, 44, 2301│M. Gavagnin, et al, Tet. Lett., 1990, 31, 6093 OH

H

O

O

S

O

O

516 Verrucosin B Type: Spongiane diterpenoids. C25H40O5 Cryst. (Et2O/hexane), mp 118–120 °C, [α]D = +19.2° (c = 0.5, CHCl3). Source: Nudibranch Doris verrucosa. Pharm: Ichthyotoxic. Ref: G. Cimino, et al, Tetrahedron, 1988, 44, 2301│M. Gavagnin, et al, Tet. Lett., 1990, 31, 6093 O O

H

OH

O R

O

517 12-Acetoxytetrahydrosulphurin I Type: Seco-, nor- and abeo-spongiane diterpenoids. C24H34O7 Source: Sponge Aplysilla sp. Pharm: Phospholipase A2 inhibitor. Ref: B. C. M. Potts, et al, JNP, 1992, 55, 1701

3.10 Spongiane Diterpenoids

167

O O

O H

12 11 8 7

O 1316 14

H

O

O H

O

518 Aplysulphuride Tetrahydroaplysulphurin 1 Type: Seco-, nor- and abeo-spongiane diterpenoids. C22H32O5 Cryst. (CH2Cl2/hexane), mp 109 °C, [α]D = +169° (c = 1, CHCl3). Source: Sponges Spongionella sp. and Darwinella oxeata, dorid nudibranch Cadlina luteomarginata. Pharm: Kinase EGFR Inhibitor (100 μmol/L, InRt = 70%); cytotoxic (K562 hmn chronic myelogenous leukemia cell lines, IC50 = 2.3 μmol/L; PBMC hmn peripheral blood mononuclear cells, IC50 = 4.5 μmol/L). Ref: P. Karuso, et al, Aust. J. Chem., 1984, 37, 1081; 1986, 39, 1643│J. S. Buckleton, et al, Acta Cryst. C, 1987, 43, 2430│M. E. Rateb, et al, JNP 2009, 72, 1471 O H

O 16

H

O

O H

O

519 Chelonaplysin C Type: Seco-, nor- and abeo-spongiane diterpenoids. C22H32O5 Crystal, (Hexane/ Et2O), mp 148 °C, [α]D = −6.1° (c = 0.23, CHCl3). Source: Sponges Chelonaplysilla spp. Pharm: Ichthyotoxin. Ref: S. C. Bobzin, et al, JNP, 1991, 54, 225│R. Puliti, et al, Acta Cryst., Sect. C., 1992, 48, 2145 O O

O H O

O

H

520 Chromodorolide A Type: Seco-, nor- and abeo-spongiane diterpenoids. C24H34O8 Cryst. (MeOH), mp 133–134 °C, [α]D = −74° (c = 0.1, CH2Cl2). Source: An unidentified sponge (Australia), nudibranch Chromodoris cavae. Pharm: Cytotoxic (P388, InRt = 66%); Nematocidal

168

3 Diterpenoids

(two important pathogens of sheep and other ruminants: larval stages of parasitic nematodes Haemonchus contortus, 100 μg/mL, InRt = 94%, 10 μg/mL, InRt = 0%; Trichostrongylus colubriformis, 100 μg/mL, InRt = 95%, 10 μg/mL, InRt = 33%). Ref: E. J. Dumdei, et al, JACS, 1989, 111, 2712│W. Rungprom, et al, Mar. Drugs, 2004, 2, 101 O

O HO O

O H

O

O O

H H H

521 Gracilin A Type: Seco-, nor- and abeo-spongiane diterpenoids. C23H34O5 Oil, [α]D = −60.5° (c = 1.3, CHCl3). Source: Sponges Spongionella sp. (West Angaur, Philippines), Spongionella gracilis and Aplysilla tango. Pharm: Cytotoxic (K562, IC50 = (0.6 ± 0.2) μmol/L; PBMC, IC50 = (0.8 ± 0.4)μmol/L); EGFR tyrosine kinase inhibitor (incubation with 100 μmol/L, InRt = 65%, control Genistein, InRt = 80%); phospholipase A2 inhibitor; anti-AD preclinical trial (Target: Mitochondrial targeting through the induction of Nrf2 translocation; BACE1 and ERK inhibition; τ hyperphosphorylation reduction. Animal Model: 3xTg-AD mice. Effects: After chronic intraperitoneal treatments, a preliminary behavioral test pointed a positive trend on learning and spatial memory of mice treated with these compounds. Moreover, in vivo assays confirmed the previous results. Amyloid-β42 and hyperphosphorylated τ levels were decreased after treatments and the ERK inhibition was also observed) (Russo, 2016). Note: Alzheimer’s Disease (AD/Creutzfeldt-Jacob disease/CJD/CJ) is a multifactorial neurodegenerative disorder. Main scientific hypotheses are: (i) “The amyloid cascade hypothesis”: For decades the hypothesis was the main “framework” for AD research. The pathological accumulation of Aβ, as amyloid plaques, frequently observed in AD brains, was considered the main etiopathology cause. According to this hypothesis, the increased Aβ accumulation triggers a cascade of events leading to synaptic dysfunction, memory loss and structural brain damage. Now, the hypothesis that Aβ peptides is considered an oversimplification and the linear toxicity model is considered incorrect. The possible Aβ role is to trigger other downstream events, such as τ aggregation. The failure of Aβ-targeted clinical trials supports the hypothesis that Aβ peptides may be recurrent contributors in the AD process, but it is neither necessary, nor sufficient. (ii) “The cholinergic hypothesis” The hypothesis is based on the observation of significant loss in cholinergic signaling such as a severe loss of brain white matter with the reduction of cholinergic neurons of the basal forebrain (i.e., Acetylcholine (ACh), nicotine/muscarinic binding

3.10 Spongiane Diterpenoids

169

sites (nicotinic/muscarinic receptor: nAChR, mAChR)) observed in post-mortem cerebral cortex of AD patients. (iii) “The glutamatergic hypothesis” The hypothesis is based on the gradual deterioration of proper synaptic functioning through GluN2Acontaining N-methyl-D-aspartate receptors (NMDARs) and the development of excitotoxicity through GluN2B-containing NMDARs. Alteration in NMDARs activity may involve Aβ-induced synaptic impairment, spine loss and neurodegeneration. (iv) “The mitochondrial hypothesis” The hypothesis predicts that mitochondrial dysfunctions trigger energy metabolism impairment, with excessive reactive oxygen species (ROS) formation and consequent DNA damage. (v) “The metabolic hypothesis” The hypothesis is based on the assumption that mitochondrial dysregulation up-regulates the oxidative phosphorylation (OXPHOS) activity (known as “inverse Warburg effect”). (vi) “The τ hypothesis” The τ hypothesis is based on the observation that τ dysfunction （abnormal levels, hyperphosphorylation, or ubiquination), in the absence of amyloid pathology, is sufficient to cause synaptic and neuronal loss. (vii) “The memory kinase hypothesis” The hypothesis is based on the involvement of Protein Kinase C (PKC) in acquisition and modification of dendritic spines, in neurite retraction and in synaptic plasticity. (viii) “The neuro-inflammation hypothesis” The hypothesis implies an innate immune response characterized by the release of inflammatory mediators. (ix) “The clearance systems hypothesis” The hypothesis is based on Aβ clearance failure. (x) “The Cognitive Reserve (CR) hypothesis” The hypothesis is proposed to explain the gap between the brain insult and the pathological manifestations. (xi) “The disconnection hypothesis”. The hypothesis is based on the disrupted functional connectivity in AD brains association (Russo, 2016). Ref: L. Mayol, et al, Tet. Lett., 1985, 26, 1357│L. Mayol, et al, Tetrahedron, 1986, 42, 5369│T. F. Molinski, et al, JOC, 1987, 52, 296│L. Mayol, et al, Gazz. Chim. Ital., 1988, 118, 559│A. Poiner, et al, Aust. J. Chem., 1990, 43, 1713│M. E. Rateb, et al, JNP, 2009, 72, 1471│P. Russo, et al, Mar. Drugs, 2016, 14, 5 (review) O H

O 16

11 9

O H

15

O

O

522 Gracilin H Type: Seco-, nor- and abeo-spongiane diterpenoids. C22H28O8 Colorless crystals (MeOH), mp 120.4 °C, [α]D20 = +280° (c = 0.1, MeOH). Source: Sponge Spongionella sp. (West Angaur, Philippines). Pharm: Kinase EGFR inhibitor (100 μmol/L, InRt = 30%); cytotoxic (K562, IC50 = (4.5 ± 0.5)μmol/L; PBMC, IC50 = (6.5 ± 1.5)μmol/L);

170

3 Diterpenoids

EGFR tyrosine kinase inhibitor (incubation with 100 μmol/L, InRt = 30%, control Genistein, InRt = 80%). Ref: M. E. Rateb, et al, JNP, 2009, 72, 1471 H

O

O

H

O

H O

H

O

O

O

O

523 Gracilin I Type: Seco-, nor- and abeo-spongiane diterpenoids. C22H28O8 Colorless crystals (MeOH), mp 120.4 °C, [α]D20 = +280° (c = 0.1, MeOH). Source: Sponge Spongionella sp. (West Angaur, Philippines). Pharm: Kinase EGFR Inhibitor (100 μmol/L, InRt = 30%); cytotoxic (K562, IC50 = (4.5 ± 0.5)μmol/L; PBMC, IC50 = (6.5 ± 1.5)μmol/L); EGFR tyrosine kinase inhibitor (incubation with 100 μmol/L, InRt = 30%, control Genistein, InRt = 80%). Ref: M. E. Rateb, et al, JNP, 2009, 72, 1471 H

O

O

H

O

H O

H

O

O

O

O

524 Gracilin J Type: Seco-, nor- and abeo-spongiane diterpenoids. C24H32O10 Colorless oil, [α]D20 = +120° (c = 0.1, MeOH). Source: Sponge Spongionella sp. (West Angaur, Philippines). Pharm: Cytotoxic (K562, IC50 = (15 ± 1)μmol/L; PBMC, IC50 = (30 ± 10)μmol/L); EGFR tyrosine kinase inhibitor (incubation with 100 μmol/L, InRt = 25%, control Genistein, InRt = 80%). Ref: M. E. Rateb, et al, JNP, 2009, 72, 1471 O

O

O

O H H

O

O

O

O O

O

525 Gracilin K Type: Seco-, nor- and abeo-spongiane diterpenoids. C21H30O8 Colorless oil, [α]D20 = +150° (c = 0.1, MeOH). Source: Sponge Spongionella sp. (West Angaur,

3.10 Spongiane Diterpenoids

171

Philippines). Pharm: Kinase EGFR inhibitor (100 μmol/L, InRt = 19%); cytotoxic (K562, IC50 = (8.5 ± 0.5)μmol/L; PBMC, IC50 = (9 ± 1)μmol/L); EGFR tyrosine kinase inhibitor (incubation with 100 μmol/L, InRt = 19%, control Genistein, InRt = 80%). Ref: M. E. Rateb, et al, JNP, 2009, 72, 1471 H

O

O

H

H

O

H O

H

O O

O

O

526 Gracilin L Type: Seco-, nor- and abeo-spongiane diterpenoids. C23H34O6 Colorless oil, [α]D20 = +170° (c = 0.1, MeOH). Source: Sponge Spongionella sp. (West Angaur, Philippines). Pharm: Cytotoxic (K562, IC50 = (2.65 ± 0.05)μmol/L; PBMC, IC50 = (3.0 ± 0.5)μmol/L); EGFR tyrosine kinase inhibitor (incubation with 100 μmol/L, InRt = 75%, control Genistein, InRt = 80%). Ref: M. E. Rateb, et al, JNP, 2009, 72, 1471 O OH H

O O

H

O O

527 Macfarlandin A Type: Seco-, nor- and abeo-spongiane diterpenoids. C21H26O5 Cryst. (Et2O/hexane), mp 183–184 °C, [α]D = +189° (c = 0.65, CHCl3). Source: Nudibranches Chromodoris macfarlandi and Chromodoris luteorosea. Pharm: Ichthyotoxic, antimicrobial. Ref: T. F. Molinski, et al, JOC, 1986, 51, 2601│G. Cimino, et al, JNP, 1990, 53, 102 O

15

O O

O

O

528 Macfarlandin B Type: Seco-, nor- and abeo-spongiane diterpenoids. C21H26O5 Glass, [α]D = −128° (c = 0.99, CHCl3). Source: Nudibranch Chromodoris macfarlandi. Pharm:

172

3 Diterpenoids

Antimicrobial. Ref: T. F. Molinski, et al, JOC, 1986, 51, 2601│G. Cimino, et al, JNP, 1990, 53, 102 O O

15

O O

O

529 Macfarlandin D Type: Seco-, nor- and abeo-spongiane diterpenoids. C22H32O5 Needles (Et2O/hexane), mp 190–191 °C, [α]D = −169° (c = 1.2, CHCl3). Source: Nudibranch Chromodoris macfarlandi. Pharm: Antibacterial (Bacillus subtilis). Ref: T. F. Molinski, et al, JOC, 1986, 51, 4564 O O O O O H

530 Membranolide C Type: Seco-, nor- and abeo-spongiane diterpenoids. C23H34O4 Oil, [α]D25 = −100.8° (c = 0.6, CHCl3). Source: Sponge Dendrilla membranosa (psychrophilic, cold water, Anvers I., Antarctica). Pharm: Antibacterial (gram-negative bacteria); antifungal. Ref: S. Ankisetty, et al, JNP, 2004, 67, 1172│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) O 16

O

O

OH

531 Membranolide D Type: Seco-, nor- and abeo-spongiane diterpenoids. C23H34O4 Oil, [α]D25 = +6.5° (c = 0.6, CHCl3). Source: Sponge Dendrilla membranosa (psychrophilic, cold water, Anvers I., Antarctica). Pharm: Antibacterial (gram-negative bacteria); antifungal. Ref: S. Ankisetty, et al, JNP, 2004, 67, 1172│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)

3.10 Spongiane Diterpenoids

173

O 16

O

O

OH

532 Norrisolide Type: Seco-, nor- and abeo-spongiane diterpenoids. C22H32O5 Cryst., mp 144.5–146 ° C, 138–140 °C, [α]D = +1° (c = 1, CHCl3). Source: Sponges Chelonaplysilla violacea, Dendrilla sp. and Dysidea spp., nudibranch Chromodoris norrisi. Pharm: Phospholipase A inhibitor; anti-inflammatory; ichtyotoxic. Ref: J. E. Hochlowski, et al, JOC, 1983, 48, 1141│A. Rudi, et al, Tetrahedron, 1990, 46, 4019│G. Guizzunti, et al, BoMC, 2010, 18, 2115 O O H

O H

H

O

H

O

533 3ʹ-Norspongiolactone Type: Seco-, nor- and abeo-spongiane diterpenoids. C24H36O4 Colorless oil, [α]D20 = +22° (c = 0.1, MeOH). Source: Sponge Spongionella sp. (West Angaur, Philippines). Pharm: Cytotoxic (K562, IC50 = (12 ± 1)μmol/L; PBMC, IC50 = (30 ± 10) μmol/L); EGFR tyrosine kinase inhibitor (incubation with 100 μmol/L, InRt = 60%, control Genistein, InRt = 80%). Ref: M. E. Rateb, et al, JNP, 2009, 72, 1471

H

O

O

H O H

O

534 Verrucosin 3 Type: Seco-, nor- and abeo-spongiane diterpenoids. C25H40O5 [α]D = +46.8° (c = 2.4, CHCl3). Source: Nudibranch Doris verrucosa (Mediterranean Sea). Pharm: PKC activator; morphogenetic hydra tentacle regeneration agent; tumour promoter. Ref: M. Gavagnin, et al, Tetrahedron, 1997, 53, 1491

174

3 Diterpenoids

OH O

O

O

O

535 Verrucosin 8 Type: Seco-, nor- and abeo-spongiane diterpenoids. C25H40O5 [α]D = +41.5° (c = 0.05, CHCl3). Source: Nudibranch Doris verrucosa (Mediterranean Sea). Pharm: PKC activator; morphogenetic hydra tentacle regeneration agent. Ref: M. Gavagnin, et al, Tetrahedron, 1997, 53, 1491 O O O

OH

O

3.11 Podocarpane Diterpenoids 536 Verrucosin 2 Type: Podocarpane diterpenoids. C25H40O5 [α]D = −4.8° (c = 0.75, CHCl3). Source: Nudibranch Doris verrucosa (Mediterranean Sea). Pharm: PKC activator; morphogenetic hydra tentacle regeneration agent; tumour promoter. Ref: M. Gavagnin, et al, Tetrahedron, 1997, 53, 1491 OH

H

O O

O O

3.12 Phyllocladane Diterpenoids 537 Agallochaol K Type: Phyllocladane diterpenoids. C20H30O3 Colorless oil, [α]D27 = −46.7° (c = 0.45, MeOH). Source: Mangrove Excoecaria agallocha (stems and twigs, Guangxi province, China). Pharm: Anti-inflammatory (100 μmol/L, Inhibits pro-inflammatory cytokine TNFα released from Raw 264.7 cells, InRt = 40.3% (4h), 46.0% (16h); blocker of NF-

3.12 Phyllocladane Diterpenoids

175

κB activation; blocker of AP-1 activation. Ref: Y. Li, et al, Phytochemistry, 2010, 71, 2124 O HO

OH

H H

538 Agallochaol O Type: Phyllocladane diterpenoids. C29H36O5 White amorphous solid, [α]D27 = −53.3° (c = 0.15, MeOH). Source: Mangrove Excoecaria agallocha (stems and twigs, Guangxi province, China). Pharm: Anti-inflammatory (100 μmol/L, Inhibits pro-inflammatory cytokine TNFα released from Raw 264.7 cells, InRt = 44.5% (4h), 48.2% (16h); blocker of NF-κB activation. Ref: Y. Li, et al, Phytochemistry, 2010, 71, 2124 OH H O

O

OH O

H

539 Agallochaol P Type: Phyllocladane diterpenoids. C20H33O3 White amorphous solid, [α]D27 = −59.2° (c = 0.12, MeOH). Source: Mangrove Excoecaria agallocha (stems and twigs, Guangxi province, China). Pharm: Anti-inflammatory (100 μmol/L, Inhibits pro-inflammatory cytokine TNFα released from Raw 264.7 cells, InRt = 19.8% (4h), 26.6% (16h); blocker of NF-κB activation. Ref: Y. Li, et al, Phytochemistry, 2010, 71, 2124

O H HO

OH

H

540 Agallochaol Q Type: Phyllocladane diterpenoids. C20H32O2 Colorless oil, [α]D27 = −45.0° (c = 0.20, MeOH). Source: Mangrove Excoecaria agallocha (stems and twigs, Guangxi province, China). Pharm: Anti-inflammatory (100 μmol/L, Inhibits pro-inflammatory cytokine TNFα released from Raw 264.7 cells, InRt = 41.0% (4h), 35.6% (16h); blocker of NF-κB activation; blocker of AP-1 activation. Ref: Y. Li, et al, Phytochemistry, 2010, 71, 2124

176

3 Diterpenoids

O HO

H H

541 ent-17-Hydroxykaur-15-en-3-one Type: Phyllocladane diterpenoids. C20H30O2 Colorless needles, mp 143–145 °C. Source: Mangrove Excoecaria agallocha (stems and twigs, Guangxi province, China). Pharm: Anti-inflammatory (100 μmol/L, Inhibits pro-inflammatory cytokine TNFα released from Raw 264.7 cells, InRt = 29.5% (4h), 30.3% (16h); blocker of NF-κB activation. Ref: T. Konishi,et al, CPB, 1998, 46, 1393│Y. Li, et al, Phytochemistry, 2010, 71, 2124

H O

OH

H

542 ent-Kaur-15-en-3β,17-diol Type: Phyllocladane diterpenoids. C20H32O2 Source: Mangrove Excoecaria agallocha (stems and twigs, Guangxi province, China). Pharm: Anti-inflammatory (100 μmol/L, Inhibits pro-inflammatory cytokine TNFα released from Raw 264.7 cells, InRt = 34.3% (4h), 41.2% (16h); blocker of NF-κB activation. Ref: G. Palazzino, et al, 1997, Gazz. Chim. Ital. 127, 311│Y. Li, et al, Phytochemistry, 2010, 71, 2124

H HO

OH

H

3.13 Cembrane Diterpenoids 543 (1R,3Z,7E,11E,14S)-18-Acetoxy-3,7,11,15(17)-cembratetraen-16,14-olide Type: Cembrane diterpenoids. C22H30O4 Oil. Source: Soft corals Lobophytum crassum and Lobophytum durum. Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L, significantly inhibits iNOS and COX-2 protein expression; but for inhibition of β-actin protein with cytotoxic activity); antibacterial (Salmonella enteritidis, 250 μmg/disk, significant; control ampicillin, 250

3.13 Cembrane Diterpenoids

177

μg/disk, significant). Ref: Z. Kinamoni, et al, Tetrahedron, 1983, 39, 1643│S. -Y. Cheng, et al, Tetrahedron, 2008, 64, 9698│W. Zhang, et al, JNP, 2008, 71, 961 O

O

H

1R

14S

O

O

544 9-Acetoxy-5,8:12,13-diepoxycembr-15(17)—en-16,4-olide Type: Cembrane diterpenoids. C22H32O6 Source: Soft coral Sinularia capillosa. Pharm: Cytotoxic (P388, ED50 = 2.5 μg/mL; L1210, ED50 = 5.0 μg/mL). Ref: J. Y. Su, et al, JNP, 63, 1543 O

O O

O H

O O

545 18-Acetoxy-3R,4S-epoxy-13R-Hydroxy-7,11,15(17)-cembratrien-16,14-olide Type: Cembrane diterpenoids. C22H30O6 Oil, [α]D24 = −81° (c = 1.3, CHCl3). Source: Soft corals Lobophytum durum and Lobophytum crassum. Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L, doesn’t inhibit up-regulation of pro-inflammatory COX-2, but inhibis iNOS to 0.2%, compare with control LPS-stimulated cells alone; 10 μmol/L, mouse keeping protein β-actin is not changed); antibacterial (Salmonella enteritidis, 50 μg/disk, significant; control Ampicillin, 250 μg/disk, significant). Ref: Y. Kashman, et al, JOC, 1981, 46, 3592│S. -Y. Cheng, et al, Tetrahedron, 2008, 64, 9698 O O O HO H R

O

O

546 18-Acetoxy-3R,4S-epoxy-13S-Hydroxy-7,11,15(17)-cembratrien-16,14-olide Type: Cembrane diterpenoids. C22H30O6 Oil, [α]D24 = +16° (c = 0.9, CHCl3). Source: Soft corals Lobophytum durum and Lobophytum crassum. Pharm: Anti-

178

3 Diterpenoids

inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L, significantly inhibits iNOS and COX-2 protein expression; but for inhibition of β-actin protein with cytotoxic activity); antibacterial (Salmonella enteritidis, 100 μg/disk, significant; control Ampicillin, 250 μg/disk, significant). Ref: Y. Kashman, et al, JOC, 1981, 46, 3592│S. -Y. Cheng, et al, Tetrahedron, 2008, 64, 9698 O O O HO H S

O

O

547 13-Acetoxysarcocrassolide Type: Cembrane diterpenoids. C22H30O5 Colorless oil, [α]D25 = +56.6° (c = 0.19, CHCl3). Source: Soft coral Sarcophyton crassocaule (Taiwan Waters). Pharm: Cytotoxic (A549, EC50 = 4.66 μg/mL, HT29, EC50 = 5.67 μg/mL, KB, EC50 = 7.39 μg/ mL, P388, EC50 = 0.38 μg/mL). Ref: C. -Y. Duh, et al, JNP, 2000, 63, 1634 O O O O

O

548 13-Acetoxysarcophytoxide Type: Cembrane diterpenoids. C22H32O4 Colorless oil, [α]D25 = +14° ( c = 0.1, CHCl3). Source: Soft coral Lobophytum crassum (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (A549, ED50 = 3.6 μg/mL, control Mithramycin, ED50 = 0.18 μg/ mL; HT29, ED50 = 10 μg/mL, Mithramycin, ED50 = 0.21 μg/mL; P388, ED50 = 28 μg/ mL, Mithramycin, ED50 = 0.15 μg/mL). Ref: S. -T. Lin, et al, Mar. Drugs, 2011, 9, 2705 O O O O

3.13 Cembrane Diterpenoids

179

549 Acetylehrenberoxide B Type: Cembrane diterpenoids. C22H36O4 Source: Soft coral Sarcophyton ehrenbergi (Sansiantai, Taitung county, Taiwan). Pharm: Cytotoxic (P388, mild); antiviral (hmn cytomegalovirus). Ref: S. -K. Wang, et al, Mar. Drugs, 2013, 11, 4318

O

O O HO

550 Asperdiol Type: Cembrane diterpenoids. C20H32O3 Cryst. (Me2CO/hexane), mp 109–110 °C, [α]D20 = −87° (CHCl3). Source: Annelida Eunicea asperula and Eunicea tourneforti. Pharm: Cytotoxic (P388, ED50 = 6 μg/mL; L1210, ED50 = 6 μg/mL). Ref: A.J. Weinheimer, et al, Tet. Lett., 1977, 1295│G. E. Martin, et al, Tet. Lett., 1979, 2195│W. C. Still, et al, JOC, 1983, 48, 4785 OH

O

HO

551 Bipinnatin A Lophotoxin-analog V Type: Cembrane diterpenoids. C25H28O11 [α]D20 = −76.6° (c = 3.5, CH2Cl2). Source: Gorgonian Pseudopterogorgia bipinnata. Pharm: Cytotoxic. Ref: A. E. Wright, et al, Tet. Lett., 1989, 30, 3491 O O O O O H

O O

O O

O O

552 Bipinnatin B Lophotoxin-analog I Type: Cembrane diterpenoids. C24H26O10 [α]D20 = −68.9° (c = 1.2, CH2Cl2). Source: Gorgonian Pseudopterogorgia bipinnata. Pharm: Cytotoxic; irreversibly inhibits binding of α-toxin to nicotinic acetylcholine receptor. Ref: A. E. Wright, et al, Tet. Lett., 1989, 30, 3491

180

3 Diterpenoids

O O O O O H

O O

O O

O

553 Bipinnatin D Type: Cembrane diterpenoids. C24H26O9 [α]D20 = +34.2° (c = 0.17, CH2Cl2). Source: Gorgonian Pseudopterogorgia bipinnata. Pharm: Cytotoxic. Ref: A. E. Wright, et al, Tet. Lett., 1989, 30, 3491 O O O O O H

O O O

O

554 Calyculaglycoside A Type: Cembrane diterpenoids. C30H48O8 Oil, [α]D24 = +9.2° (c = 0.6, CHCl3). Source: Annelida Eunicea sp. (Columbia). Pharm: Anti-inflammatory; inhibits synthesis of prostaglandin PGE2 and leukotriene LTB4. Ref: O. M. Cóbar, et al JOC, 1997, 62, 7183│Y. P. Shi, et al, JNP, 2001, 64, 1439 O O HO

O

H O

O

OH

O

555 Calyculaglycoside B Type: Cembrane diterpenoids. C30H48O8 Oil, [α]D26 = +11.4° (c = 0.5, CHCl3). Source: Annelida Eunicea sp. (Columbia). Pharm: Cytotoxic (majority of NCI ovarian cancer lines and several of renal, prostate and colon tumor lines, LC50 = 10−4– 10−5 mol/L); anti-inflammatory; inhibits synthesis of prostaglandin PGE2 and leukotriene LTB4. Ref: O. M. Cóbar, et al JOC, 1997, 62, 7183│Y. P. Shi, et al, JNP, 2001, 64, 1439

3.13 Cembrane Diterpenoids

181

O O HO

O

O OH H O

O

556 Calyculaglycoside C Type: Cembrane diterpenoids. C30H48O8 Oil, [α]D24 = +7.8° (c = 0.5, CHCl3). Source: Annelida Eunicea sp. (Columbia). Pharm: Cytotoxic (majority of NCI ovarian cancer lines and several of renal, prostate and colon tumor lines, LC50 > 10−4–10−5 mol/L); anti-inflammatory. Ref: O. M. Cóbar, et al JOC, 1997, 62, 7183│Y. P. Shi, et al, JNP, 2001, 64, 1439 O O HO

O

H

O

OH O O

557 Capillolide 3,4,11-Trihydroxy-7,15(17)-cembradien-16,12-olide Type: Cembrane diterpenoids. C20H32O5 Cryst., mp 158–160 °C, [α]D25 = +42.8° (c = 0.05, EtOH). Source: Soft corals Sinularia sp. (Dongluo I., Hainan, South China Sea), Sinularia capillosa, Sinularia microclavata and Sinularia tenella. Pharm: Cytotoxic (P388, ED50 = 15.0 μg/mL; L1210, ED50 = 18.5 μg/mL). Ref: J. S. Yang, et al, JNP, 2000, 63, 1543│R. -L. Yang, et al, Huaxue Xuebao, 2000, 58, 1186│C. -W. Lin, et al, Chem. Res. Chin. Univ., 2002, 18, 189│C. -X. Zhang, et al, Acta Cryst. E, 2004, 60, o1598│B. Yang, ET AL, Mar. Drugs, 2012, 10, 2023 OH

O

OH

O

OH

558 Cembranoid JNP98-237 Type: Cembrane diterpenoids. C21H32O3 Clear oil, [α]D = +56° (c = 0.008, CHCl3). Source: Soft coral Lobophytum crassum (Great Barrier Reef). Pharm: Antifungal (Ustilago violacea). Ref: G. F. Matthée, et al, JNP, 1998, 61, 237

182

3 Diterpenoids

O

H

O O

559 (1S,2S,3E,7E,11E)-3,7,11,15-Cembratetraen-17,2-olide Type: Cembrane diterpenoids. C20H28O2 Source: Soft coral Lobophytum sp. (Vietnam). Pharm: Cytotoxic (A549, IC50 = 5.1 μmol/L, control Mitoxantrone, IC50 = 6.1 μmol/L; HT29, IC50 = 1.8 μmol/L, control Mitoxantrone, IC50 = 6.5 μmol/L). Ref: H. T. Nguyen, et al, Arch. Pharm. Res. 2010, 33, 503 O

3E

O

7E 2 1

11E

560 Cembrene A (all-E)-3,7,11,15-Cembratetraene Type: Cembrane diterpenoids. C20H32 Oil, bp0.8mmHg 150–152 °C, [α]D = −19.7° (CHCl3). Source: Soft coral Sinularia flexibilis and other corals, mainly found in higher plants. Pharm: Cytotoxic (KB, ED50 = 2.8 μg/mL, P388, ED50 = 0.31 μg/mL, L1210, ED50 = 0.22 μg/mL). Ref: M. H. G. Munro, et al, in P. J. Scheuer eds. Bioorganic Marine Chemistry, 1987, New York: Springer-Verlag, 93– 165

561 Claviolide Type: Cembrane diterpenoids. C24H32O6 Oil, [α]D25 = −33.8° (c = 0.05, CHCl3). Source: Stolonifer Clavularia violacea (Taiwan Waters). Pharm: Cytotoxic (A549, ED50 = 4.91 μg/mL; HT29, ED50 = 0.84 μg/mL; P388, ED50 = 0.38 μg/mL). Ref: C. -Y. Duh, et al, JNP, 2002, 65, 1535

3.13 Cembrane Diterpenoids

183

O O

O

O

O O

562 Crassarine F Type: Cembrane diterpenoids. C20H32O2 Colorless oil; [α]D24 = −63° (c = 0.18, CHCl3). Source: Soft coral Sinularia crassa (Sansiantai, Taitung County, Taiwan). Pharm: Anti-inflammatory (immunoblot analysis assay, RAW264.7 macrophage cells, 10 μmol/L, inhibition of LPS induced upregulation of COX-2, Inhibited COX-2 = (65.6 ± 6.2)%, P < 0.05; control Caffeic acid phenethyl ester 10 μmol/L, Inhibited COX-2 = (75.6 ± 12.2)%). Ref: C. -H. Chao, et al, Mar. Drugs, 2011, 9, 1955

HO O

563 Crassarine H Type: Cembrane diterpenoids. C20H30O2 Colorless oil; [α]D24 = −12° (c = 0.22, CHCl3). Source: Soft coral Sinularia crassa (Sansiantai, Taitung County, Taiwan). Pharm: Anti-inflammatory (immunoblot analysis assay, RAW264.7 macrophage cells, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, Inhibited iNOS = (35.8 ± 10.7)%, P < 0.05; control Caffeic acid phenethyl ester 10 μmol/L, Inhibited iNOS = (0.8 ± 4.5)%). Ref: C. -H. Chao, et al, Mar. Drugs, 2011, 9, 1955

O

O

564 Crassin acetate Type: Cembrane diterpenoids. C22H32O5 Cryst., mp 138–140 °C, [α]D = +70.4°. Source: Gorgonians Pseudoplexaura porosa and pseudoplexaura spp. Pharm:

184

3 Diterpenoids

Cytotoxic (inhibits cell division of fertilized sea urchin eggs, 16 μg/mL); Cytotoxic (KB, ED50 = 2.0 μg/mL; L1210, ED50 = 0.2 μg/mL); antineoplastic (in vivo, P388, 50 μg/ kg, T/C = 130); ichthyotoxin. Ref: M. H. G. Munro, et al, in P. J. Scheuer eds. Bioorganic Marine Chemistry, 1987, New York: Springer-Verlag, 93–165 OH

O

O O O

565 Crassocolide H (1R,3E,7E,11S,12R,14S)-11-Chloro-12-hydroxy-3,7,15(17)-cembratrien-16,14-olide Type: Cembrane diterpenoids. C20H29ClO3 Oil, [α]D25 = +7.5° (c = 0.4, CHCl3). Source: Soft coral Sarcophyton crassocaule (Taiwan Waters). Pharm: Cytotoxic (KB cells, IC50 = 5.3 μg/mL, control Mitomycin, IC50 = 0.08 μg/mL; HeLa, IC50 = 14.9 μg/mL, Mitomycin, IC50 = 0.06 μg/mL; Daey, IC50 = 3.8 μg/mL, Mitomycin, IC50 = 0.05 μg/ mL). Ref: H. -C. Huang, et al, Chem. Biodivers., 2009, 6, 1232

1R

Cl

14S

O

12R

11S

OH

O

566 Crassocolide I (1R,3R,4S,7E,11E,13S,14R)-3,4-Dihydroxy-13-acetoxy-7,11,15(17)-cembratrien-16,14olide Type: Cembrane diterpenoids. C22H32O6 Oil, [α]D25 = −33° (c = 0.4, CHCl3). Source: Soft coral Sarcophyton crassocaule (Taiwan Waters). Pharm: Cytotoxic (Doay cells, IC50 = 0.8 μg/mL; control Mitomycin, IC50 = 0.05 μg/mL; KB, IC50 > 20 μg/mL; HeLa, IC50 > 20 μg/mL). Ref: H. C. Huang, et al, Chem. Biodivers., 2009, 6, 1232 OH

OH

3

O

13

O O O

3.13 Cembrane Diterpenoids

185

567 Crassocolide J (1R,3R,4S,7E,11E,14R)-3,4-Dihydroxy-7,11,15(17)-cembratrien-16,14-olide Type: Cembrane diterpenoids. C20H30O4 Oil, [α]D25 = +7.3° (c = 0.7, CHCl3). Source: Soft coral Sarcophyton crassocaule (Taiwan Waters). Pharm: Cytotoxic (Doay cells, IC50 = 2.8 μg/mL; control Mitomycin, IC50 = 0.05 μg/mL; KB, IC50 > 20 μg/ mL; HeLa, IC50 > 20 μg/mL). Ref: H. C. Huang, et al, Chem. Biodivers., 2009, 6, 1232 OH 3

HO

O

O

568 Crassocolide K (1R,3S,4S,7S,11E,14S)-3,4-Epoxy-7-acetoxy-8(19),11,15(17)-cembratrien-16,14-olide Type: Cembrane diterpenoids. C20H30O5 Oil, [α]D25 = +26.3° (c = 0.8, CHCl3). Source: Soft coral Sarcophyton crassocaule (Taiwan Waters). Pharm: Cytotoxic (Doay cells, IC50 = 2.5 μg/mL; control Mitomycin, IC50 = 0.05 μg/mL; KB, IC50 > 20 μg/mL; HeLa, IC50 > 20 μg/mL). Ref: H. C. Huang, et al, Chem. Biodivers., 2009, 6, 1232 O O H

O

O

O

569 Crassocolide L Type: Cembrane diterpenoids. C22H30O7 Source: Soft coral Sarcophyton crassocaule (Kenting, Taiwan). Pharm: Cytotoxic (KB cells, IC50 = 12.2 μg/mL, control Mitomycin, IC50 = 0.08 μg/mL; HeLa, IC50 = 8.0 μg/mL, Mitomycin, IC50 = 0.06 μg/mL; Daey, IC50 = 4.1 μg/mL, Mitomycin, IC50 = 0.05 μg/mL;). Ref: H. C. Huang, et al, Chem. Biodivers., 2009, 6, 1232 HO

O O 3S

4S

O O O

O

186

3 Diterpenoids

570 Crassocolide M 3R,4R:7S,8S-Diepoxy-11,15(17)-cembradien-16,14-olide Type: Cembrane diterpenoids. C20H28O4 Oil, [α]D25 = +51.9° (c = 0.5, CHCl3). Source: Soft coral Sarcophyton crassocaule (Taiwan Waters). Pharm: Cytotoxic (Doay cells, IC50 = 1.1 μg/mL; control Mitomycin, IC50 = 0.05 μg/mL; KB, IC50 > 20 μg/mL; HeLa, IC50 > 20 μg/mL). Ref: H. -C. Huang, et al, Chem. Biodivers., 2009, 6, 1232 O 7S

4R

O

3R

1R

14S

8S

O

O

571 Crassocolide N Type: Cembrane diterpenoids. C20H26O4 Source: Soft coral Sinularia crassocaule (Kenting, Taiwan). Pharm: Cytotoxic (KB, IC50 = 4.7 μg/mL, control Mitomycin, IC50 = 0.08 μg/mL; HeLa, IC50 = 4.7 μg/mL, Mitomycin, IC50 = 0.06 μg/mL; Doay, IC50 = 2.8 μg/mL, Mitomycin, IC50 = 0.05 μg/mL). Ref: G. -H. Wang, et al, BoMCL, 2011, 21, 7201 O

O

O H O

572 Crassocolide O Type: Cembrane diterpenoids. C20H26O3 Source: Soft coral Sinularia crassocaule (Kenting, Taiwan). Pharm: Cytotoxic (KB, IC50 > 20 μg/mL, control Mitomycin, IC50 = 0.08 μg/mL; HeLa, IC50 > 20 μg/mL, Mitomycin, IC50 = 0.06 μg/mL; Doay, IC50 = 4.5 μg/mL, Mitomycin, IC50 = 0.05 μg/mL). Ref: G. -H. Wang, et al, BoMCL, 2011, 21, 7201 O

O

O H

3.13 Cembrane Diterpenoids

187

573 Crassocolide P Type: Cembrane diterpenoids. C22H30O4 Source: Soft corals Sinularia crassocaule (Kenting, Taiwan) and Lobophytum crassum. Pharm: Cytotoxic (KB, IC50 > 20 μg/mL, control Mitomycin, IC50 = 0.08 μg/mL; HeLa, IC50 = 10.8 μg/mL, Mitomycin, IC50 = 0.06 μg/mL; Doay, IC50 = 1.9 μg/mL, Mitomycin, IC50 = 0.05 μg/mL). Ref: M. Wanzola, et al, CPB, 2010, 58, 1203│G. -H. Wang, et al, BoMCL, 2011, 21, 7201 O

O

O

O H

574 Crassolide (1R,2S,3R,4S,5R,7E,9S,11E,14R)-3,4-Epoxy-5,9,14-triacetoxy-7,11,15(17)-cembratrien-16,2olide Type: Cembrane diterpenoids. C26H34O9 Amorph. solid, [α]D = −16° (c = 0.36, CHCl3). Source: Sponge Smenospongia sp., soft corals Lobophytum michaelae (Taiwan Waters) and Lobophytum crassum(Indonesia). Pharm: Cytotoxic (A549, ED50 = 0.39 μg/ mL; HT29, ED50 = 0.26 μg/mL; KB, ED50 = 0.85 μg/mL; P388, ED50 = 0.08 μg/mL); ichthyotoxin; inhibits cell cleavage of sea urchin eggs. Ref: B.Tursch, et al, Bull. Soc. Chim. Belg., 1978, 87, 75│C.Graillet, et al, Oceanis, 1991, 17, 229; CA, 116, 16939│S. -K. Wang, et al, JNP, 1992, 55, 1430 O O

O

O

O

O

O O O

575 Crassolide‡ Type: Cembrane diterpenoids. C20H28O3 Colorless oil, [α]D25 = +127.1° (c = 0.21, CHCl3). Source: Soft coral Sarcophyton crassocaule (Taiwan Waters). Pharm: Cytotoxic (A549, EC50 = 4.29 μg/mL, HT29, EC50 = 4.97 μg/mL, KB, EC50 = 8.35 μg/ mL, P388, EC50 = 0.14 μg/mL). Ref: C. -Y. Duh, et al, JNP, 2000, 63, 1634

188

3 Diterpenoids

1R 14R 12S

11S

H

O

O

O

576 Crassumol A Type: Cembrane diterpenoids. C20H34O3 Colorless oil, [α]D25 = −20° ( c = 0.1, CHCl3). Source: Soft coral Lobophytum crassum (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (A549, HT29 and P388, all ED50s > 50 μg/mL). Ref: S. -T. Lin, et al, Mar. Drugs, 2011, 9, 2705 OH OH OH

577 Crassumol B Type: Cembrane diterpenoids. C20H32O4 Colorless oil, [α]D25 = −40° ( c = 0.1, CHCl3). Source: Soft coral Lobophytum crassum (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (A549, HT29 and P388, all ED50s > 50 μg/mL). Ref: S. -T. Lin, et al, Mar. Drugs, 2011, 9, 2705 O HO O

OH

578 Crassumol C Sarcophytonin G Type: Cembrane diterpenoids. C22H34O4 Colorless oil, [α]D25 = −72° ( c = 0.1, CHCl3). Source: Soft corals Lobophytum crassum (Dongsha Atoll, South China Sea) and Sarcophyton sp. (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (A549, HT29 and P388, all ED50s > 50 μg/mL). Ref: S. -T. Lin, et al, Mar. Drugs, 2011, 9, 2705│S. -P. Chen, et al, Bull. Chem. Soc. Jpn., 2012, 85, 920

3.13 Cembrane Diterpenoids

189

O O

HO O

579 Crassumolide A (1R,3E,7E,10S,11E,14S)-10-Hydroxy-3,7,11,15(17)-cembratetraen-16,14-olide Type: Cembrane diterpenoids. C20H28O3 Gum, [α]D22 = −20° (c = 0.97, CHCl3). Source: Soft corals Lobophytum crassum and Lobophytum durum. Pharm: Anti-inflammatory (LPS-stimulated murine macrophage cells, inhibits up-regulation of pro-inflammatory iNOS and COX-2 proteins, IC50 < 10 μmol/L); cytotoxic (Ca9-22, IC50 = 3.2 μg/mL, control Doxorubicin, IC50 = 0.1 μg/mL; HepG2, IC50 > 5.0 μg/mL; Hep3B, IC50 > 5.0 μg/mL; MDA-MB-231, IC50 > 5.0 μg/mL; MCF7, IC50 > 5.0 μg/mL; A549, IC50 > 5.0 μg/mL). Ref: C. -H. Chao, et al, JNP, 2008, 71, 1819│S. -Y. Cheng, et al, Tetrahedron, 2008, 64, 9698

O

O

OH

580 Crassumolide C Type: Cembrane diterpenoids. C21H28O4 Gum, [α]D22 = +36° (c = 0.3, CHCl3). Source: Soft corals Lobophytum crassum and Lobophytum durum. Pharm: Anti-inflammatory (LPS-stimulated murine macrophage cells, inhibits up-regulation of proinflammatory iNOS and COX-2 proteins, IC50 < 10 μmol/L); cytotoxic (Ca9-22, IC50 = 1.7 μg/mL, control Doxorubicin, IC50 = 0.1 μg/mL; HepG2, IC50 > 5.0 μg/mL; Hep3B, IC50 > 5.0 μg/mL; MDA-MB-231, IC50 > 5.0 μg/mL; MCF7, IC50 > 5.0 μg/mL; A549, IC50 > 5.0 μg/mL). Ref: C. -H. Chao, et al, JNP, 2008, 71, 1819 O O O

2

O

190

3 Diterpenoids

581 Crassumolide G Type: Cembrane diterpenoids. C24H32O7 Source: Soft coral Lobophytum crassum (Dongsha Atoll, South China Sea). Pharm: Inhibits accumulation of iNOS (simulated macrophages). Ref: Y. -J. Tseng, et al, Bull. Chem. Soc. Jpn., 2011, 84, 1102 O

O

O H O O O

O

582 Crassumolide H Type: Cembrane diterpenoids. C22H30O6 Source: Soft coral Lobophytum crassum (Dongsha Atoll, South China Sea). Pharm: Inhibits accumulation of iNOS (simulated macrophages). Ref: Y. -J. Tseng, et al, Bull. Chem. Soc. Jpn., 2011, 84, 1102 OH O H O O O

O

583 Crassumolide I Type: Cembrane diterpenoids. C20H28O4 Source: Soft coral Lobophytum crassum (Dongsha Atoll, South China Sea). Pharm: Inhibits accumulation of iNOS (simulated macrophages). Ref: Y. -J. Tseng, et al, Bull. Chem. Soc. Jpn., 2011, 84, 1102 OH HO

H

O

O

584 Culobophylin A Type: Cembrane diterpenoids. C20H30O3 Colorless oil, [α]D25 = −50° (c = 0.1, CHCl3). Source: Soft coral Lobophytum crassum (Cultured, Pingtung county, Taiwan). Pharm: Cytotoxic (HL60, IC50 = 3 μg/mL, control Doxorubicin C, IC50 = 0.05 μg/mL; MDA-MB-231, IC50 = 16.8 μg/mL, control Doxorubicin C, IC50 = 6.3 μg/mL; DLD-1, IC50 = 4.6 μg/mL, Doxorubicin C, IC50 = 5.7 μg/mL; HCT116, IC50 = 16.3 μg/mL, Doxorubicin C, IC50 = 0.5 μg/mL); anti-inflammatory (immunoblot analysis assay,

3.13 Cembrane Diterpenoids

191

10 μmol/L, RAW264.7 macrophage cells, inhibition of LPS induced upregulation of iNOS and COX-2). Ref: N. -L. Lee, et al, Mar. Drugs, 2011, 9, 2526 OH H O H O

585 Culobophylin B Type: Cembrane diterpenoids. C20H32O3 Colorless oil, [α]D25 = −24° (c = 0.3, CHCl3). Source: Soft coral Lobophytum crassum (Cultured, Pingtung county, Taiwan). Pharm: Cytotoxic (HL60, IC50 = 6.8 μg/mL, control Doxorubicin C, IC50 = 0.05 μg/ mL; MDA-MB-231, IC50 > 20 μg/mL, control Doxorubicin C, IC50 = 6.3 μg/mL; DLD-1, IC50 = 16.2 μg/mL, Doxorubicin C, IC50 = 5.7 μg/mL; HCT116, IC50 = 16.7 μg/mL, Doxorubicin C, IC50 = 0.5 μg/mL); anti-inflammatory (immunoblot analysis assay, 10 μmol/L, RAW264.7 macrophage cells, inhibition of LPS induced upregulation of iNOS and COX-2). Ref: N. -L. Lee, et al, Mar. Drugs, 2011, 9, 2526 OH H O

O

586 Culobophylin C Type: Cembrane diterpenoids. C20H30O3 Colorless oil, [α]D25 = −83° (c = 0.3, CHCl3). Source: Soft coral Lobophytum crassum (Cultured, Pingtung county, Taiwan). Pharm: Cytotoxic (HL60, MDA-MB-231, DLD-1 and HCT116 cell lines, all IC50s > 20 = 0.05–6.35 μg/mL); μg/mL, control Doxorubicin C, IC50 anti-inflammatory (immunoblot analysis assay, 10 μmol/L, RAW264.7 macrophage cells, inhibition of LPS induced upregulation of iNOS and COX-2). Ref: N. -L. Lee, et al, Mar. Drugs, 2011, 9, 2526 O

OH H O

192

3 Diterpenoids

587 11-Dehydrosinulariolide Type: Cembrane diterpenoids. C20H28O4 Cryst. (Et2O), mp 120 °C, [α]D = +87° (EtOH). Source: Soft coral Sinularia flexibilis (southern coast, Taiwan). Pharm: Cytotoxic (HeLa, IC50 = 3.04 μg/mL, control Mitomycin C, IC50 = 0.08 μg/mL; Doay, IC50 = 2.46 μg/mL, Mitomycin C, IC50 = 0.06 μg/mL; Hep2, IC50 = 1.58 μg/mL, Mitomycin C, IC50 = 0.06 μg/mL; MCF7, IC50 = 3.14 μg/mL, Mitomycin C, IC50 = 0.09 μg/mL). Ref: M. Herin, et al, Bull. Soc. Chim. Belg., 1976, 85, 707│Y. S.Lin, et al, Tetrahedron, 2009, 65, 9157 O 6

H

O 12

O O

588 Denticulatolide Cembranolide C Type: Cembrane diterpenoids. C22H30O6 Cryst. (hexane/CH2Cl2), mp 129–130.5 °C, [α]D = +1.4° (c = 0.5, CHCl3). Source: Soft corals Lobophytum denticulatum, Sinularia mayi and Sarcophyton crassocaule. Pharm: Ichthyotoxin. Ref: T. Kusumi, et al, Tet. Lett., 1988, 29, 4731

O O

7S

O O

O O

589 Deoxosarcophine (2S,3E,7S,8S,11E)-2,16:7,8-Diepoxy-1(15),3,11-cembratriene Type: Cembrane diterpenoids. C20H30O2 Cryst. or oil, mp 72–73 °C, [α]D = +157° (c = 1, MeOH), [α]D = +135° (c = 0.93, CHCl3) ( +129°). Source: Soft corals Sarcophyton trocheliophorum, Sarcophyton glaucum Sarcophyton spp. and Lobophytum crassum. Pharm: Algicide; facilitator of neuromuscular transmission, calcium antagonist. Ref: Y. Kashman, et al, Tetrahedron, 1974, 30, 3615│B. Tursch, Pure Appl. Chem., 1976, 48, 1│J. Kobayashi, et al, Experientia, 1983, 39, 67│B. F. Bowden, et al, JNP, 1987, 50, 650

3.13 Cembrane Diterpenoids

193

O O

7 8

2

590 (1R,3R,4S,7E,11E)-(–)-14-Deoxycrassin Type: Cembrane diterpenoids. C20H30O3 Colorless oil, [α]D25 = −15° ( c = 1.0, CHCl3); Source: Soft coral Sinularia triangula (Taitung County, Taiwan). Pharm: Cytotoxic (CCRF-CEM, ED50 = 29.8 μmol/L, control Doxorubicin, ED50 = 0.57 μmol/L, DLD-1, ED50 = 32.2 μmol/L, Doxorubicin, ED50 = 0.25 μmol/L); anti-inflammatory (immunoblot analysis assay, 10 μmol/L, RAW264.7 macrophage cells, inhibition of LPS induced upregulation of COX-2 and iNOS, reduced COX-2 to (5.9 ± 1.0)%, reduced iNOS to (0.9 ± 0.7)%). Ref: J. -H. Su, et al, Mar. Drugs, 2011, 9, 944 OH

O O

591 (1S,3S,4R,7E,11E)-(+)-14-Deoxycrassin 4-Hydroxy-7,11,15(17)-cembratrien-16,3-olide Type: Cembrane diterpenoids. C20H30O3 Oil, [α]D26 = +29.6° ( c = 0.24, CHCl3). Source: Gorgonian Pseudoplexaura porosa. Pharm: Cytotoxic (HCT116, IC50 = 2 μg/mL; SK5-MEL, IC50 = 0.5 μg/mL; A498, IC50 = 0.2 μg/mL). Ref: A. D. Rodríguez, et al, Experientia, 1993, 49, 179 OH

O O

H

592 (2R,3E,7S,8S,11E)-2,16:7,8-Diepoxy-1(15),3,11-cembratriene Type: Cembrane diterpenoids. C20H30O2 Cryst., mp 52–56 °C, [α]D = −64° (c = 0.6, CHCl3). Source: Soft corals Lobophytum pauciflorum and Sarcophyton sp. Pharm: Ichthyotoxin. Ref: B. F. Bowden, et al, JNP, 1987, 50, 650

194

3 Diterpenoids

O O

593 (1R,7S,8S,11S,12S,13R)-3,6:11,12-Diepoxy-7,13-diacetoxy-8-hydroxy-18-oxo3,5,15-cembratrien-20,10-olide Type: Cembrane diterpenoids. C24H28O10 Cryst. (EtOAc/hexane), mp 254–258 °C, [α]D25 = −13° (c = 1,CDCl3). Source: Gorgonian Lophogorgia violacea (Brazil). Pharm: Antifeedant (fish). Ref: R. de A. Epifanio, et al, J. Braz. Chem. Soc., 2000, 11, 584 O O

O

1

OH O O

14 13

O

O

O O

594 Dihydrosinuflexolide Type: Cembrane diterpenoids. C20H34O5 Cryst., mp 165–167 °C, [α]D25 = −3.8° (c = 0.066, MeOH). Source: Soft coral Sinularia flexibilis (Taiwan Waters). Pharm: Cytotoxic (A549, ED50 = 16.8 μg/mL; HT29, ED50 = 32.4 μg/mL; KB, ED50 > 50 μg/ mL; P388, ED50 = 3.86 μg/mL). Ref: C. -Y. Duh, et al, JNP, 1998, 61,844 O

HO O

H

OH

OH

595 Dihydrosinularin Dihydroflexibilide Type: Cembrane diterpenoids. C20H32O4 White powder; mp 116– 118 °C, [α]D25 = −42° ( c = 0.3, CHCl3); Cryst. (toluene/hexane), mp 108–109 °C, [α]D21 = −44° ( c = 1, CHCl3); Source: Soft corals Sinularia triangula (Taitung County, Taiwan) and Sinularia flexibilis, prosobranch Planaxis sulcatus. Pharm: Anti-inflammatory (immunoblot analysis assay, 10 μmol/L, RAW264.7 macrophage cells, inhibition of LPS induced upregulation of COX-2 and iNOS, reduced COX-2 to (24.9 ± 7.4)%, reduced iNOS to (5.1 ± 1.6)%); cytotoxic. Ref: A. J. Weinheimer,et al,

3.13 Cembrane Diterpenoids

195

Tetrahedron Lett. 1977, 34, 2923│R. Sanduja, et al, JNP, 1986, 49, 718│J. -H. Su, et al, Mar. Drugs, 2011, 9, 944 OH

O O

H

O

596 17-(N,N-Dimethyl)-amino-3,7,11-cembratrien-16,2-olid-19-oic acid Type: Cembrane diterpenoids. C22H33NO4 White gum, [α]D = +13.1° (c = 0.25, CHCl3). Source: Soft coral Lobophytum sp. (Philippines). Pharm: Anti-HIV-1 (cell-based assay,inhibits cytopathic effect of in vitro HIV-1 infection). Ref: M. A. Rashid, et al, JNP, 2000, 63, 531 O

O 7

16

3

COOH

1

N

15 17

11

597 17-Dimethylaminolobohedleolide Type: Cembrane diterpenoids. C21H31NO4 Source: Soft coral Lobophytum sp. (aqueous extract). Pharm: Anti-HIV (cell-based in vitro assay, EC50 = 3.3 μg/mL, IC50 = 10.2 μg/mL, with maximum cellular protection 55%–70%). Ref: M. A. Rashid, et al, JNP, 2000, 63, 531 O O HO

O

2

N

598 Durumhemiketalolide A Type: Cembrane diterpenoids. C20H28O5 Oil, [α]D25 = +140° (c = 0.1, CHCl3). Source: Soft coral Lobophytum durum. Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L: inhibits up-regulation of proinflammatory iNOS to 11.0% and COX-2 to 66.7% compare with control LPSstimulated cells alone; protein β-actin is not changed). Ref: S. -Y. Cheng, et al, JNP, 2009, 72, 152

196

3 Diterpenoids

HO

18

O

O

4

O OH

599 Durumhemiketalolide B Type: Cembrane diterpenoids. C22H30O6 Oil, [α]D25 = +40° (c = 0.3, CHCl3). Source: Soft coral Lobophytum durum. Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L: inhibits up-regulation of proinflammatory iNOS to 6.4%compare with control LPS-stimulated cells alone; but doesn’t inhibit COX-2 protein expression; protein β-actin is not changed). Ref: S. Y. Cheng, et al, JNP, 2009, 72, 152 O O

18

O

O

4

O OH

600 Durumhemiketalolide C Type: Cembrane diterpenoids. C22H30O6 Oil, [α]D25 = +130° (c = 0.1, CHCl3). Source: Soft coral Lobophytum durum. Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L: inhibits up-regulation of pro-inflammatory iNOS to 0.0% and COX-2 to 34.7% compare with control LPS-stimulated cells alone; protein β-actin is not changed). Ref: S. Y. Cheng, et al, JNP, 2009, 72, 152 O O

18

O

O

4

O OH

601 Durumolide A Type: Cembrane diterpenoids. C22H30O7 Oil, [α]D24 = +93° (c = 0.2, CHCl3). Source: Soft corals Lobophytum durum and Lobophytum crassum. Pharm: Antiinflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L,

3.13 Cembrane Diterpenoids

197

inhibits up-regulation of pro-inflammatory iNOS to 34.7% and COX-2 to 62.5% compare with control LPS-stimulated cells alone, IC50 < 10 μmol/L; MMOA: inducible NOS and COX-2 inhibition; 10 μmol/L, mouse keeping protein β-actin is not changed); antibacterial (Salmonella enteritidis, 200 μg/disk, significant; control Ampicillin, 250 μg/disk, significant). Ref: S. -Y. Cheng, et al, Tetrahedron, 2008, 64, 9698│C. -H. Chao, et al, JNP, 2008, 71, 1819 O O

HO

O

H

HO

O

O

602 Durumolide B Type: Cembrane diterpenoids. C22H30O5 Oil, [α]D24 = +41.5° (c = 0.4, CHCl3). Source: Soft corals Lobophytum durum and Lobophytum crassum. Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L, doesn’t inhibit up-regulation of pro-inflammatory COX-2, but inhibis iNOS to 0.0%, compare with control LPS-stimulated cells alone; MMOA: inducible NOS and COX-2 inhibition; 10 μmol/L, mouse keeping protein β-actin is not changed); antibacterial (Salmonella enteritidis, 100 μg/disk, significant; control Ampicillin, 250 μg/disk, significant). Ref: S. -Y. Cheng, et al, Tetrahedron, 2008, 64, 9698│C. -H. Chao, et al, JNP, 2008, 71, 1819 O O HO O

O

603 Durumolide C Presinularolide B Type: Cembrane diterpenoids. C20H28O4 Oil, [α]D20 = +33.8° (c = 0.54, CHCl3), [α]D24 = +15.4° (c = 1, CHCl3). Source: Soft corals Lobophytum durum and Lobophytum crassum. Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L, inhibits up-regulation of pro-inflammatory iNOS to 0.0% and COX-2 to 42.5% compare with control LPSstimulated cells alone, IC50 < 10 μmol/L; MMOA: inducible NOS and COX-2 inhibition; 10 μmol/L, mouse keeping protein β-actin is not changed); antibacterial (Salmonella enteritidis, 100 μg/disk, significant; control Ampicillin, 250 μg/disk,

198

3 Diterpenoids

significant). Ref: S. -Y. Cheng,et al, Tetrahedron, 2008, 64, 9698│C. -H. Chao, et al, JNP, 2008, 71, 1819│W. Zhang, et al, JNP, 2008, 71, 961 OH

HO O

O

604 Durumolide D Type: Cembrane diterpenoids. C22H30O6 Oil, [α]D24 = +10.2° (c = 1.8, CHCl3). Source: Soft coral Lobophytum durum. Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L, doesn’t inhibit up-regulation of pro-inflammatory COX-2, but inhibis iNOS to 0.5%, compare with control LPSstimulated cells alone; 10 μmol/L, mouse keeping protein β-actin is not changed); antibacterial (Salmonella enteritidis, 250 μmg/disk, significant; control Ampicillin, 250 μg/disk, significant). Ref: S. -Y. Cheng, et al, Tetrahedron, 2008, 64, 9698 O O OH O O

O

605 Durumolide E 3,4-Epoxy-13-hydroxy-18-oxo-7,11,15(17)-cembratrien-16,14-olide Type: Cembrane diterpenoids. C20H26O5 Oil, [α]D24 = +32° (c = 0.3, CHCl3). Source: Soft coral Lobophytum durum. Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L, doesn’t inhibit up-regulation of pro-inflammatory COX-2, but inhibis iNOS to 0.1%, compare with control LPS-stimulated cells alone; 10 μmol/L, mouse keeping protein β-actin is not changed); antibacterial (Salmonella enteritidis, 200 μg/disk, significant; control Ampicillin, 250 μg/disk, significant). Ref: S. -Y. Cheng, et al, Tetrahedron, 2008, 64, 9698

3.13 Cembrane Diterpenoids

199

H

O

O 3R 4S

HO 13R

O

O

606 Durumolide P Type: Cembrane diterpenoids. C21H32O5 Colorless oil, [α]D25 = −121° ( c = 0.1, CHCl3). Source: Soft coral Lobophytum durum (Dongsha Atoll, Taiwain). Pharm: Cytotoxic (P388, ED50 = 3.8 μg/mL). Ref: S. -Y. Cheng, et al, Mar. Drugs, 2011, 9, 1307 HO O H O O

O

607 Durumolide Q Type: Cembrane diterpenoids. C21H32O5 Colorless oil, [α]D25 = −99° ( c = 0.2, CHCl3). Source: Soft coral Lobophytum durum (Dongsha Atoll, Taiwain). Pharm: Antiviral (hmn cytomegalovirus HCMV, IC50 = 5.2 μg/mL). Ref: S. -Y. Cheng, et al, Mar. Drugs, 2011, 9, 1307 O H O

HO O

O

608 Ehrenbergol A Type: Cembrane diterpenoids. C21H32O4 White amorphous powder, [α]D25 = −184° (c = 0.1, CHCl3). Source: Soft coral Sarcophyton ehrenbergi (Taitung County, Taiwan). Pharm: Cytotoxic (A549, ED50 > 50 μg/mL; HT29, ED50 > 50 μg/mL; P388, ED50 = 7.4 μg/mL; HEL, ED50 > 50 μg/mL); antiviral (hmn cytomegalovirus (HCMV), hmn embryonic lung (HEL) cell line, ED50 = 46 μg/mL). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 1433

200

3 Diterpenoids

OH

O

O O

609 Ehrenbergol B Type: Cembrane diterpenoids. C22H36O4 White amorphous powder, [α]D25 = −84° (c = 0.1, CHCl3). Source: Soft coral Sarcophyton ehrenbergi (Taitung County, Taiwan). Pharm: Cytotoxic (A549, ED50 = 10.2 μg/mL; HT29, ED50 > 50 μg/mL; P388, ED50 = 4.7 μg/mL; HEL, ED50 > 50 μg/mL); antiviral (hmn cytomegalovirus (HCMV), hmn embryonic lung (HEL) cell line, ED50 = 5.0 μg/mL). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 1433 O O

O

OH

610 Ehrenbergol C Type: Cembrane diterpenoids. C21H30O6 Source: Soft coral Sarcophyton ehrenbergi (Sansiantai, Taitung county, Taiwan). Pharm: Cytotoxic (P388, mild). Ref: S. -K. Wang, et al, Mar. Drugs, 2013, 11, 4318 H

OH

O HO

O

O O

611 Ehrenberoxide A Type: Cembrane diterpenoids. C22H34O4 Source: Soft coral Sarcophyton ehrenbergi (Dongsha Atoll, South China Sea). Pharm: Antiviral (mild). Ref: S. -Y. Cheng, et al, JNP, 2010, 73, 197

3.13 Cembrane Diterpenoids

201

O

O

O O

612 Ehrenberoxide B Type: Cembrane diterpenoids. C20H34O3 Source: Soft coral Sarcophyton ehrenbergi (Dongsha Atoll, South China Sea). Pharm: Antiviral (mild). Ref: S. -Y. Cheng, et al, JNP, 2010, 73, 197

O HO HO

613 Ehrenberoxide C Type: Cembrane diterpenoids. C20H34O3 Source: Soft coral Sarcophyton ehrenbergi (Dongsha Atoll, South China Sea). Pharm: Antiviral (mild). Ref: S. -Y. Cheng, et al, JNP, 2010, 73, 197

O

HO

OH

614 Emblide Type: Cembrane diterpenoids. C23H32O6 Cryst. (MeOH), mp 119–120 °C, [α]D25 = +92° (c = 1.3, CCl4). Source: Soft coral Sarcophyton glaucum. Pharm: Cytotoxic (KB, IC50 = 5.0 μg/mL). Ref: J. A. Toth, et al, Tetrahedron, 1980, 36, 1307 1

3Z

O O

O

7

O

11 8R

O O

202

3 Diterpenoids

615 4,10-Epoxy-2,7,11-cembratriene Type: Cembrane diterpenoids. C20H32O Oil. Source: Soft coral Sarcophyton sp. (Thailand). Pharm: Antifoulant. Ref: U. Anthoni, et al, Tet. Lett., 1991, 32, 2825

O

616 11,12-Epoxy-1,3,7-cembratrien-15-ol Type: Cembrane diterpenoids. C20H32O2 Colourless oil, [α]D25 = −8.6° (c = 0.17, CHCl3). Source: Soft corals Sinularia sp. (Bowden Reef, Great Barrier Reef, Australia) and Sinularia gibberosa. Pharm: Cytotoxic (SF268, GI50 = 6.8 μmol/L, MCF7, GI50 = 12 μmol/L, H460, GI50 = 18.5 μmol/L). Ref: C. -Y. Duh, et al, JNP, 1996, 59, 595│A. D. Wright, et al, Mar. Drugs, 2012, 10, 1619

OH O

617 (1S,3R,4R,6E,8R,12S,13R,14R)-3,4-Epoxy-8,13-diacetoxy-6,15(17)-cembradien16,14-olide Type: Cembrane diterpenoids. C24H34O7 Semisolid, [α]D25 = −5.2° (c = 5.6, CHCl3). Source: Annelida Eunicea mammosa (Caribbean Sea). Pharm: Cytotoxic (in vitro). Ref: A. D. Rodríguez, et al, Can. J. Chem., 1995, 73, 643│A. D. Rodríguez, et al, JNP, 1995, 58, 1209 O

O O

O O O

O

618 (1S,3R,4R,6E,8S,12S,13R,14R)-3,4-Epoxy-8,13-diacetoxy-6,15(17)-cembradien16,14-olide Type: Cembrane diterpenoids. C24H34O7 Semisolid, [α]D25 = +9.3° (c = 2.7, CHCl3). Source: Annelida Eunicea mammosa (Caribbean Sea). Pharm: Cytotoxic (in vitro).

3.13 Cembrane Diterpenoids

203

Ref: A. D. Rodríguez, et al, Can. J. Chem., 1995, 73, 643│A. D. Rodríguez, et al, JNP, 1995, 58, 1209 O

O O

O O O

O

619 11,12-Epoxypukalide Type: Cembrane diterpenoids. C21H24O7 Cryst. (CHCl3/pentane), [α]D = −5.33° (c = 0.6, MeOH). Source: Gorgonian Leptogorgia setacea. Pharm: Ichthyodeterrent activity. Ref: M. B. Ksebati, et al, JNP, 1984, 47, 1009 O O

O

7S

1R

O O

8R

O O

620 (+)-11S,12S-Epoxysarcophytol A Type: Cembrane diterpenoids. C20H32O2 Needles (MeCN), mp 75–76 °C, [α]D20 = +218° (nat., c = 0.35, CHCl3), [α]D = +229° (syn., c = 0.95, CHCl3). Source: Soft coral Lobophytum sp. (Australia). Pharm: Toxic (brine shrimp). Ref: B. F. Bowden, et al, Aust. J. Chem., 1983, 36, 2289│J. Lan, et al, Tet. Lett., 2000, 41, 2181

O H

OH

621 (+)-12-Ethoxycarbonyl-11Z-sarcophine Type: Cembrane diterpenoids. C22H30O5 White amorphous powder, [α]D25 = +77° (c = 0.2, CHCl3). Source: Soft coral Sarcophyton ehrenbergi (Taitung County, Taiwan). Pharm: Cytotoxic (A549, ED50 = 24.8 μg/mL; HT29, ED50 > 50 μg/mL; P388, ED50 = 5.8 μg/mL; HEL, ED50 > 50 μg/mL); antiviral (hmn cytomegalovirus (HCMV), hmn embryonic lung (HEL) cell line, ED50 = 60 μg/mL). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 1433

204

3 Diterpenoids

O

O

H O

O O

622 Eunicenolide Type: Cembrane diterpenoids. C20H30O6 Oil, [α]D25 = +13.7° (c = 2.0, CHCl3). Source: Annelida Eunicea succinea (Mona I., Puerto Rico). Pharm: Cytotoxic (NCI in vitro primary disease-oriented antitumor screen, moderate cytotoxicity, 10-5 mol/L, against only one ovarian (IGROV1), one nonsmall cell lung (NCI-H522), and two leukemia (CCRF-CEM and RPMI8226) cancer cell lines). Ref: A. D. Rodriguez, et al, JNP, 1998, 61, 40 OH 7S

O

OH

O 8R

O

O

623 Eunicin Type: Cembrane diterpenoids. C20H30O4 Cryst., mp 154–155.5 °C, [α]D29 = −95° (c = 2.0, EtOH). Source: Annelida Eunicea mammosa (Bimini Is., Bahamas), Eunicea succinea, gorgonian Pseudoplexaura sp. Pharm: Antibacterial; cytotoxic. Ref: A. J. Weinheimer, et al, Chem. Commun., 1968, 385│Y. Gopichand, et al, JNP, 1984, 47, 607│R. T. Gampe, Jr., et al, JACS, 1984, 106, 1823│A. D. Rodriguez, et al, JNP, 1993, 56, 564 OH

O O

O

624 Eupalmerin acetate Type: Cembrane diterpenoids. C22H32O5 Source: Annelida Eunicea palmari, Eunicea succinea and Eunicea mammosa. Pharm: Algicide. Ref: L.A.Fontán, et al, JOC, 1990, 55, 4956│A. D. Rodriguez, et al, JNP, 1993, 56, 564

3.13 Cembrane Diterpenoids

205

O O

OH O

O

625 12,13-bisepi-Eupalmerin epoxide Type: Cembrane diterpenoids. C20H30O5 Oil, [α]D25 = −13.2° (c = 4.4, CHCl3). Source: Annelida Eunicea succinea (Mona I., Puerto Rico). Pharm: Cytotoxic (NCI in vitro primary disease-oriented antitumor screen, 10−6 mol/L, responses at LC50 level from nearly all breast cancer cell lines and from several of colon cancer cell lines). Ref: A. D. Rodriguez, et al, JNP, 1998, 61, 40 O

H 7S

O

HO 8R 13 12

O

O

626 12-epi-Eupalmerone Sarcophyocrassolide B; Sarcocrassolide B Type: Cembrane diterpenoids. C20H28O4 Cryst., mp 92 °C, mp 96–97 °C, [α]D25 = −25.9° (c = 1, CHCl3). Source: Soft coral Sarcophyton crassocaule, Annelida Eunicea pinta. Pharm: Cytotoxic (NCI-H322M, IC50 = 0.9 μg/mL; TK10, IC50 = 0.13 μg/mL). Ref: Y. -P.Shi, et al, JNP, 2002, 65, 1232│Y. -P.Shi, et al, JNP, 2002, 65, 1232│X. H. Xu, et al, Chin. J. Chem., 2003, 21, 1506│X. H. Xu, et al, Gaodeng Xuexiao Huaxue Xuebao, 2003, 24, 1023 O O H 13

O

O

627 Flabellatene A Type: Cembrane diterpenoids. C20H30O4 Yellow oil, [α]D = −12.7° (c = 0.3, CHCl3). Source: Sponge Lissodendoryx flabellate (Antarctic). Pharm: Cytotoxic (mus neuroblastoma cells N18-T62, 0.16 μmol/L); antiproliferative (hmn DU145 and MCF7 cells). Ref: A. Fontana, et al, Tetrahedron, 1999, 55, 1143

206

3 Diterpenoids

HO

O O OH

628 Flabellatene B 3,4-Epoxy-13,19-dihydroxy-1,7-cembradiene-9,14-dione Type: Cembrane diterpenoids. C20H30O5 Yellow oil, [α]D = +5.2° (c = 0.2, CHCl3). Source: Sponge Lissodendoryx flabellate (Antarctic). Pharm: Cytotoxic (similar with Flabellatene A). Ref: A. Fontana, et al, Tetrahedron, 1999, 55, 1143 HO O O

O

HO

629 Flaccidoxide acetate Type: Cembrane diterpenoids. C24H36O5 Colorless oil, [α]D21 = +157.8° (c = 0.78, CHCl3). Source: Soft coral Cladiella kashmani (Mozambique). Pharm: Toxic (brine shrimp Artemia salina). Ref: C. A. Gray, et al, JNP, 2000, 63, 1551

O

O

1

11S

O

12R

O O

630 Flexibilisolide C Type: Cembrane diterpenoids. C20H26O5 Source: Soft coral Sinularia flexibilis (Dongsha Atoll, South China Sea). Pharm: Cytotoxic; reducer of accumulation of iNOS and COX2 proinflammatory proteins. Ref: H. -J. Shih, et al, Tetrahedron, 2012, 68, 244 O

O

O

H

O O

3.13 Cembrane Diterpenoids

207

631 Flexilarin B Type: Cembrane diterpenoids. C21H32O4 Oil, [α]D = +79° (c = 0.2, CH2Cl2). Source: Soft coral Sinularia flexibilis (southern coast, Taiwan). Pharm: Cytotoxic (HeLa, IC50 > 20 μg/mL, control Mitomycin C, IC50 = 0.08 μg/mL; Doay, IC50 = 19.7 μg/mL, Mitomycin C, IC50 = 0.06 μg/mL; Hep2, IC50 = 12.2 μg/mL, Mitomycin C, IC50 = 0.06 μg/mL; MCF7, IC50 > 20 μg/mL, Mitomycin C, IC50 = 0.09 μg/mL). Ref: Y.S.Lin, et al, Tetrahedron, 2009, 65, 9157 O

O

O

H

H O

632 Flexilarin D (1R,3S,4S,6E,8S,11R,12R)-3,4-Epoxy-8-hydroperoxide–11-oxo-6,15(17)-cembradien16,12-olide Type: Cembrane diterpenoids. C20H28O6 Oil, [α]D = +32° (c = 0.2, CH2Cl2). Source: Soft coral Sinularia flexibilis (southern coast, Taiwan). Pharm: Cytotoxic (HeLa, IC50 = 0.41 μg/mL, control Mitomycin C, IC50 = 0.08 μg/mL; Doay, IC50 = 1.24 μg/mL, Mitomycin C, IC50 = 0.06 μg/mL; Hep2, IC50 = 0.07 μg/ mL, Mitomycin C, IC50 = 0.06 μg/mL; MCF7, IC50 = 1.24 μg/mL, Mitomycin C, IC50 = 0.09 μg/mL). Ref: Y.S.Lin, et al, Tetrahedron, 2009, 65, 9157

4S 8S

O

H

O 3S

1R

OH

O 11

O

O

12R

633 Flexilarin G (1R,3S,4S,6E,8S,11R,12R)-3,4-Epoxy-8,11-dihydroxy-6,15(17)-cembradien-16,12-olide Type: Cembrane diterpenoids. C20H30O5 Oil, [α]D = +33° (c = 0.2, CH2Cl2). Source: Soft coral Sinularia flexibilis (southern coast, Taiwan). Pharm: Cytotoxic (HeLa, IC50 = 8.23 μg/mL, control Mitomycin C, IC50 = 0.08 μg/mL; Doay, IC50 = 10.5 μg/mL, Mitomycin C, IC50 = 0.06 μg/mL; Hep2, IC50 = 6.22 μg/mL, Mitomycin C, IC50 = 0.06 μg/mL; MCF7, IC50 = 10.8 μg/mL, Mitomycin C, IC50 = 0.09 μg/mL). Ref: Y.S.Lin, et al, Tetrahedron, 2009, 65, 9157

208

3 Diterpenoids

O

4S 8S

H

OH

1R

3S

OH 11R

O

O

12R

634 Granosolide A Type: Cembrane diterpenoids. C22H32O6 Powder, mp 187–189 °C, [α]D25 = −8.1° (c = 0.7, CHCl3). Source: Soft coral Sinularia granosa. Pharm: Cytotoxic (HeLa, Hep2, Doay, MCF7, all ED50s > 20 μg/mL). Ref: Y. Lu, et al, JNP, 2008, 71, 1754 O O

O O 11

O OH

635 Granosolide B Type: Cembrane diterpenoids. C24H34O7 Powder, mp 175–177 °C, [α]D25 = −38° (c = 0.4, CHCl3). Source: Soft coral Sinularia granosa. Pharm: Cytotoxic (HeLa, Hep2, Doay, MCF7, all ED50s > 20 μg/mL). Ref: Y. Lu, et al, JNP, 2008, 71, 1754 O O

O O O

O O

636 (3E,7S,11Z)-7-Hydroxy-3,11,15-cembratrien-20,8-olide Type: Cembrane diterpenoids. C20H30O3 Glass, [α]D24 = +3° (c = 1). Source: Annelida Eunicea tourneforti. Pharm: Antifungal (Inhibits RS321, IC12 > 3000 μg/mL). Ref: M. Govindan, et al, JNP, 1995, 58, 1174

HO

O

O

3.13 Cembrane Diterpenoids

209

637 Isosarcophinone Type: Cembrane diterpenoids. C20H28O3 Source: Soft coral Sarcophyton molle. Pharm: Cytotoxic (2.5 μg/mL: EAC, InRt = 70%, S180 mouse sarcoma cell, InRt = 53.9%). Ref: J. Y. Su, et al, Gaodeng Xuexiao Huaxue Xuebao, 2001, 22, 1515│Renlin Zou, et al, 1989, Corals and their Medical useage, Science Press, Beijing. O 2

O

O

638 Isosarcophytoxide Type: Cembrane diterpenoids. C20H30O2 Cryst. (petrol), mp 67–69 °C, [α]D = −166.1° (c = 0.15, CHCl3). Source: Soft coral Sarcophyton sp. Pharm: Antimycobacterial (weak activity); Calcium antagonist. Ref: B. F. Bowden, et al, Aust. J. Chem., 1979, 32, 653

O

O

639 Jeunicin (1S,3R,4S,7E,12R,13R,14R)-4,13-Epoxy-3-hydroxy-7,15(17)-cembradien-16,14-olide Type: Cembrane diterpenoids. C20H30O4 Cryst., mp 139–141 °C, [α]D27 = +12.8° (c = 0.75, CHCl3). Source: Annelida Eunicea mammosa (Jamaica) and Eunicea succinea, prosobranch Planaxis sulcatus. Pharm: Cytotoxic. Ref: D. Van der Helm, et al, Acta Cryst. B, 1976, 32, 1558│A. J. Westheimer, et al, Acta Cryst. B, 1982, 38, 580│Y. Gopichand, et al, JNP, 1984, 47, 607│R.Sanduja, et al, J. Het. Chem., 1986, 23, 529 OH

O

4S 14R

H

O O

210

3 Diterpenoids

640 13αH,14βH-Jeunicin Type: Cembrane diterpenoids. C20H30O4 Cryst., mp 147–147.5 °C, Source: Annelida Eunicea mammosa. Pharm: Cytotoxic. Ref: A.J.Westheimer, et al, Acta Cryst. B, 1982, 38, 580 OH

O H

O O

641 Kericembrenolide A Type: Cembrane diterpenoids. C22H30O4 Oil, [α]D22 = −88° (CHCl3); [α]D25 = −102.3° (c = 0.13, CHCl3). Source: Stolonifer Clavularia koellikeri (Okinawa). Pharm: Cytotoxic (B16 cells, IC50 = 3.8 μg/mL). Ref: M. Kobayashi, et al, CPB, 1986, 34, 2306│M. Iwashima, et al, JNP, 2000, 63, 1647 O O

18

H

H

17

O

O

6S 3

19

15 1 14

16

H

10

20

642 Kericembrenolide B Type: Cembrane diterpenoids. C22H30O4 Oil, [α]D22 = +97° (CHCl3). Source: Stolonifer Clavularia koellikeri (Okinawa). Pharm: Cytotoxic (B16 cells, IC50 = 2.5 μg/mL). Ref: M. Kobayashi, et al, CPB, 1986, 34, 2306 18

H O

6

O

10

3

19

O

17

O 15

1 14

H

16

20

643 Kericembrenolide C Type: Cembrane diterpenoids. C24H32O6 Oil, [α]D22 = −56° (CHCl3). Source: Stolonifer Clavularia koellikeri (Okinawa). Pharm: Cytotoxic (B16 cells, IC50 = 1.3 μg/mL). Ref: M. Kobayashi, et al, CPB, 1986, 34, 2306

3.13 Cembrane Diterpenoids

211

O O

18

H

O

17

O

6 15

3

19

1 14

16

H

10

O

20

O

644 Kericembrenolide D Type: Cembrane diterpenoids. C22H30O5 Oil, [α]D22 = −71° (CHCl3). Source: Stolonifer Clavularia koellikeri (Okinawa). Pharm: Cytotoxic (B16 cells, IC50 = 1.2 μg/mL). Ref: M. Kobayashi, et al, CPB, 1986, 34, 2306 O O

18

H

O

17

O

6 15

3

19

1 14

16

H

10

OH

20

645 Kericembrenolide E (1S,2S,3E,6S,7E,11E,14S)-6,14-Dihydroxy-3,7,11,15(17)-cembratetraen-16,2-olide Type: Cembrane diterpenoids. C20H28O4 [α]D21 = −53° (CHCl3). Source: Stolonifer Clavularia koellikeri (Okinawa). Pharm: Cytotoxic (B16 cells, IC50 = 1.8 μg/mL). Ref: M. Kobayashi, et al, CPB, 1986, 34, 2306 OH

18

H

O

17

O

6 15

3

19

1 14

10

20

H

16

OH

646 Knightal 7,8-Epoxy-3,11,15-cembratrien-18-al Type: Cembrane diterpenoids. C20H30O2 Oil, [α]D25 = +7° (c = 2.9, CHCl3). Source: Annelida Eunicea knighti (Santa Marta Bay, Caribbean Sea, Colombia). Pharm: Active in an anti-quorum-sensing bioassay. Ref: E. Tello,et al, JNP, 2009, 72, 1595

212

3 Diterpenoids

H

O

H O

647 Knightol Type: Cembrane diterpenoids. C20H32O2 Oil, [α]D25 = −32° (c = 2.5, CHCl3). Source: Annelida Eunicea knighti (Santa Marta Bay, Caribbean Sea, Colombia). Pharm: Active in an anti-quorum-sensing bioassay; antibacterial (marine gram + bacteria, MID = 2–8 μg/disk). Ref: E. Tello,et al, JNP, 2009, 72, 1595 OH H O

648 Lobocrassin A Type: Cembrane diterpenoids. C20H29ClO4 Colorless oil, [α]D25 = +28° (c = 0.63, CHCl3). Source: Soft coral Lobophytum crassum (Northeast Taiwan). Pharm: Cytotoxic (K562, IC50 = 15.39 μg/mL, control Doxorubicin, IC50 = 0.24 μg/mL; CCRF-CEM, IC50 = 5.33 μg/mL, Doxorubicin, IC50 = 0.05 μg/mL; Molt4, IC50 = 11.86 μg/mL, Doxorubicin, IC50 = 0.07 μg/mL; HepG2, IC50 = 32.16 μg/mL, Doxorubicin, IC50 = 0.71 μg/mL; Huh7, IC50 = 26.13 μg/mL, Doxorubicin, IC50 = 0.46 μg/mL); anti-inflammatory (Hmn neutrophils, inhibits generation of superoxide anion, 10 μg/mL, InRt = (2.8 ± 1.9)%, control DPI, IC50 = (0.8 ± 0.2)μg/mL); elastase release inhibitor (hmn neutrophils, response to formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB), 10 μg/mL, InRt = (0.9 ± 2.5)%, control Elastatinal, IC50 = (30.8 ± 5.7)μg/mL). Ref: C. -Y. Kao, et al, Mar. Drugs, 2011, 9, 1319 O

Cl H OH O

O

3.13 Cembrane Diterpenoids

213

649 Lobocrassin B Type: Cembrane diterpenoids. C20H30O3 Colorless oil, [α]D25 = −40° (c = 0.07, CHCl3). Source: Soft coral Lobophytum crassum (Northeast Taiwan). Pharm: Cytotoxic (K562, IC50 = 2.97 μg/mL, control Doxorubicin, IC50 = 0.24 μg/mL; CCRFCEM, IC50 = 0.48 μg/mL, Doxorubicin, IC50 = 0.05 μg/mL; Molt4, IC50 = 0.34 μg/mL, Doxorubicin, IC50 = 0.07 μg/mL; HepG2, IC50 = 3.44 μg/mL, Doxorubicin, IC50 = 0.71 μg/mL; Huh7, IC50 = 8.17 μg/mL, Doxorubicin, IC50 = 0.46 μg/mL); anti-inflammatory (hmn neutrophils, inhibits generation of superoxide anion, IC50 = (4.8 ± 0.7)μg/ mL, control DPI, IC50 = (0.8 ± 0.2)μg/mL); elastase release inhibitor (hmn neutrophils, response to formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB), IC50 = (4.9 ± 0.4) μg/mL, control Elastatinal, IC50 = (30.8 ± 5.7)μg/mL). Ref: C. -Y. Kao, et al, Mar. Drugs, 2011, 9, 1319 OH O H H

O

14

650 Lobocrassin C Type: Cembrane diterpenoids. C20H32O2 Colorless oil, [α]D25 = +17° (c = 0.37, CHCl3). Source: Soft coral Lobophytum crassum (Northeast Taiwan). Pharm: Cytotoxic (K562, IC50 > 40 μg/mL, control Doxorubicin, IC50 = 0.24 μg/mL; CCRF-CEM, IC50 = 11.55 μg/mL, Doxorubicin, IC50 = 0.05 μg/mL; Molt4, IC50 = 9.51 μg/mL, Doxorubicin, IC50 = 0.07 μg/mL; HepG2, IC50 > 40 μg/mL, Doxorubicin, IC50 = 0.71 μg/mL; Huh7, IC50 = 39.77 μg/mL, Doxorubicin, IC50 = 0.46 μg/mL); anti-inflammatory (Hmn neutrophils, inhibits generation of superoxide anion, 10 μg/mL, InRt = (1.4 ± 2.4)%, control DPI, IC50 = (0.8 ± 0.2)μg/mL); elastase release inhibitor (hmn neutrophils, response to formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB), 10 μg/mL, InRt = (9.6 ± 9.4)%, control Elastatinal, IC50 = (30.8 ± 5.7)μg/mL). Ref: C. -Y. Kao, et al, Mar. Drugs, 2011, 9, 1319 O H

OH

651 Lobocrassin D Type: Cembrane diterpenoids. C22H34O3 Colorless oil, [α]D25 = +71° (c = 0.57, CHCl3). Source: Soft coral Lobophytum crassum (Northeast Taiwan). Pharm: Cytotoxic (K562,

214

3 Diterpenoids

IC50 = 24.00 μg/mL, control Doxorubicin, IC50 = 0.24 μg/mL; CCRF-CEM, IC50 = 10.53 μg/mL, Doxorubicin, IC50 = 0.05 μg/mL; Molt4, IC50 = 10.99 μg/mL, Doxorubicin, IC50 = 0.07 μg/mL; HepG2, IC50 = 34.91 μg/mL, Doxorubicin, IC50 = 0.71 μg/mL; Huh7, IC50 > 40 μg/mL, Doxorubicin, IC50 = 0.46 μg/mL); anti-inflammatory (Hmn neutrophils, inhibits generation of superoxide anion, 10 μg/mL, InRt = (−1.9 ± 7.3)%, control DPI, IC50 = (0.8 ± 0.2)μg/mL); elastase release inhibitor (hmn neutrophils, response to formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB), 10 μg/mL, InRt = (11.0 ± 3.9)%, control Elastatinal, IC50 = (30.8 ± 5.7)μg/mL). Ref: C. -Y. Kao, et al, Mar. Drugs, 2011, 9, 1319 O H

O O

652 Lobocrassin E Type: Cembrane diterpenoids. C20H32O2 Colorless oil, [α]D25 = +47° (c = 0.05, CHCl3). Source: Soft coral Lobophytum crassum (Northeast Taiwan). Pharm: Antiinflammatory (Hmn neutrophils, inhibits generation of superoxide anion, 10 μg/mL, InRt = (−1.2 ± 1.5)%, control DPI, IC50 = (0.8 ± 0.2)μg/mL); elastase release inhibitor (hmn neutrophils, response to formyl-Met-Leu-Phe/Cytochalasin B (fMLP/CB), 10 μg/ mL, InRt = (−4.4 ± 9.5)%, control Elastatinal, IC50 = (30.8 ± 5.7)μg/mL). Ref: C. -Y. Kao, et al, Mar. Drugs, 2011, 9, 1319 O H HO

653 Lobocrassin F Type: Cembrane diterpenoids. C20H30O2 Source: Soft coral Lobophytum crassum (Northeast Taiwan). Pharm: Antioxidant (superoxide anion scavenger, IC50 > 10 μg/mL; 10 μg/mL, InRt = (7.80 ± 5.23)%, control DPI, IC50 = (0.80 ± 0.31)μg/mL); elastase release inhibitor (stimulated hmn neutrophils, response to fMLP/CB, IC50 = (6.27 ± 1.91)μg/mL, 10 μg/mL, InRt = (58.29 ± 5.47)%, control Elastatinal, IC50 = (31.82 ± 5.92)μg/mL). Ref: C. -H. Lee, et al, Mar. Drugs, 2012, 10, 427

3.13 Cembrane Diterpenoids

215

OH O

654 (7Z)-Lobocrassolide Type: Cembrane diterpenoids. C20H30O4 Source: Soft coral Lobophytum sp. (Vietnam). Pharm: Cytotoxic (A549, IC50 = 31.4 μmol/L, control Mitoxantrone, IC50 = 6.1 μmol/L; HT29, IC50 = 22.0 μmol/L, control Mitoxantrone, IC50 = 6.5 μmol/L). Ref: H. T. Nguyen, et al, Arch. Pharm. Res. 2010, 33, 503 O

O

3E 7Z 2

O 11E

1

O

655 Lobocrassolide Type: Cembrane diterpenoids. C22H30O4 Colorless prisms, mp 98–100 °C, [α]D25 = +81.6° (c = 1.2, CHCl3). Source: Soft coral Lobophytum crassum (Taiwan Waters). Pharm: Cytotoxic (A549, ED50 = 2.99 μg/mL, HT29, ED50 = 2.70 μg/mL, KB, ED50 = 2.91 μg/mL, P388, ED50 = 0.012 μg/mL). Ref: C. -Y. Duh, et al, JNP, 2000, 63, 884 O

O

7E

O

3E

O

2 1

11E

656 (7E)-Lobohedleolide Type: Cembrane diterpenoids. C20H26O4 Oil, [α]D = +61.4° (c = 1.01, CHCl3), [α]D = +35° (c = 0.07, CHCl3). Source: Soft corals Lobophytum crassum. and Lobophytum hedleyi. Pharm: Anti-HIV (cell-based in vitro assay, EC50 = 3.6 μg/mL, IC50 = 9.0 μg/ mL, with maximum cellular protection 55%–70%); growth inhibitor; anti-inflammatory (10 μmol/L, inhibits accumulation of pro-inflammatory proteins iNOS and COX2); cytotoxic (Ca9-22, IC50 = 2.8 μg/mL, control Doxorubicin, IC50 = 0.1 μg/mL; HepG2, IC50 > 5.0 μg/mL; Hep3B, IC50 = 4.7 μg/mL; MDA-MB-231, IC50 > 5.0 μg/mL; MCF7, IC50 > 5.0 μg/mL; A549, IC50 = 4.6 μg/mL). Ref: M. A. Rashid, et al, JNP 2000, 63, 531│C. -H. Chao, et al, JNP 2008, 71, 1819

216

3 Diterpenoids

O O

7E

O

2

HO

657 (7Z)-Lobohedleolide Type: Cembrane diterpenoids. C20H26O4 Cryst. (EtOH), mp 183–184 °C, [α]D = + 104.2° (c = 1.12, CHCl3). Source: Soft corals Lobophytum hedleyi, Lobophytum crassum and Lobophytum sp. (aqueous extract). Pharm: Anti-HIV (cell-based in vitro assay, EC50 = 4.6 μg/mL, IC50 = 7.6 μg/mL, with maximum cellular protection 55%– 70%); cytotoxic (A549, IC50 = 42.6 μmol/L, control Mitoxantrone, IC50 = 6.1 μmol/L; HT29, IC50 = 35.5 μmol/L, Mitoxantrone, IC50 = 6.5 μmol/L). Ref: Y. Uchio, et al, Tet. Lett., 1981, 22, 4089│M. A. Rashid, et al, JNP 2000, 63, 531│H. T. Nguyen, et al, Arch. Pharm. Res. 2010, 33, 503 O

O 7Z 2

O OH

658 Lobolide Type: Cembrane diterpenoids. C22H30O5 Cryst., mp 114–115 °C, [α]D = −58° (c = 2.7, CHCl3), Source: Soft coral Lobophytum crassum. Pharm: Ichthyotoxic. Ref: Y. Kashman, et al, Tet. Lett., 1977, 1159│Y. Kashman, et al, JOC, 1981, 46, 3592│Z. Kinamoni, et al, Tetrahedron, 1983, 39, 1643 O

O

18

O 4S

3R 1R 16

14S

O

O

659 Lobomichaolide Type: Cembrane diterpenoids. C24H32O7 Colorless prism, mp 180–181 °C, [α]D25 = + 55.6° (c = 0.1, CHCl3). Source: Soft coral Lobophytum michaelae (Pingtung county, Taiwan). Pharm: Cytotoxic (A549, ED50 = 1.9 μg/mL; HT29, ED50 = 1.4 μg/mL; P388, ED50 = 0.4 μg/mL; HEL, ED50 = 1.7 μg/mL). Ref: S. -K. Wang, et al, JNP, 1992, 55, 1430; 2009, 72, 324 (structure corrected)│S. -K. Wang, et al, Mar. Drugs, 2012, 10, 306

3.13 Cembrane Diterpenoids

O O

217

O

H O

O

O

O

660 Lobophylin A Type: Cembrane diterpenoids. C20H32O3 Colorless oil, [α]D25 = −45° (c = 0.3, CHCl3), [α]D25 = −39° (c = 0.3, CHCl3). Source: Soft corals Lobophytum crassum (Cultured, Pingtung county, Taiwan) and Lobophytum sp. (Dongsha Atoll, South China Sea). Pharm: Anti-inflammatory (immunoblot analysis assay, 10 μmol/L, RAW264.7 macrophage cells, inhibition of LPS induced upregulation of iNOS and COX-2). Ref: N. -L. Lee, et al, Mar. Drugs, 2011, 9, 2526│M. E. F. Hegazy,et al, Mar. Drugs, 2011, 9, 1243 OH H

O O

661 Lobophylin B Type: Cembrane diterpenoids. C20H32O2 Colorless oil, [α]D25 = −30° (c = 0.5, CHCl3), [α]D25 = −35° (c = 0.3, CHCl3). Source: Soft corals Lobophytum crassum (Cultured, Pingtung county, Taiwan) and Lobophytum sp. (Dongsha Atoll, South China Sea). Pharm: Anti-inflammatory (immunoblot analysis assay, 10 μmol/L, RAW264.7 macrophage cells, inhibition of LPS induced upregulation of iNOS and COX-2). Ref: N. -L. Lee, et al, Mar. Drugs, 2011, 9, 2526│M. E. F. Hegazy,et al, Mar. Drugs, 2011, 9, 1243 OH H O

218

3 Diterpenoids

662 Lobophynin C Type: Cembrane diterpenoids. C21H30O4 [α]D25 = +109.3° (c = 0.31, CHCl3). Source: Soft coral Lobophytum schoedei (Japan waters). Pharm: Ichthyotoxic; toxic (brine shrimp lethality). Ref: K. Yamada, et al, JNP, 1997, 60, 798

O O O H

O

663 Lobophytolide (1R,3E,7E,11S,12S,14S)-11,12-Epoxy-3,7,15(17)-cembratrien-16,14-olide Type: Cembrane diterpenoids. C20H28O3 Cryst., mp 137–138 °C, [α]D = +7° (c = 0.4, CHCl3). Source: Soft corals Lobophytum cristagalli and Lobophytum crassum. Pharm: Cytotoxic (farnesyl protein transferase (FPT) inhibitor, IC50 = 0.15 μmol/L); ichthyotoxin (LD50 = 12 mg/L). Ref: B. Tursch, et al, Tet. Lett., 1974, 3769│B. Tursch, Pure Appl. Chem., 1976, 48, 1│R. Karlsson, Acta Crystallogr., Sect. B, 1977, 33, 2032│Ren-lin Zou, et al, 1989, Corals and their Medical useage, Science Press, Beijing.│S.J. Coval, et al, A BoMCL 1996, 6, 909

1R 7E

3E

14S

O

O 12S

11S

O

H

664 Lobophytone U Type: Cembrane diterpenoids. C41H64O9 Source: Soft coral Lobophytum pauciflorum (Hainan I., South China Sea). Pharm: NO production inhibitor (LPS-stimulated mouse macrophages). Ref: P. Yan, et al, Chem. Biodivers., 2011, 8, 1724 O

O COOMe O

H

H HO

HO

O

OH

3.13 Cembrane Diterpenoids

219

665 Lobophytone V Type: Cembrane diterpenoids. C41H64O10 Source: Soft coral Lobophytum pauciflorum (Hainan I., South China Sea). Pharm: NO production inhibitor (LPS-stimulated mouse macrophages). Ref: P. Yan, et al, Chem. Biodivers., 2011, 8, 1724 O

O COOMe O

H

H

HO

O

HO

OH

HO

666 Lobophytone W Type: Cembrane diterpenoids. C43H68O9 Source: Soft coral Lobophytum pauciflorum (Hainan I., South China Sea). Pharm: NO production inhibitor (LPS-stimulated mouse macrophages). Ref: P. Yan, et al, Chem. Biodivers., 2011, 8, 1724 O

O COOMe O

H

H HO

O

O

HO

667 Lobophytone X Type: Cembrane diterpenoids. C41H64O8 Source: Soft coral Lobophytum pauciflorum (Hainan I., South China Sea). Pharm: NO production inhibitor (LPS-stimulated mouse macrophages). Ref: P. Yan, et al, Chem. Biodivers., 2011, 8, 1724

220

3 Diterpenoids

O

O COOMe O

H

H

O

OH

HO

668 Lobophytone Y Type: Cembrane diterpenoids. C43H66O8 Source: Soft coral Lobophytum pauciflorum (Hainan I., South China Sea). Pharm: NO production inhibitor (LPS-stimulated mouse macrophages). Ref: P. Yan, et al, Chem. Biodivers., 2011, 8, 1724 O

O COOMe O

H

H

O

O

HO

669 Lobophytone Z Type: Cembrane diterpenoids. C41H62O8 Source: Soft coral Lobophytum pauciflorum (Hainan I., South China Sea). Pharm: NO production inhibitor (LPS-stimulated mouse macrophages). Ref: P. Yan, et al, Chem. Biodivers., 2011, 8, 1724 O

O COOMe O

H

H O HO

OH

3.13 Cembrane Diterpenoids

221

670 Lobophytone Z1 Type: Cembrane diterpenoids. C43H68O9 Source: Soft coral Lobophytum pauciflorum (Hainan I., South China Sea). Pharm: NO production inhibitor (LPS-stimulated mouse macrophages). Ref: P. Yan, et al, Chem. Biodivers., 2011, 8, 1724 O

O COOMe O

H

H

O

O

OH

HO

671 Lophotoxin 11α,12α-Epoxy-(1R,7S,8S,10S,13R)-3,6:7,8-diepoxy-13-acetoxy-18-oxo-3,5,11,15-cembratetraen-20,10-olide Type: Cembrane diterpenoids. C22H24O8 Cryst. (EtOAc/2,3,3trimethylpentane), mp 164–166 °C, [α]D27 = +14.2° (c = 1.7, CHCl3). Source: Gorgonians Lophogorgia alba, Leptogorgia laxa, Lophogorgia cuspidata and Lophogorgia rigida, soft coral Sinularia polydactyla. Pharm: Potent neuromuscular toxin; muscle relaxant; insecticide; nematocide. Ref: R. S. Jacobs, et al, Tetrahedron, 1985, 41, 981│S. N. Abramson, et al, J. Biol. Chem., 1988, 263, 18568; 1989, 264, 12666│S. N. Abramson, et al, Drug Dev. Res., 1991, 24, 297│S. N. Abramson, et al, JMC, 1991, 34, 1798│C. Tornøe, et al, Toxicon, 1995, 33, 411 O 18 5

H O

O

7S

3

1 15

8S

O 11 12

O

O

O O

672 Methyl sartortuoate Type: Cembrane diterpenoids. C41H62O8 Cryst., mp 246–246.5 °C, [α]D28 = +196° (c = 0.05, EtOH). Source: Soft corals Lobophytum pauciflorum (Hainan I., South China Sea) and Sarcophyton tortuosum. Pharm: NO production inhibitor (LPS-stimulated mouse macrophages). Ref: J. Su, et al, Sci. Sin., Ser. B: (Engl. edn.), 1988, 31,

222

3 Diterpenoids

1172│W. -J. Lan, et al, Youji Huaxue, 2005, 25, 1465│P. Yan, et al, Chem. Biodivers., 2011, 8, 1724 O

O O O O

H

H

H OH O

HO

673 Michaolide L Type: Cembrane diterpenoids. C22H30O6 White amorphous powder, [α]D25 = +13.3° (c = 0.1, CHCl3). Source: Soft coral Lobophytum michaelae (Pingtung county, Taiwan). Pharm: Cytotoxic (A549, ED50 = 1.2 μg/mL; HT29, ED50 = 0.8 μg/mL; P388, ED50 = 0.3 μg/mL; HEL, ED50 = 1.0 μg/mL). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 306 O

O O H OH O

O

674 Michaolide M Type: Cembrane diterpenoids. C26H34O9 White amorphous powder, [α]D25 = + 11.2° (c = 0.1, CHCl3). Source: Soft coral Lobophytum michaelae (Pingtung county, Taiwan). Pharm: Cytotoxic (A549, ED50 = 2.0 μg/mL; HT29, ED50 = 4.9 μg/mL; P388, ED50 = 1.5 μg/mL; HEL, ED50 = 3.2 μg/mL). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 306 O O O

O O H O O

O

O

3.13 Cembrane Diterpenoids

223

675 Michaolide N Type: Cembrane diterpenoids. C26H32O10 White amorphous powder, [α]D25 = +7.6° (c = 0.1, CHCl3). Source: Soft coral Lobophytum michaelae (Pingtung county, Taiwan). Pharm: Cytotoxic (A549, ED50 = 2.1 μg/mL; HT29, ED50 = 1.6 μg/mL; P388, ED50 = 0.4 μg/mL; HEL, ED50 = 2.0 μg/mL). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 306 O O O

O O

O H

O

O O

O

H

676 Michaolide O Type: Cembrane diterpenoids. C26H36O11 White amorphous powder, [α]D25 = + 3.1° (c = 0.1, CHCl3). Source: Soft coral Lobophytum michaelae (Pingtung county, Taiwan). Pharm: Cytotoxic (A549, ED50 = 61.3 μg/mL; HT29, ED50 = 61.5 μg/mL; P388, ED50 = 39.6 μg/mL; HEL, ED50 = 60.2 μg/mL). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 306 O O

O O

O

H

O

OH

O

O O O

677 Michaolide P Type: Cembrane diterpenoids. C22H30O5 White amorphous powder, [α]D25 = + 122.0° (c = 0.1, CHCl3). Source: Soft coral Lobophytum michaelae (Pingtung county, Taiwan). Pharm: Cytotoxic (A549, ED50 = 3.2 μg/mL; HT29, ED50 = 2.8 μg/mL; P388, ED50 = 2.0 μg/mL; HEL, ED50 = 2.9 μg/mL). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 306 O

O

H OH O

O

224

3 Diterpenoids

678 Michaolide Q Type: Cembrane diterpenoids. C26H34O8 White amorphous powder, [α]D25 = +81.6° (c = 0.1, CHCl3). Source: Soft coral Lobophytum michaelae (Pingtung county, Taiwan). Pharm: Cytotoxic (A549, ED50 = 2.0 μg/mL; HT29, ED50 = 1.5 μg/mL; P388, ED50 = 1.0 μg/mL; HEL, ED50 = 1.8 μg/mL). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 306 O O

O

O

H O O

O O

679 (–)-Nephthenol‡ (1R,3E,7E,11E)-3,7,11-Cembratrien-15-ol Type: Cembrane diterpenoids. C20H34O Oil, bp0.03mmHg 96 °C, [α]D = −36° (c = 0.2, CHCl3). Source: Soft corals Nephthea spp. and Litophyton viridis. Pharm: Hypotensive. Ref: S. Carmely, et al, JOC, 1981, 46, 4279│A. J. Blackman, et al, Aust. J. Chem., 1982, 35, 1873│Y. P. Shi, et al, JNP, 2001, 64, 1439

OH 1R

680 Nyalolide Type: Cembrane diterpenoids. C43H66O10 Cryst., [α]D25 = +98° (c = 0.08, CHCl3). Source: Soft corals Lobophytum pauciflorum (Hainan I., South China Sea) and Sarcophyton glaucum. Pharm: NO production inhibitor (LPS-stimulated mouse macrophages). Ref: M. Feller, et al, JNP, 2004, 67, 1303│P. Yan, et al, Chem. Biodivers., 2011, 8, 1724

O

O O

O O H

H

H O

O O HO

H

OH

3.13 Cembrane Diterpenoids

225

681 Pachyclavulariolide F Type: Cembrane diterpenoids. C29H46O7 White amorphous solid, [α]D = +32.1° (c = 1.22 g/100 ml, MeOH). Source: Soft coral Pachyclavularia violacea (Papua New Guinea). Pharm: Cytotoxic (P388, IC50 = 1.0 μg/mL). Ref: L. Xu, et al, Tetrahedron, 2000, 56, 9031

O O O

HO

O

O O

682 Pachyclavulariolide I Type: Cembrane diterpenoids. C20H30O5 Solid, mp 188–189 °C, [α]D28 = +88° (c = 1.03, CHCl3). Source: Soft coral Pachyclavularia violacea. Pharm: Cytotoxic (P388 mouse lymphocytic leukemia cell, ED50 = 1.3 μg/mL). Ref: J. H. Sheu, et al, Tetrahedron, 2001, 57, 7639 OH OH O O

O

683 Pachyclavulariolide J Type: Cembrane diterpenoids. C26H38O8 Oil, [α]D25 = −47° (c = 0.36, CHCl3). Source: Soft coral Pachyclavularia violacea. Pharm: Cytotoxic (P388 mouse lymphocytic leukemia cell, ED50 = 2.5 μg/mL). Ref: J. H. Sheu, et al, Tetrahedron, 2001, 57, 7639 O O O O

3 2

O

O O OH

684 Pavidolide A Type: Cembrane diterpenoids. C21H30O4 [α]D20 = +124.0° (c = 0.25, CHCl3). Source: Soft coral Sinularia pavida (Sanya Bay, Hainan, China). Pharm: Cytotoxic (HL60, HCT8, HepG2, BGC823, A549, and A375, all IC50s > 10 μg/mL). Ref: S. Shen, et al, Tetrahedron Lett., 2012, 53, 5759

226

3 Diterpenoids

O O O O

685 Pavidolide B Type: Cembrane diterpenoids. C20H26O4 Source: Soft coral Sinularia pavida (Sanya Bay, Hainan, China). Pharm: Cytotoxic (HL60, IC50 = 2.7 μg/mL); cytotoxic (HCT8, HepG2, BGC823, A549, and A375, all IC50s > 10 μg/mL). Ref: S. Shen, et al, Tetrahedron Lett., 2012, 53, 5759 O H H

O

H

O

H O

686 Pavidolide C Type: Cembrane diterpenoids. C21H30O5 Source: Soft coral Sinularia pavida (Sanya Bay, Hainan, China). Pharm: Cytotoxic (HL60, IC50 = 5.3 μg/mL); cytotoxic (HCT8, HepG2, BGC823, A549, and A375, all IC50s > 10 μg/mL); antifoulant (inhibits larval settlement of Balanus Amphitrite, ED50 = 4.32 μg/mL with low cytotoxicity LD50 > 50 μg/mL). Ref: S. Shen, et al, Tetrahedron Lett., 2012, 53, 5759 H O H O

O

O

O

687 Pavidolide D Type: Cembrane diterpenoids. C20H34O2 Source: Soft coral Sinularia pavida (Sanya Bay, Hainan, China). Pharm: Cytotoxic (HL60, HCT8, HepG2, BGC823, A549, and A375, all IC50s > 10 μg/mL).; antifoulant (inhibits larval settlement of Balanus Amphitrite, ED50 = 2.12 μg/mL with low cytotoxicity LD50 > 50 μg/mL). Ref: S. Shen, et al, Tetrahedron Lett., 2012, 53, 5759

3.13 Cembrane Diterpenoids

227

OH H

OH

H

688 Pavidolide E Type: Cembrane diterpenoids. C20H34O2 Source: Soft coral Sinularia pavida (Sanya Bay, Hainan, China). Pharm: Cytotoxic (HL60, HCT8, HepG2, BGC823, A549, and A375, all IC50s > 10 μg/mL). Ref: S. Shen, et al, Tetrahedron Lett., 2012, 53, 5759 OH H

OH

H

689 Petronigrione Type: Cembrane diterpenoids. C41H62O8 Source: Sponge Petrosia nigricans (Haivan, Danang, Vietnam). Pharm: Cytotoxic (HTCLs, moderate). Ref: N. X. Nhiem, et al, Nat. Prod. Commun., 2013, 8, 1209 O

O

O OH

O

OH

H O O

690 Pseudoplexaurol Type: Cembrane diterpenoids. C20H32O2 Oil, [α]D26 = −21.5° (c = 3.4, CHCl3). Source: Gorgonian Pseudoplexaura porosa (Caribbean Sea), soft coral Lobophytum crassum (Northeast Taiwan). Pharm: Cytotoxic (MCF7, IC50 = 20 μg/mL; HCT116, IC50 = 10 μg/mL; CCRF-CEM, IC50 = 0.15 μg/mL). Ref: A. D. Rodriguez, et al, Experientia, 1993, 49, 179│A. D. Rodriguez, et al, JNP, 1993, 56, 1101│C. -Y. Kao, et al, Mar. Drugs, 2011, 9, 1319

228

3 Diterpenoids

O 16

OH

691 Pukalide Methyl (1R,7S,8R,10S)-3,6:7,8-Diepoxy-3,5,11,15-cembratetraen-20,10-olid-18-oate Type: Cembrane diterpenoids. C21H24O6 Cryst. (MeOH), mp 204–206 °C, [α]D = +44° (c = 1.1, CHCl3), [α]D24 = +42° (c = 0.57, CHCl3). Source: Soft corals Sinularia abrupta (Hawaii), Sinularia polydactyla and Sinularia erecta, gorgonians Lophogorgia alba, Lophogorgia chilensis, Lophogorgia cuspidata, Leptogorgia virgulata and Lophogorgia rigida, nudibranch Tochuina tetraquetra. Pharm: Ichthyotoxin, antifoulant; LD50 (mus, scu) = 8 mg/kg. Ref: M. G. Missakian, et al, Tetrahedron, 1975, 31, 2513│M. B. Ksebati, et al, JNP (Lloydia), 1984, 47, 1009│D. J. Gerhart, et al, J. Chem. Ecol. 1988, 14, 1905; 1993, 19, 2697│CRC Press, DNP on DVD, 2012, version 20.2 O O 18

5 7S

H O

8R

O

3

1 15

11

12

O O

692 Querciformolide A (1R,3S,4R,7S,8R,12R)-4,8-Epoxy-3-hydroxy-7-acetoxy-11-oxo-15(17)-cembren-16,12-olide Type: Cembrane diterpenoids. C22H32O7 Powder, mp 120–122 °C, [α]D25 = −2.6° (c = 0.8, CHCl3). Source: Soft coral Sinularia querciformis. Pharm: Cytotoxic (HeLa, Hep2, Doay, MCF7, all ED50s > 20 μg/mL). Ref: Y. Lu, et al, JNP, 2008, 71, 1754 11

O

O O

O O

7 3

OH

O

3.13 Cembrane Diterpenoids

229

693 Querciformolide B Notandolide Type: Cembrane diterpenoids. C22H34O7 Cryst., mp 109–111 °C, [α]D25 = −28° (c = 0.6, CHCl3). Source: Soft corals Sinularia querciformis, Sinularia notanda and Sinularia granosa. Pharm: Cytotoxic (HeLa, Hep2, Doay, MCF7, all ED50s > 20 μg/mL). Ref: A. F. Ahmed, et al, Mansoura J. Pharm. Sci., 2007, 23, 27│Y. Lu, et al, JNP, 2008, 71, 1754 O O

O O 11R

H O HO

OH

694 Querciformolide C Type: Cembrane diterpenoids. C24H36O8 Powder, mp 149–150 °C, [α]D25 = + 0.96° (c = 1, CHCl3). Source: Soft corals Sinularia querciformis and Sinularia granosa. Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/ L: inhibits up-regulation of pro-inflammatory iNOS to 23.7% compare with control LPS-stimulated cells alone); cytotoxic (HeLa, Hep2, Doay, MCF7, all ED50 > 20 μg/ mL). Ref: Y. Lu, et al, JNP, 2008, 71, 1754 O O

O O O

HO

O O

695 Querciformolide D (1R,3S,4R,7S,8R,11R,12R)-4,7-Epoxy-3,8,11-trihydroxy-15(17)-cembren-16,12-olide Type: Cembrane diterpenoids. C20H32O6 Powder, mp 111–113 °C, [α]D25 = −2° (c = 0.4, CHCl3). Source: Soft coral Sinularia querciformis. Pharm: Cytotoxic (HeLa, Hep2, Doay, MCF7, all ED50 > 20 μg/mL). Ref: Y. Lu, et al, JNP, 2008, 71, 1754 O O HO 11R

O HO

OH

230

3 Diterpenoids

696 JNP711819-11 Type: Cembrane diterpenoids. C22H30O6 Source: Soft coral Lobophytum crassum. Pharm: Anti-inflammatory (10 μmol/L, inhibits accumulation of pro-inflammatory proteins iNOS and COX-2); cytotoxic (Ca9-22, IC50 = 1.2 μg/mL, control Doxorubicin, IC50 = 0.1 μg/mL; HepG2, IC50 = 2.4 μg/mL, Doxorubicin, IC50 = 0.2 μg/mL; Hep3B, IC50 = 2.5 μg/mL, Doxorubicin, IC50 = 0.2 μg/mL; MDA-MB-231, IC50 = 2.0 μg/mL, Doxorubicin, IC50 = 0.2 μg/mL; MCF7, IC50 = 2.0 μg/mL, Doxorubicin, IC50 = 0.2 μg/ mL; A549, IC50 = 2.3 μg/mL, Doxorubicin, IC50 = 0.2 μg/mL). Ref: C. -H. Chao, et al, JNP, 2008, 71, 1819 O O

O

O O

O

697 Sarcocrassocolide A Type: Cembrane diterpenoids. C22H30O6 Source: Soft coral Sarcophyton crassocaule (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (mild); inhibits expression of iNOS (macrophages). Ref: W. -Y. Lin, et al, BoMC, 2010, 18, 1936 OH H

O

O O O

O

698 Sarcocrassocolide B Type: Cembrane diterpenoids. C22H30O6 Source: Soft coral Sarcophyton crassocaule (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (mild); inhibits expression of iNOS (macrophages). Ref: W. -Y. Lin, et al, BoMC, 2010, 18, 1936 OH H

O

O O O

O

699 Sarcocrassocolide C Type: Cembrane diterpenoids. C20H28O4 Source: Soft coral Sarcophyton crassocaule (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (mild); inhibits expression of iNOS (macrophages). Ref: W. -Y. Lin, et al, BoMC, 2010, 18, 1936

3.13 Cembrane Diterpenoids

231

OH H

O

O

O

700 Sarcocrassocolide D Type: Cembrane diterpenoids. C20H28O4 Source: Soft coral Sarcophyton crassocaule (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (mild); inhibits expression of iNOS (macrophages). Ref: W. -Y. Lin, et al, BoMC, 2010, 18, 1936 OH H O

O

O

701 Sarcocrassocolide E Type: Cembrane diterpenoids. C23H32O5 Source: Soft coral Sarcophyton crassocaule (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (mild); inhibits expression of iNOS (macrophages). Ref: W. -Y. Lin, et al, BoMC, 2010, 18, 1936 O H

O O

O

O

702 Sarcocrassocolide F Type: Cembrane diterpenoids. C22H30O7 White solid; mp 92.0–95.0 °C, [α]D25 = −42° ( c = 0.6, CHCl3). Source: Soft coral Sinularia crassocaule (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (Doay, ED50 = (7.3 ± 1.7)μmol/L, control Mitomycin C, ED50 = (0.44 ± 0.06)μmol/L; Hep2, ED50 = (15.0 ± 1.9)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.06)μmol/L; MCF7, ED50 = (19.4 ± 2.4)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.12)μmol/ L; WiDr, ED50 = (18.4 ± 0.9)μmol/L, Mitomycin C, ED50 = (0.47 ± 0.12)μmol/L); inhibits up-regulation of pro-inammatory protein iNOS (LPS-induced). Ref: W. -Y. Lin, et al, Mar. Drugs, 2011, 9, 994 O

H

O O

HO

O

8

13

O

O

232

3 Diterpenoids

703 Sarcocrassocolide G Type: Cembrane diterpenoids. C22H30O7 Colorless oil, [α]D25 = −56° ( c = 0.6, CHCl3). Source: Soft coral Sinularia crassocaule (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (Doay, ED50 = (8.3 ± 1.4)μmol/L, control Mitomycin C, ED50 = (0.44 ± 0.06) μmol/L; Hep2, ED50 = (16.5 ± 1.7)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.06)μmol/L; MCF7, ED50 = (9.6 ± 2.7)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.12)μmol/L; WiDr, ED50 = (18.9 ± 1.9)μmol/L, Mitomycin C, ED50 = (0.47 ± 0.12)μmol/L); inhibits up-regulation of pro-inammatory protein iNOS (LPS-induced). Ref: W. -Y. Lin, et al, Mar. Drugs, 2011, 9, 994 O

H

O O

HO

13

8

O

O

O

704 Sarcocrassocolide H Type: Cembrane diterpenoids. C22H30O6 Colorless oil, [α]D25 = −17° ( c = 0.5, CHCl3). Source: Soft coral Sinularia crassocaule (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (Doay, ED50 = (6.4 ± 2.0)μmol/L, control Mitomycin C, ED50 = (0.44 ± 0.06)μmol/L; Hep2, ED50 = (13.5 ± 2.5)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.06) μmol/L; MCF7, ED50 = (9.4 ± 2.5)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.12)μmol/L; WiDr, ED50 = (18.7 ± 1.0)μmol/L, Mitomycin C, ED50 = (0.47 ± 0.12)μmol/L); inhibits up-regulation of pro-inammatory protein iNOS (LPS-induced). Ref: W. -Y. Lin, et al, Mar. Drugs, 2011, 9, 994 O

H

O O

HO

8

13

O

O

705 Sarcocrassocolide I Type: Cembrane diterpenoids. C22H30O6 Colorless oil, [α]D25 = −29° ( c = 0.4, CHCl3). Source: Soft coral Sinularia crassocaule (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (Doay, ED50 = (5.1 ± 1.2)μmol/L, control Mitomycin C, ED50 = (0.44 ± 0.06) μmol/L; Hep2, ED50 = (5.8 ± 0.5)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.06)μmol/L; MCF7, ED50 = (8.4 ± 1.5)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.12)μmol/L; WiDr, ED50 = (6.4 ± 2.0)μmol/L, Mitomycin C, ED50 = (0.47 ± 0.12)μmol/L); inhibits up-regulation of pro-inammatory protein iNOS (LPS-induced). Ref: W. -Y. Lin, et al, Mar. Drugs, 2011, 9, 994

3.13 Cembrane Diterpenoids

O

H

O O

13

8

HO

233

O

O

706 Sarcocrassocolide J Type: Cembrane diterpenoids. C20H28O5 Colorless oil, [α]D25 = −142° ( c = 0.1, CHCl3). Source: Soft coral Sinularia crassocaule (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (Doay, Hep2, MCF7 and WiDr, all ED50s > 20 μmol/L); inhibits up-regulation of pro-inammatory protein iNOS (LPS-induced). Ref: W. -Y. Lin, et al, Mar. Drugs, 2011, 9, 994 O

H

O O

HO

13

8

O

707 Sarcocrassocolide K Type: Cembrane diterpenoids. C20H28O4 Colorless oil, [α]D25 = −51° ( c = 0.3, CHCl3). Source: Soft coral Sinularia crassocaule (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (Doay, ED50 = (9.9 ± 4.0)μmol/L, control Mitomycin C, ED50 = (0.44 ± 0.06)μmol/L; Hep2, ED50 = > 20 μmol/L, Mitomycin C, ED50 = (0.30 ± 0.06) μmol/L; MCF7, ED50 = (10.2 ± 1.0)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.12)μmol/L; WiDr, ED50 > 20 μmol/L, Mitomycin C, ED50 = (0.47 ± 0.12)μmol/L); inhibits up-regulation of pro-inammatory protein iNOS (LPS-induced). Ref: W. -Y. Lin, et al, Mar. Drugs, 2011, 9, 994 O

H

O O

HO

8

13

708 Sarcocrassocolide L Type: Cembrane diterpenoids. C20H28O4 White solid; mp 85–87 °C, [α]D25 = −140° ( c = 0.2, CHCl3). Source: Soft coral Sinularia crassocaule (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (Doay, Hep2, MCF7 and WiDr, all ED50s > 20 μmol/L); inhibits up-regulation of pro-inammatory protein iNOS (LPS-induced). Ref: W. -Y. Lin, et al, Mar. Drugs, 2011, 9, 994

234

3 Diterpenoids

O

H

O O

HO

13

8

709 Sarcocrassocolide M Type: Cembrane diterpenoids. C22H30O7 Colorless oil, [α]D25 = −61° (c = 0.4, CHCl3). Source: Soft coral Sarcophyton crassocaule 20070402 (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (Doay, ED50 = (6.6 ± 0.8)μmol/L, control Mitomycin C, ED50 = (0.44 ± 0.06)μmol/L; Hep2, ED50 = (10.4 ± 1.1)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.06)μmol/L; MCF7, ED50 = (10.6 ± 0.5)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.12) μmol/L; WiDr, ED50 > 40 μmol/L, Mitomycin C, ED50 = (0.47 ± 0.12)μmol/L); anti-inflammatory (in vitro LPS-stimulated RAW264.7 macrophage cells, inhibits expression of iNOS protein; inhibits induction of iNOS protein, significant). Ref: W. -Y. Lin, et al, Mar. Drugs, 2012, 10, 617 O H O

O O

OH

O

O

710 Sarcocrassocolide N Type: Cembrane diterpenoids. C22H30O7 Colorless oil, [α]D25 = −153° (c = 0.2, CHCl3). Source: Soft coral Sarcophyton crassocaule 20070402 (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (Doay, ED50 = (5.2 ± 0.6)μmol/L, control Mitomycin C, ED50 = (0.44 ± 0.06)μmol/L; Hep2, ED50 = (12.3 ± 1.6)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.06)μmol/L; MCF7, ED50 = (10.1 ± 2.3)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.12) μmol/L; WiDr, ED50 = (30.1 ± 2.8)μmol/L, Mitomycin C, ED50 = (0.47 ± 0.12) μmol/L); anti-inflammatory (in vitro LPS-stimulated RAW264.7 macrophage cells, inhibits expression of iNOS protein; inhibits induction of iNOS protein, significant). Ref: W. -Y. Lin, et al, Mar. Drugs, 2012, 10, 617 O H O

O O

OH O

O

3.13 Cembrane Diterpenoids

235

711 Sarcocrassocolide O Type: Cembrane diterpenoids. C20H28O5 Colorless oil, [α]D25 = −140° (c = 0.2, CHCl3). Source: Soft coral Sarcophyton crassocaule 20070402 (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (Doay, ED50 = (5.0 ± 0.7)μmol/L, control Mitomycin C, ED50 = (0.44 ± 0.06)μmol/L; Hep2, ED50 = (12.4 ± 2.1)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.06)μmol/L; MCF7, ED50 = (6.4 ± 0.5)μmol/L, Mitomycin C, ED50 = (0.30 ± 0.12)μmol/ L; WiDr, ED50 > 40 μmol/L, Mitomycin C, ED50 = (0.47 ± 0.12)μmol/L); anti-inflammatory (in vitro LPS-stimulated RAW264.7 macrophage cells, inhibits expression of iNOS protein; inhibits induction of iNOS protein, significant). Ref: W. -Y. Lin, et al, Mar. Drugs, 2012, 10, 617 O H O

O O

OH

712 Sarcocrassolide Type: Cembrane diterpenoids. C20H28O3 Colorless oil, [α]D25 = +7.8° (c = 0.10, CHCl3). Source: Soft coral Sarcophyton crassocaule (Taiwan Waters). Pharm: Cytotoxic (A549, EC50 = 8.31 μg/mL, HT29, EC50 = 7.55 μg/mL, KB, EC50 = 9.15 μg/mL, P388, EC50 = 0.16 μg/mL). Ref: C. -Y. Duh, et al, JNP, 2000, 63, 1634 O 4S

3S

O

O

713 Sarcoglaucol Type: Cembrane diterpenoids. C21H30O4 Cryst. (Et2O), mp 150–152 °C, [α]D22 = + 177° (c = 0.312, MeOH). Source: Soft coral Sarcophyton glaucum. Pharm: Ichthyotoxin. Ref: M. Albericci, et al, Bull. Soc. Chim. Belg., 1978, 87, 487

O O O OH

236

3 Diterpenoids

714 Sarcolactone A Type: Cembrane diterpenoids. C20H28O3 Source: Soft coral Sarcophyton infundibuliforme (Weizhou coral reef, Guangxi, China). Pharm: Toxic (brine shrimp). Ref: X. -P. Sun, et al, Nat. Prod. Commun., 2010, 5, 1171 HO

O O

715 Sarcophine Type: Cembrane diterpenoids. C20H28O3 Cryst. (Me2CO/petrol), mp 133–134 °C, [α]D25 = +92° (c = 1, CHCl3). Source: Soft corals Sarcophyton glaucum, Sinularia gibberosa and Lobophytum sp. Pharm: Ichthyotoxin; tumorigenesis inhibitor; acetylcholine esterase inhibitor; ATPase inhibitor. Ref: J. Bernstein, et al, Tetrahedron, 1974, 30, 2817│T. Takahashi, et al, JOC, 1992, 57, 3521│Y. Li, et al, Tet. Lett., 1992, 33, 1225│Q. Zheng, et al, Chinese Sci. Bull., 1992, 37, 86 O

O

O

716 Sarcophinone Type: Cembrane diterpenoids. C20H28O3 mp 141–142 °C. Source: Soft corals Sarcophyton decaryi and Sarcophyton molle. Pharm: Cytotoxic (2.5 μg/mL: EAC, InRt = 70%, S180 mouse sarcoma cell, InRt = 53.9%); inhibits CYP450 1A and induces glutathione-S-transferase and quinone reductase activity. Ref: Z. Yan, et al, Redai Haiyang, 1985, 4, 80│Ren-lin Zou, et al, 1989, Corals and their Medical useage, Science Press, Beijing.│J. Y. Su, et al, Chem. J. Chin. Univ., 2001, 22, 1515 O O

O

3.13 Cembrane Diterpenoids

237

717 Sarcophytol A (1Z,3E,7E,11E,14S)-1,3,7,11-Cembratetraen-14-ol Type: Cembrane diterpenoids. C20H32O Oil, [α]D = +115°, [α]D = +206.5° (CHCl3). Source: Soft corals Sarcophyton sp. and Sinularia sp. Pharm: Cytotoxic (P388 cells, ED50 = 1.3 μg/mL; KB, ED50 > 50 μg/mL; A549, ED50 > 50 μg/mL; HT29, ED50 = 23.9 μg/mL). antitumour promoter; ornithine decarboxylase inhibitor; hyperplasia and histamine release inhibitor; antiinflammatory; antipsoriatic. Ref: M. Kobayashi, et al, CPB, 1979, 27, 2382; 1988, 36, 2331; 1989, 37, 631; 2053; 1990, 38, 815│A. J. Blackman, et al, Aust. J. Chem., 1982, 35, 1873│M. Kobayashi, et al, JOC, 1990, 55, 1947│J. -H. Shen, et al, J. Chin. Chem. Soc. (Taipei), 1999, 46, 253│M. Koh, et al, Biosci., Biotechnol., Biochem., 2000, 64, 858│C. A. Gray, et al, JNP, 2000, 63, 1551

OH

718 Sarcophytol B Type: Cembrane diterpenoids. C20H32O2 Cryst. (Me2CO) or colourless oil, mp 125– 126.5 °C, [α]D = +164° (c = 1, CHCl3). Source: Soft corals Sinularia sp. (Bowden Reef, Great Barrier Reef, Australia), Sarcophyton glaucum and Alcyonium flaccidum. Pharm: Cytotoxic (SF268, GI50 = 16 μmol/L, MCF7, GI50 = 12.5 μmol/L, H460, GI50 = 15 μmol/L); anti-inflammatory; antipsoriatic; histamine release inhibitor. Ref: M. Kobayashi, et al, CPB, 1979, 27, 2382; 1989, 37, 631; 37, 2053│Y. Kashman, et al, JOC, 1981, 46, 3592│A. D. Wright, et al, Mar. Drugs, 2012, 10, 1619

HO OH

719 Sarcophytolide‡ (3S,4R,7E,12E,14S)-3,4-Epoxy-1(15),7,12-cembratrien-16,14-olide Type: Cembrane diterpenoids. C20H28O3 Cryst., mp 142 °C. Source: Soft coral Sarcophyton glaucum. Pharm: Antimicrobial (wide range); neuroprotectant. Ref: F. A. Badaria, et al, Int. J. Pharmacogn., 1997, 35, 284│F. A. Badaria, et al, Toxicology, 1998, 131, 133

238

3 Diterpenoids

O

O

O

720 Sarcophytol M (1R,3E,7E,11E)-3,7,11-Cembratrien-1-ol Type: Cembrane diterpenoids. C20H34O Oil, [α]D = +57° (c = 0.94, CHCl3). Source: Soft coral Sarcophyton glaucum. Pharm: Antitumour promoter. Ref: M. Kobayashi, et al, CPB, 1989, 37, 631│Y. Li, et al, Tet. Lett., 1993, 34, 2799│X. Yue, et al, Bull. Chim. Soc. Belg., 1994, 103, 35

OH

721 Sarcrassin A Type: Cembrane diterpenoids. C22H32O5 Yellow oil, [α]D20 = −6.3° (c = 0.208, CHCl3). Source: Soft coral Sarcophyton crassocaule. Pharm: Cytotoxic (KB, IC50 = 19.0 μg/ mL, moderate). Ref: C. Zhang, et al, JNP, 2006, 69, 1476 O

O 3E

O 1Z

O

O

722 Sarcrassin B Type: Cembrane diterpenoids. C22H32O6 Yellow oil, [α]D20 = +6.9° (c = 0.13, CHCl3). Source: Soft coral Sarcophyton crassocaule. Pharm: Cytotoxic (KB, IC50 = 5.0 μg/ mL). Ref: C. Zhang, et al, JNP, 2006, 69, 1476

3.13 Cembrane Diterpenoids

239

O

O

3E

2S

O

O

1R

O

O

723 Sarcrassin D Type: Cembrane diterpenoids. C23H32O6 Yellow oil, [α]D20 = +187° (c = 0.108, CHCl3). Source: Soft coral Sarcophyton crassocaule. Pharm: Cytotoxic (KB, IC50 = 4.0 μg/ mL). Ref: C. Zhang, et al, JNP, 2006, 69, 1476 3E

O

1

O O 7 8

O

11

O O

724 Sarcrassin E Type: Cembrane diterpenoids. C21H28O5 Oil, [α]D20 = +51.5° (c = 1.7, CHCl3). Source: Soft coral Sarcophyton crassocaule. Pharm: Cytotoxic (KB, IC50 = 13.0 μg/mL, moderate). Ref: C. Zhang, et al, JNP, 2006, 69, 1476 O O 7

O O O

725 Sinuflexibilin Type: Cembrane diterpenoids. C21H36O6 Cryst.,mp 169–170 °C, [α]D25 = −3.9° (c = 0.14, MeOH). Source: Soft coral Sinularia flexibilis (Taiwan Waters). Pharm: Cytotoxic (A549, ED50 = 0.72 μg/mL; HT29, ED50 = 0.22 μg/mL; KB, ED50 = 1.73 μg/mL; P388, ED50 = 0.27 μg/mL). Ref: C. -Y. Duh, et al, JNP, 1998, 61,844

240

3 Diterpenoids

HO

O O

OH

OH

OH

726 Sinuflexolide Type: Cembrane diterpenoids. C20H32O5 Cryst., mp 172–173 °C, [α]D25 = −8.6° (c = 0.17, CHCl3). Source: Soft coral Sinularia flexibilis (Taiwan Waters). Pharm: Cytotoxic (A549, ED50 = 0.68 μg/mL; HT29, ED50 = 0.39 μg/mL; KB, ED50 = 0.46 μg/mL; P388, ED50 = 0.16 μg/mL). Ref: C. -Y. Duh, et al, JNP, 1998, 61,844 O

HO O OH

OH

727 Sinugibberol Type: Cembrane diterpenoids. C20H32O3 Crystals, mp 142–144 °C, [α]D = +30.6° (c = 0.011, CHCl3). Source: Soft coral Sinularia gibberosa (Taiwan Waters). Pharm: Cytotoxic (HT29, ED50 = 0.50 μg/mL; P388, ED50 = 11.7 μg/mL). Ref: R. -S. Hou, et al, JNP, 1995, 58, 1126 O

OH

O

728 Sinularcasbane B Type: Cembrane diterpenoids. C20H30O2 Source: Soft coral Sinularia sp. (Ximao I., Hainan, South China Sea). Pharm: NO production inhibitor (stimulated macrophages). Ref: J. Yin, et al, Mar. Drugs, 2013, 11, 455

3.13 Cembrane Diterpenoids

241

O

O

729 Sinularcasbane E Type: Cembrane diterpenoids. C20H32O2 Source: Soft coral Sinularia sp. (Ximao I., Hainan, South China Sea). Pharm: NO production inhibitor (stimulated macrophages). Ref: J. Yin, et al, Mar. Drugs, 2013, 11, 455 O

HO

730 Sinularin Flexibilide Type: Cembrane diterpenoids. C20H30O4 White powder; mp 151–153 °C, [α]D25 = −120° ( c = 0.5, CHCl3); Cryst. (Et2O), mp 150–152 °C, [α]D21 = −115° (c = 1, CHCl3). Source: Soft corals Sinularia sp. (Dongluo I., Hainan, South China Sea), Sinularia triangula (Taitung County, Taiwan), Sinularia flexibilis and Sinularia capillosa. Pharm: Cytotoxic (CCRF-CEM, ED50 = 26.0 μmol/L, control Doxorubicin, ED50 = 0.57 μmol/L, DLD-1, ED50 = 37.1 μmol/L, Doxorubicin, ED50 = 0.25 μmol/L); anti-inflammatory (immunoblot analysis assay, 10 μmol/L, RAW264.7 macrophage cells, inhibition of LPS induced upregulation of iNOS and COX-2, reduced COX-2 to ≈ 85%, reduced iNOS to (1.2 ± 0.3)%); antibacterial (gram-positive bacteria); NF-κB inhibitor (cell-based HEK-293 NF-κB luciferase reporter gene assay, IC50 = 5.30 μg/mL; NF-κB plays a key role in regulating immune response to infection, incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development). Ref: A. J. Weinheimer,et al, Tetrahedron Lett. 1977, 34, 2923│R. Kazlauskas, et al, Aust. J. Chem., 1978, 31, 1817│J. S. Yang, et al, JNP, 2000, 63, 1543│J. -H. Su, et al, Mar. Drugs, 2011, 9, 944│B. Yang, ET AL, Mar. Drugs, 2012, 10, 2023

242

3 Diterpenoids

O

OH

O

H

O

731 (–)-Sinulariol B Type: Cembrane diterpenoids. C20H34O2 Cryst., mp 61–63 °C, [α]D = −52° (c = 1.12, CHCl3). Source: Soft coral Sinularia mayi (Japan waters). Pharm: Precursor to the cembrane lactone found in various soft coral. Ref: M. Kobayashi, et al, CPB, 1987, 35, 2314 OH OH

732 Sinulariolide Type: Cembrane diterpenoids. C20H30O4 Cryst. (C6H6), mp 170–173 °C, [α]D = + 76° (c = 0.7, MeOH). Source: Soft corals Sinularia capillosa and Sinularia flexibilis. Pharm: Cytotoxic (KB, ED50 = 20 μg/mL, PS, ED50 = 7 μg/mL); cytotoxic (P388,ED50 = 8.5 μg/ mL, L1210, ED50 = 10.5 μg/mL); antibacterial (gram-positive bacteria). Ref: B. Tursch, et al, Tetrahedron, 1975, 31, 129│R. Karlsson, Acta Crystallogr., Sect. B, 1977, 33, 2027│Ren-lin Zou, et al, 1989, Corals and their Medical useage, Science Press, Beijing.│J. Y. Su, et al, JNP, 2000, 63, 1543 O

OH

O O

733 11-epi-Sinulariolide Type: Cembrane diterpenoids. C20H30O4 Cryst., mp 166.5–168.5 °C, [α]D = +19.7° (c = 0.5, MeOH). Source: Soft coral Sinularia flexibilis, prosobranch Planaxis sulcatus. Pharm: Antifoulant (strong algicide). Ref: K. Mori, et al, Chem. Lett., 1983, 1515│R. Sanduja, et al, JNP, 1986, 49, 718│K.Michalek, et al,. J. Chem. Ecol. 1997, 23, 259

3.13 Cembrane Diterpenoids

243

O 6

OH

H

16

O

12

O

734 Sinulariol J Type: Cembrane diterpenoids. C20H34O4 Source: Soft coral Sinularia rigida (Sanya Bay, Hainan, China). Pharm: Antifoulant (barnacle Balanus amphitrite). Ref: D. Lai, et al, Tetrahedron, 2011, 67, 6018

HO O OH

HO

735 Sinulariolone 4,7-Epoxy-3,8-dihydroxy-11-oxo-15(17)-cembren-16,12-olide Type: Cembrane diterpenoids. C20H30O6 Cryst. (Et2O), mp 215–216 °C, [α]D25 = −15.8° (c = 0.63, EtOH). Source: Soft corals Sinularia querciformis and Sinularia flexibilis (Philippines). Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L: inhibits up-regulation of pro-inflammatory COX-2 to 17.4% compare with control LPS-stimulated cells alone); cytotoxic (HeLa, Hep2, Doay, MCF7, all ED50S > 20 μg/mL). Ref: P. P. Guerrero, et al, JNP, 1995, 58, 1185│T. Wen, et al, JNP, 2008, 71, 1133│Y. Lu, et al, JNP, 2008, 71, 1754 O O

O HO

O OH

736 Sinulariolone 3-acetate 4,7-Epoxy-3-acetoxy-8-hydroxy-11-oxo-15(17)-cembren-16,12-olide Type: Cembrane diterpenoids. C22H32O7 Source: Soft corals Sinularia querciformis and Sinularia flexibilis. Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L: inhibits up-regulation of pro-inflammatory iNOS to 20.3% and COX-2 to 14.0% compare with control LPS-stimulated cells alone); cytotoxic (HeLa,

244

3 Diterpenoids

Hep2, Doay, MCF7, all ED50S > 20 μg/mL). Ref: P. P. Guerrero, et al, JNP, 1995, 58, 1185│Y. Lu, et al, JNP, 2008, 71, 1754 O O

O

O

O

HO

O

737 Sinulariol P Type: Cembrane diterpenoids. C19H30O3 Source: Soft coral Sinularia rigida (Sanya Bay, Hainan, China). Pharm: Antifoulant (bryozoan Bugula neritina). Ref: D. Lai, et al, Tetrahedron, 2011, 67, 6018

OH O 7E

HO

738 Sinulariol Z Type: Cembrane diterpenoids. C20H34O3 Source: Soft coral Sinularia rigida (Sanya Bay, Hainan, China). Pharm: Antifoulant (barnacle Balanus amphitriteand bryozoan Bugula neritina). Ref: D. Lai, et al, J. Agric. Food Chem., 2013, 61, 4585

HO O

OH

739 Sinularolide B Type: Cembrane diterpenoids. C20H28O5 Cryst., mp 137–138 °C, [α]D25 = −134.3° (c = 0.05, CHCl3). Source: Soft corals Sinularia gibberosa, Lobophytum crassum and Lobophytum durum. Pharm: Anti-inflammatory (LPS-stimulated murine RAW 264.7 macrophage cells, 10 μmol/L, inhibits up-regulation of pro-inflammatory iNOS to 0.9% and COX-2 to 63.7% compare with control LPS-stimulated cells alone, IC50
50 μg/mL). Ref: C. A. Ospina, et al, JNP, 2003, 66, 357; 2006, 69, 1721│M. T. Crimmins, et al, Org. Lett., 2010, 12, 5028 O

H 4

O

O

H 1

12

H O

15

O

814 Briarellin K Type: Eunicellane diterpenoids. C22H32O6 Oil, [α]D26 = −14.9° (c = 1.2, CHCl3). Source: Gorgonian Briareum polyanthes (Puerto Rico). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 = 15 μg/mL); antituberculosis (Mycobacterium

270

3 Diterpenoids

tuberculosis H37Rv, 6.25 μg/mL no significant inhibitory activity). Ref: C. A. Ospina, et al, JNP, 2003, 66, 357 O O

H O

H

OH

H O O

815 Briarellin K hydroperoxide Type: Eunicellane diterpenoids. C22H32O7 Oil, [α]D20 = −25.6° (c = 1, CHCl3). Source: Gorgonian Briareum polyanthes (Puerto Rico). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 = 9 μg/mL). Ref: C. A. Ospina, et al, JNP, 2003, 66, 357 O O

H O

4

O

H 1

9

OH

12 11

H O

15

O

816 Briarellin L Type: Eunicellane diterpenoids. C26H38O7 Oil, [α]D26 = −20.8° (c = 1.2, CHCl3). Source: Gorgonian Briareum polyanthes (Puerto Rico). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 = 8 μg/mL). Ref: C. A. Ospina, et al, JNP, 2003, 66, 357 O O

H

4

O

H 1

12 11

H

O 9

O

O

15

O

817 Briarellin M Type: Eunicellane diterpenoids. C22H34O7 Oil, [α]D26 = −14.5° (c = 1, CHCl3). Source: Gorgonian Briareum polyanthes (Puerto Rico). Pharm: Antiplasmodial (Plasmodium

3.15 Eunicellane diterpenoids

271

falciparum, IC50 = 22 μg/mL). Ref: C. A. Ospina, et al, JNP, 2003, 66, 357; 2006, 69, 1721 H

O 4

O

H

O

8

1

OH OH

12

H O

15

O

818 Briarellin N Type: Eunicellane diterpenoids. C23H36O7 Oil, [α]D26 = −13.6° (c = 1.1, CHCl3). Source: Gorgonian Briareum polyanthes (Puerto Rico). Pharm: Antituberculosis (Mycobacterium tuberculosis H37Rv, 6.25 μg/mL no significant inhibitory activity). Ref: C. A. Ospina, et al, JNP, 2003, 66, 357; 2006, 69, 1721 H

O 4

1

8

O

H

O

OH O

12

H O

15

O

819 Briarellin O Type: Eunicellane diterpenoids. C24H38O7 Oil, [α]D26 = −24.4° (c = 1.1, CHCl3). Source: Gorgonian Briareum polyanthes (Puerto Rico). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 = 24 μg/mL). Ref: C. A. Ospina, et al, JNP, 2003, 66, 357; 2006, 69, 1721 O O H

OH

H

O

8 9

OH

H O O

820 seco-Briarellinone Type: Eunicellane diterpenoids. C20H28O6 Colorless oil, [α]D20 = +38.1° (c = 0.4, CHCl3). Source: Gorgonian Briareum asbestinum (Bocas del Toro, Caribbean Sea, Panama). Pharm: Anti-inflammatory (NO production inhibitor, LPS-stimulated macrophages, IC50 = 4.7 μmol/L). Ref: J. F. Gómez-Reyes, et al, Mar. Drugs, 2012, 10, 2608

272

O

HO

3 Diterpenoids

H H O

H

O

HH

O

O H

821 Briarellin P Type: Eunicellane diterpenoids. C25H40O7 Oil, [α]D26 = −8.8° (c = 1.1, CHCl3). Source: Gorgonian Briareum polyanthes (Puerto Rico). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 = 14 μg/mL). Ref: C. A. Ospina, et al, JNP, 2003, 66, 357; 2006, 69, 1721 H

O

OH

4

O

H

O 1

8

O

12

H O

15

O

822 Briarellin S Type: Eunicellane diterpenoids. C28H44O7 Colorless oil, [α]D20 = +36.1° (c = 4.1, CHCl3). Source: Gorgonian Briareum asbestinum (Bocas del Toro, Caribbean Sea, Panama). Pharm: Anti-inflammatory (NO production inhibitor, LPS-stimulated macrophages, IC50 = 20.3 μmol/L). Ref: J. F. Gómez-Reyes, et al, Mar. Drugs, 2012, 10, 2608 O

HO

H O

H

OH

H

O O

O

6

823 Calicophirin A Type: Eunicellane diterpenoids. C26H38O8 Colorless oil, [α]D25 = −75.7° (c = 0.8, CHCl3), [α]D19 = −92.3° (c = 0.37, CHCl3). Source: Gorgonians Muricella sp. (Korea waters), Calicogorgia sp. and Astrogorgia sp. (Beibuwan Bay, Guangxi, China). Pharm: Cytotoxic (K562, LC50 = 0.9 μg/mL); PLA2 inhibitor (50 μg/mL, InRt = 42%); insecticide; antifoulant (barnacle Balanus Amphitrite, EC50 > 25 μg/mL). Ref: M. Ochi, et al, Heterocycles, 1991, 32, 19│Y. Seo, et al, NPL, 2000, 14, 197│D. Lai, et al, JNP, 2012, 75, 1595

3.15 Eunicellane diterpenoids

O

273

H

O

O O

O

H O O

O

824 Calicophirin B Type: Eunicellane diterpenoids. C24H36O5 Oil, [α]D19 = −106° (c = 0.46, CHCl3). Source: Gorgonians Calicogorgia sp., Muricella sp. and Astrogorgia sp. (Beibuwan Bay, Guangxi, China). Pharm: Insecticide; cytotoxic; cAMP phosphodiesterase inhibitor; anti-inflammatory. Ref: M. Ochi, et al, Heterocycles, 1991, 32, 19│Y. Seo, et al, JNP, 1997, 60, 171│Y. -H. Park, et al, Yakhak Hoechi, 1997, 41, 345│P. Bernardelli, et al, Heterocycles, 1998, 49, 531│D. Lai, et al, JNP, 2012, 75, 1595 H O O

O

H O O

825 Cladiella peroxide Type: Eunicellane diterpenoids. C20H32O4 [α]D23 = −27.8° (c = 0.42, CHCl3). Source: Soft coral Cladiella shaeroides (Japan waters). Pharm: Toxic (brine shrimp). Ref: K. Yamada, et al, JNP, 1997, 60, 393 H

O O

OH

H OH

826 Cladiellin Type: Eunicellane diterpenoids. C22H34O3 Source: Soft corals Cladiella pachyclados (Red Sea) and Cladiella spp. Pharm: Anti-migration (wound-healing assay, PC3, 50 μmol/L, migration ≈ 52%, moderate, control 4-Hydroxyphenylmethylene hydantoin, 200 μmol/L, migration ≈ 25%); anti-inflammatory; cAMP phosphodiesterase inhibitor; toxic (brine shrimp). Ref: R. Kazlauskas, et al, Tet. Lett., 1977, 4643│P. Bernardelli, et al, J. Am. Chem. Soc. 2001, 123, 9021│H. M. Hassan, et al, JNP, 2010, 73, 848

274

3 Diterpenoids

H z

O H

O O

827 Cladiellisin 6,13-Epoxy-4(18),8(19)-eunicelladiene-9,12-diol Type: Eunicellane diterpenoids. C20H32O3 Cryst., mp 215 °C, [α]D23 = −21.3° (c = 0.51, CHCl3), [α]D26 = +90° (c = 0.3, CHCl3). Source: Soft corals Cladiella sphaeroides, Cladiella australis (Andaman and Nicobar Is., Indian Ocean) and Cladiella similis, sea pen Virgularia juncea. Pharm: Cytotoxic (P388, ED50 = 2.0 μg/mL). Ref: J. Liu, et al, Chinese Sci. Bull., 1992, 37, 1627│C. B. Rao, et al, JNP, 1994, 57, 574│D. S. Rao, et al, Indian J. Chem., Sect. B, 1994, 33, 198│K. Yamada, et al, JNP, 1997, 60, 393│S. P. Chen, et al, JNP, 2001, 64, 1241 H OH O H OH

828 Cladielloide B Type: Eunicellane diterpenoids. C26H40O7 Source: Soft coral Cladiella sp. (Indonesia). Pharm: Cytotoxic (potent); superoxide inhibitor; elastase inhibitor. Ref: Y. -H. Chen, et al, Mar. Drugs, 2010, 8, 2936│Y. -H. Chen, et al, Mar. Drugs, 2011, 9, 934 (structure revised) H

H OH

2R

O

O

9R

H

H

OH O O O

829 Cladieunicellin A Type: Eunicellane diterpenoids. C20H32O3 Colorless oil, [α]D23 = −10° (c = 0.51, CHCl3). Source: Soft coral Cladiella sp. (Indonesia). Pharm: Cytotoxic (DLD-1, IC50 = 26.5 μg/mL, control Doxorubicin, IC50 = 0.09 μg/mL; HL60, IC50 > 40 μg/mL, Doxorubicin, IC50 = 0.03 μg/mL; CCRF-CEM, IC50 > 40 μg/mL, Doxorubicin, IC50 = 0.18 μg/mL; P388D1, IC50 > 40 μg/mL, Doxorubicin, IC50 = 0.11 μg/mL); anti-

3.15 Eunicellane diterpenoids

275

inflammatory (hmn Neutrophils in response to fMLP/CB: superoxide anion O2•− generation inhibitor, 10 μg/mL, InRt = (22.8 ± 6.3)%); control DPI, IC50 = (0.8 ± 0.2) μg/mL; elastase release inhibitor, 10 μg/mL, InRt = (25.9 ± 6.7)%, control Elastatinal, IC50 = (30.8 ± 5.7)μg/mL). Ref: Y. -H. Chen, et al, CPB, 2011, 59, 353 H

H OH O

H H

OH

830 Cladieunicellin B Type: Eunicellane diterpenoids. C20H32O4 Colorless oil, [α]D23 = −47° (c = 0.07, CHCl3). Source: Soft coral Cladiella sp. (Indonesia). Pharm: Cytotoxic (DLD-1, IC50 = 2.0 μg/mL, control Doxorubicin, IC50 = 0.09 μg/mL; HL60, IC50 > 40 μg/mL, Doxorubicin, IC50 = 0.03 μg/mL; CCRF-CEM, IC50 > 40 μg/mL, Doxorubicin, IC50 = 0.18 μg/mL; P388D1, IC50 > 40 μg/mL, Doxorubicin, IC50 = 0.11 μg/mL). Ref: Y. -H. Chen, et al, CPB, 2011, 59, 353 H

H OH O

H H

OH OH

831 Cladieunicellin C Type: Eunicellane diterpenoids. C22H34O5 Colorless oil, [α]D23 = −29° (c = 0.07, CHCl3). Source: Soft coral Cladiella sp. (Indonesia). Pharm: Cytotoxic (DLD-1, IC50 > 40 μg/mL, control Doxorubicin, IC50 = 0.09 μg/mL; HL60, IC50 = 18.4 μg/mL, Doxorubicin, IC50 = 0.03 μg/mL; CCRF-CEM, IC50 > 40 μg/mL, Doxorubicin, IC50 = 0.18 μg/mL; P388D1, IC50 > 40 μg/mL, Doxorubicin, IC50 = 0.11 μg/mL); anti-inflammatory (Hmn Neutrophils in Response to fMLP/CB: superoxide anion O2•− generation inhibitor, IC50 = (8.1 ± 0.3)%); control DPI, IC50 = (0.8 ± 0.2)μg/mL; elastase release inhibitor, 10 μg/mL, InRt = (49.4 ± 6.2)%, control Elastatinal, IC50 = (30.8 ± 5.7)μg/mL). Ref: Y. -H. Chen, et al, CPB, 2011, 59, 353 O

H

H OH O

H

H

O O

276

3 Diterpenoids

832 Cladieunicellin D Type: Eunicellane diterpenoids. C20H32O5 Colorless oil, [α]D23 = −5° (c = 0.06, CHCl3). Source: Soft coral Cladiella sp. (Indonesia). Pharm: Anti-inflammatory (hmn neutrophils in response to fMLP/CB: superoxide anion O2•− generation inhibitor, 10 μg/mL, InRt = (41.7 ± 6.2)%); control DPI, IC50 = (0.8 ± 0.2)μg/mL; elastase release inhibitor, 10 μg/mL, InRt = (48.2 ± 7.0)%, control Elastatinal, IC50 = (30.8 ± 5.7)μg/mL). Ref: Y. -H. Chen, et al, CPB, 2011, 59, 353 H

H

OH O O

H

H

OH OH

833 Cladieunicellin E Type: Eunicellane diterpenoids. C22H36O6 Colorless oil, [α]D23 = +10° (c = 0.13, CHCl3). Source: Soft coral Cladiella sp. (Indonesia). Pharm: Cytotoxic (DLD-1, IC50 > 40 μg/mL, control Doxorubicin, IC50 = 0.09 μg/mL; HL60, IC50 = 2.7 μg/mL, Doxorubicin, IC50 = 0.03 μg/mL; CCRF-CEM, IC50 = 31.1 μg/mL, Doxorubicin, IC50 = 0.18 μg/mL; P388D1, IC50 > 40 μg/mL, Doxorubicin, IC50 = 0.11 μg/mL); anti-inflammatory (Hmn Neutrophils in Response to fMLP/CB: superoxide anion O2•− generation inhibitor, 10 μg/mL, InRt = (36.9 ± 5.2)%); control DPI, IC50 = (0.8 ± 0.2)μg/mL; elastase release inhibitor, 10 μg/mL, InRt = (12.7 ± 7.3)%, control Elastatinal, IC50 = (30.8 ± 5.7)μg/mL). Ref: Y. -H. Chen, et al, CPB, 2011, 59, 353 O

H

H

OH O O

O H

H

OH

834 Cladieunicellin F Type: Eunicellane diterpenoids. C20H34O3 Colorless oil, [α]D23 = –194° (c = 0.07, CHCl3). Source: Soft coral Cladiella sp. (Indonesia). Pharm: Anti-inflammatory (superoxide anion O2•− generation inhibitor, 10 μg/mL, InRt = (6.46 ± 1.28)%); elastase release inhibitor (10 μg/mL, InRt = (12.91 ± 3.56)%). Ref: Y. -H. Chen, et al, Mar. Drugs, 2011, 9, 934

3.15 Eunicellane diterpenoids

HO

H

277

OH

H O

835 Cladieunicellin L Type: Eunicellane diterpenoids. C26H40O9 Source: Soft coral Cladiella sp. (Taiwan water). Pharm: Cytotoxic (Molt4, IC50 = 14.42 μmol/L, control Doxorubicin, IC50 = 0.02 μmol/L; HL60, IC50 > 20 μmol/L; Doxorubicin, IC50 = 0.02 μmol/L). Ref: T. -H. Chen, et al, Mar. Drugs, 2014, 12, 2144 O H

O

OH

H

OH O

O H

H

H

O O O

836 Cladieunicellin M Type: Eunicellane diterpenoids. C28H44O9 Source: Soft coral Cladiella sp. (Taiwan water). Pharm: Cytotoxic (Molt4, IC50 = 16.43 μmol/L, control Doxorubicin, IC50 = 0.02 μmol/L; HL60, IC50 > 20 μmol/L; Doxorubicin, IC50 = 0.02 μmol/L). Ref: T. -H. Chen, et al, Mar. Drugs, 2014, 12, 2144 H

H

OH

OH O

O O H O

H

H

O O

O

837 Cladieunicellin N Klymollin Q Type: Eunicellane diterpenoids. C24H38O7 Source: Soft corals Cladiella sp. and Klyxum molle. Pharm: Cytotoxic (Molt4, IC50 > 20 μmol/L, control Doxorubicin, IC50 = 0.02 μmol/L; HL60, IC50 > 20 μmol/L; Doxorubicin, IC50 = 0.02 μmol/L). Ref: M. C. Lin, et al, JNP, 2013, 76, 1661│T. -H. Chen, et al, Mar. Drugs, 2014, 12, 2144

278

3 Diterpenoids

H

HO

OH 7

O

O

O O

H

O

838 Cladieunicellin O Type: Eunicellane diterpenoids. C26H40O8 Source: Soft coral Cladiella sp. (Taiwan water). Pharm: Cytotoxic (Molt4, IC50 = 14.17 μmol/L, control Doxorubicin, IC50 = 0.02 μmol/L; HL60, IC50 > 20 μmol/L; Doxorubicin, IC50 = 0.02 μmol/L). Ref: T. -H. Chen, et al, Mar. Drugs, 2014, 12, 2144 O H H

O

OH O O

H

O

H H

O O

839 Cladieunicellin P Type: Eunicellane diterpenoids. C28H44O9 Source: Soft coral Cladiella sp. (Taiwan water). Pharm: Cytotoxic (Molt4, IC50 > 20 μmol/L, control Doxorubicin, IC50 = 0.02 μmol/L; HL60, IC50 > 20 μmol/L; Doxorubicin, IC50 = 0.02 μmol/L). Ref: T. -H. Chen, et al, Mar. Drugs, 2014, 12, 2144 O H

O

H

OH

OH O

O H

H

H

O O O

840 Cladieunicellin Q Type: Eunicellane diterpenoids. C24H38O7 Source: Soft coral Cladiella sp. (Taiwan water). Pharm: Cytotoxic (Molt4, IC50 = 15.55 μmol/L, control Doxorubicin, IC50 = 0.02 μmol/L; HL60, IC50 > 20 μmol/L; Doxorubicin, IC50 = 0.02 μmol/L). Ref: T. -H. Chen, et al, Mar. Drugs, 2014, 12, 2144

3.15 Eunicellane diterpenoids

H

H

OH

279

OH O

O O H

H

H

O O

841 14-Deacetoxycalicophirin B 6,13-Epoxy-12-acetoxy-3,8-eunicelladiene Type: Eunicellane diterpenoids. C22H34O3 white solid, mp 78–79 °C, [α]D25 = −34.7° (c = 0.5, CHCl3). Source: Gorgonians Muricella sp. (Korea waters) and Astrogorgia sp. (Beibuwan Bay, Guangxi, China). Pharm: Cytotoxic (A549, ED50 = 12.7 μg/mL, SK-OV-3, ED50 = 21.3 μg/mL, SK-MEL-2, ED50 = 11.6 μg/mL, HCT15, ED50 = 13.9 μg/mL); antifoulant (barnacle Balanus Amphitrite, EC50 = 0.59 μg/mL); LD50 = 0.3 ppm. Ref: Y. Seo, et al, JNP, 1997, 60, 171│D. Lai, et al, JNP, 2012, 75, 1595 H O H

O O

842 (4β,6α,8Z,13α)-4,12-Diacetoxy-6,13-epoxy-8-eunicellene Type: Eunicellane diterpenoids. C24H38O5 Oil, [α]D = −15.6° (c = 1.4, CHCl3). Source: Gorgonian Eunicella cavolini (Mediterranean Sea). Pharm: Toxic (fish and brine shrimp). Ref: S. De Rosa, et al, NPL, 1995, 7, 259 O

O

H O H O O

843 3,6-Diacetylcladiellisin Type: Eunicellane diterpenoids. C24H36O4 Source: Soft coral Cladiella pachyclados (Red Sea). Pharm: Anti-migration (wound-healing assay, PC3, 50 μmol/L, migration ≈ 38%, potent, control 4-Hydroxyphenylmethylene hydantoin, 200 μmol/L, migration ≈ 25%). Ref: H. M. Hassan, et al, JNP, 2010, 73, 848

280

3 Diterpenoids

H

O O O

O

H

O

844 Dihydrovaldivone A Type: Eunicellane diterpenoids. C25H36O5 Oil. Source: Soft coral Alcyonium valdivae (South Africa). Pharm: Anti-inflammatory; phosphatidase A2 inhibitor. Ref: Y. Lin, et al, Tetrahedron, 1993, 49, 7977 O O

H

O O

H

OH

845 Eleutherobin Type: Eunicellane diterpenoids. C35H48N2O10 Amorph. solid, [α]D25 = −49.3° (c = 3, MeOH). Source: Soft corals Eleutherobia cf. albiflora and Nephthea chabroli, gorgonian Erythropodium caribaeorum. Pharm: Cytotoxic (with microtubule stabilising props, shows potent antitumour activity, underwent preclinical evaluation as anticancer drug (2001), but is no longer being pursued due to lack of material availability). Ref: T. Lindel, et al, JACS, 1997, 119, 8744│B. H. Long, et al, Cancer Res., 1998, 58, 1111│US Pat., 1995, 5 473 057; CA, 124, 194297 O N

O H

N O

H

O OO O

HO OH

O

846 Eleuthoside A Type: Eunicellane diterpenoids. C36H48N2O11 Oil, [α]D = −9° (c = 0.2, CHCl3). Source: Soft coral Eleutherobia aurea (South Africa). Pharm: Tubulin polym. induction

3.15 Eunicellane diterpenoids

281

inhibitor; cytotoxic (strong), antineoplastic. Ref: S. Ketzinel, et al, JNP, 1996, 59, 873│K. C. Nicolaou, et al, JACS, 1998, 120, 8661; 8674 O N

O H

N O

H

OH OO O

HO

O

O O

847 Hirsutalin A Type: Eunicellane diterpenoids. C28H44O7 Colorless oil; [α]D25 = −22° (c = 0.26, CHCl3). Source: Soft coral Cladiella hirsuta (Sianglu Islet, Penghu Is., Taiwan). Pharm: Cytotoxic (Hep3B, IC50 = 29 μmol/L, control Doxorubicin, IC50 = 1.3 μmol/L; A549, IC50 = 28 μmol/L, Doxorubicin, IC50 = 2.6 μmol/L; Ca9-22, IC50 = 35 μmol/L, Doxorubicin, IC50 = 0.2 μmol/L). Ref: B. -W. Chen, et al, JNP, 2010, 73, 1785 H

H

O

OH O

H

O O HO

O

848 Hirsutalin B Type: Eunicellane diterpenoids. C30H46O9 Colorless oil; [α]D25 = −41° (c = 0.81, CHCl3). Source: Soft coral Cladiella hirsuta (Sianglu Islet, Penghu Is., Taiwan). Pharm: Anti-inflammatory (10 μmol/L, reduces level of iNOS protein to (6.8 ± 0.6)% relative to control cells stimulated with LPS only); anti-inflammatory (10 μmol/L, reduces COX-2 expression = (49.0 ± 2.3)% relative to control cells by LPS treatment). Ref: B. -W. Chen, et al, JNP, 2010, 73, 1785

282

3 Diterpenoids

H

OH O

H

O

H

OH O O

O

O O

849 Hirsutalin C Type: Eunicellane diterpenoids. C28H44O7 Colorless oil; [α]D25 = −78° (c = 0.37, CHCl3). Source: Soft coral Cladiella hirsuta (Sianglu Islet, Penghu Is., Taiwan). Pharm: Anti-inflammatory (10 μmol/L, reduces level of iNOS protein to (43.6 ± 8.7)% relative to control cells stimulated with LPS only). Ref: B. -W. Chen, et al, JNP, 2010, 73, 1785 H

OH O

H H OH

O O O O

850 Hirsutalin D Type: Eunicellane diterpenoids. C26H40O7 Colorless oil; [α]D22 = −52° (c = 0.15, CHCl3). Source: Soft coral Cladiella hirsuta (Sianglu Islet, Penghu Is., Taiwan). Pharm: Anti-inflammatory (10 μmol/L, reduces level of iNOS protein to (3.3 ± 0.1)% relative to control cells stimulated with LPS only). Ref: B. -W. Chen, et al, JNP, 2010, 73, 1785 H

H OH

OH O

H

O O O O

851 Hirsutalin E Type: Eunicellane diterpenoids. C24H40O5 Colorless oil; [α]D22 = −13° (c = 3.18, CHCl3). Source: Soft coral Cladiella hirsuta (Sianglu Islet, Penghu Is., Taiwan), soft coral Cladiella hirsuta (depth of 10 m, off coast of Sianglu Islet (23°32‘ N, 119°38‘ E),

3.15 Eunicellane diterpenoids

283

Penghu Islands, Taiwan, in June 2008). Pharm: Cytotoxic (P388, IC50 > 40 μmol/L, control 5-FU, IC50 = 8.5 μmol/L; K562, IC50 > 40 μmol/L, 5-FU, IC50 = 24.6 μmol/L; HT29, IC50 > 40 μmol/L, 5-FU, IC50 = 20.8 μmol/L; A549, IC50 = 37.2 μmol/L; 5-FU, IC50 = 38.5 μmol/L) (Huang, 2014); anti-inflammatory (inhibitor of superoxide anion generation, 10 μmol/L, InRt = (4.2 ± 3.8)%, IC50 > 10 μmol/L) (Huang, 2014); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μmol/L, InRt = (3.1 ± 6.9)%, IC50 > 10 μmol/L) (Huang, 2014); cytotoxic (Hep3B, IC50 = 14 μmol/L, control Doxorubicin, IC50 = 1.3 μmol/L; MDA-MB-231, IC50 = 41 μmol/L, Doxorubicin, IC50 = 2.0 μmol/L; MCF7, IC50 = 35 μmol/L, Doxorubicin, IC50 = 2.9 μmol/L; A549, IC50 = 34 μmol/L, Doxorubicin, IC50 = 2.6 μmol/L; Ca9-22, IC50 = 34 μmol/L, Doxorubicin, IC50 = 0.2 μmol/L; HepG2, IC50 = 4.7 μmol/L, Doxorubicin, IC50 = 0.4 μmol/L) (Chen, 2010). Ref: B. -W. Chen, et al, JNP, 2010, 73, 1785│T. -Z. Huang, et al, Mar. Drugs, 2014, 12, 2446 OH

H

OH O O

H O

852 Hirsutalin F Type: Eunicellane diterpenoids. C28H44O8 Colorless oil; [α]D22 = −62° (c = 0.10, CHCl3). Source: Soft coral Cladiella hirsuta (Sianglu Islet, Penghu Is., Taiwan). Pharm: Cytotoxic (HepG2, IC50 = 29 μmol/L, control Doxorubicin, IC50 = 0.4 μmol/L; Hep3B, IC50 = 29 μmol/L, Doxorubicin, IC50 = 1.3 μmol/L; MCF7, IC50 = 32 μmol/L, Doxorubicin, IC50 = 2.9 μmol/L). Ref: B. -W. Chen, et al, JNP, 2010, 73, 1785 O

OH

H

H

O

H

OH

O O O O

853 Hirsutalin H Type: Eunicellane diterpenoids. C26H42O7 Colorless oil; [α]D22 = −140° (c = 0.30, CHCl3). Source: Soft coral Cladiella hirsuta (Sianglu Islet, Penghu Is., Taiwan). Pharm: Anti-inflammatory (10 μmol/L, reduces level of iNOS protein to (32.3 ± 6.1)% relative to control cells stimulated with LPS only). Ref: B. -W. Chen, et al, JNP, 2010, 73, 1785

284

3 Diterpenoids

OH OH

H H

O O

H

O

O

O

854 Hirsutalin I Type: Eunicellane diterpenoids. C26H42O8 Colorless oil, [α]D22 = −21° (c = 0.14, CHCl3). Source: Soft coral Cladiella hirsuta (Sianglu Islet, Penghu Is., Taiwan). Pharm: NO production inhibitor (stimulated macrophages, 20 μg/mL, InRt = 10%, weak). Ref: B. -W. Chen, et al, Tetrahedron, 2013, 69, 2296 O H

O O

H

OH O

H

H

HO

H O O

855 Hirsutalin J Type: Eunicellane diterpenoids. C28H44O8 Colorless oil, [α]D22 = +13° (c = 0.58, CHCl3). Source: Soft coral Cladiella hirsuta (Sianglu Islet, Penghu Is., Taiwan). Pharm: NO production inhibitor (stimulated macrophages, 20 μg/mL, InRt = 20%, weak). Ref: B. -W. Chen, et al, Tetrahedron, 2013, 69, 2296 H

H OH O

H HO

H

H

O OH O O O

856 Hirsutalin K Type: Eunicellane diterpenoids. C24H36O7 Colorless oil, [α]D22 = +17° (c = 0.18, CHCl3). Source: Soft coral Cladiella hirsuta (Sianglu Islet, Penghu Is., Taiwan). Pharm: NO production inhibitor (stimulated macrophages, 20 μg/mL, InRt = 97%, IC50 = 9.8 μg/mL, moderate). Ref: B. -W. Chen, et al, Tetrahedron, 2013, 69, 2296

3.15 Eunicellane diterpenoids

O

O

285

OH

H

O O H H

O O

857 Hirsutalin L Type: Eunicellane diterpenoids. C28H44O8 Colorless oil, [α]D22 = −44° (c = 0.11, CHCl3). Source: Soft coral Cladiella hirsuta (Sianglu Islet, Penghu Is., Taiwan). Pharm: NO production inhibitor (stimulated macrophages, 20 μg/mL, InRt = 20%, weak). Ref: B. -W. Chen, et al, Tetrahedron, 2013, 69, 2296 H

OH

H

OH O

O O

H H

O

OH

O

858 Hirsutalin M Type: Eunicellane diterpenoids. C24H38O6 Colorless oil, [α]D22 = −29° (c = 0.16, CHCl3). Source: Soft coral Cladiella hirsuta (Sianglu Islet, Penghu Is., Taiwan). Pharm: NO production inhibitor (stimulated macrophages, 20 μg/mL, InRt = 15%, weak). Ref: B. -W. Chen, et al, Tetrahedron, 2013, 69, 2296 H

H OH O

HO

H

H H

OH O O

859 Hirsutalin N Type: Eunicellane diterpenoids. C24H38O7 Colorless oil, [α]D25 = −98° (c = 0.54, CHCl3). Source: Soft coral Cladiella hirsuta (depth of 10 m, off coast of Sianglu Islet (23°32’ N, 119°38’ E), Penghu Islands, Taiwan, in June 2008). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μmol/L, InRt = (1.0 ± 5.5)%, IC50 > 10 μmol/L, p < 0.001); anti-inflammatory (elastase release inhibitor, fMLP/CBinduced hmn neutrophils, 10 μmol/L, InRt = (31.7 ± 3.2)%, IC50 > 10 μmol/L, p < 0.001). Ref: T. -Z. Huang, et al, Mar. Drugs, 2014, 12, 2446

286

3 Diterpenoids

O O

OH

O H O

H

H O

H O

860 Hirsutalin O Type: Eunicellane diterpenoids. C24H38O6 Colorless oil, [α] D25 = −128° (c = 0.68, CHCl3). Source: Soft coral Cladiella hirsuta (depth of 10 m, off coast of Sianglu Islet (23°32’ N, 119°38’ E), Penghu Islands, Taiwan, in June 2008). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μmol/L, InRt = (9.6 ± 5.5)%, IC50 > 10 μmol/L); anti-inflammatory (elastase release inhibitor, fMLP/CBinduced hmn neutrophils, 10 μmol/L, InRt = (11.5 ± 5.0)%, IC50 > 10 μmol/L). Ref: T. -Z. Huang, et al, Mar. Drugs, 2014, 12, 2446 O O

H

H O O

H

H

O OH

861 Hirsutalin P Type: Eunicellane diterpenoids. C23H40O6 Colorless oil, [α]D25 = +27° (c = 0.54, CHCl3). Source: Soft coral Cladiella hirsuta (depth of 10 m, off coast of Sianglu Islet (23°32’ N, 119°38’ E), Penghu Islands, Taiwan, in June 2008). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μmol/L, InRt = (1.7 ± 0.7)%, IC50 > 10 μmol/L, p < 0.05); anti-inflammatory (elastase release inhibitor, fMLP/CBinduced hmn neutrophils, 10 μmol/L, InRt = (17.9 ± 6.9)%, IC50 > 10 μmol/L, p < 0.05). Ref: T. -Z. Huang, et al, Mar. Drugs, 2014, 12, 2446 O O

H

OH

H

O O H

H

OH

862 Hirsutalin Q Type: Eunicellane diterpenoids. C22H36O5 Colorless oil, [α]D25 = +12° (c = 0.51, CHCl3). Source: Soft coral Cladiella hirsuta (depth of 10 m, off coast of Sianglu

3.15 Eunicellane diterpenoids

287

Islet (23°32’ N, 119°38’ E), Penghu Islands, Taiwan, in June 2008). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μmol/L, InRt = (6.1 ± 2.6)%, IC50 > 10 μmol/L); anti-inflammatory (elastase release inhibitor, fMLP/CBinduced hmn neutrophils, 10 μmol/L, InRt = (6.4 ± 2.4)%, IC50 > 10 μmol/L). Ref: T. -Z. Huang, et al, Mar. Drugs, 2014, 12, 2446 O O

H

H OH O

H

H

OH

863 Hirsutalin R Type: Eunicellane diterpenoids. C28H42O7 Yellow oil, [α]D25 = +18° (c = 0.54, CHCl3). Source: Soft coral Cladiella hirsuta (depth of 10 m, off coast of Sianglu Islet (23°32’ N, 119°38’ E), Penghu Islands, Taiwan, in June 2008). Pharm: Cytotoxic (P388, IC50 = 13.8 μmol/L, control 5-FU, IC50 = 8.5 μmol/L; K562, IC50 = 36.3 μmol/L, 5-FU, IC50 = 24.6 μmol/L; HT29, IC50 > 40 μmol/L, 5-FU, IC50 = 20.8 μmol/L; A549, IC50 > 40 μmol/L; 5-FU, IC50 = 38.5 μmol/L); anti-inflammatory (inhibitor of superoxide anion generation, 10 μmol/L, InRt = (6.5 ± 2.9)%, IC50 > 10 μmol/L, p < 0.05); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μmol/L, InRt = (13.6 ± 4.9)%, IC50 > 10 μmol/L, p < 0.05). Ref: T. -Z. Huang, et al, Mar. Drugs, 2014, 12, 2446 H H

O O

H

O

H H O

OH

O O

864 (–)-6α-Hydroxypolyanthellin A Type: Eunicellane diterpenoids. C22H36O5 Source: Soft coral Cladiella krempfi (Kavaratti I., Lakshadweep Is. India). Pharm: Antifoulant (barnacle, moderate). Ref: V. P. L. Mol, et al, Can. J. Chem., 2011, 89, 57 O

H

O

OH O

H

O

288

3 Diterpenoids

865 Klymollin C Type: Eunicellane diterpenoids. C26H38O9 Colorless oil. Source: Soft coral Klyxum molle (Penghu Is., Taiwan). Pharm: Anti-inflammatory (Inhibits expression of proinflammatory proteins iNOS and COX-2 in LPS-stimulated RAW264.7 macrophages). Ref: F. -J. Hsu, et al, JNP, 2011, 74, 2467 O O O

H OH O

O

H O

O O

866 Klymollin D Type: Eunicellane diterpenoids. C24H36O7 Colorless oil. Source: Soft coral Klyxum molle (Penghu Is., Taiwan). Pharm: Anti-inflammatory (Inhibits expression of proinflammatory proteins iNOS and COX-2 in LPS-stimulated RAW264.7 macrophages). Ref: F. -J. Hsu, et al, JNP, 2011, 74, 2467 O O

H OH O

O H

O O

867 Klymollin E Type: Eunicellane diterpenoids. C28H42O11 Source: Soft coral Klyxum molle (Penghu Is., Taiwan). Pharm: Anti-inflammatory (inhibits expression of pro-inflammatory iNOS protein in LPS-stimulated RAW264.7 macrophages). Ref: F. -J. Hsu, et al, JNP, 2011, 74, 2467 O O O O

OH

H

O

O O

H

O O O

868 Klymollin F Type: Eunicellane diterpenoids. C41H68O11 Colorless oil. Source: Soft coral Klyxum molle (Penghu Is., Taiwan). Pharm: Anti-inflammatory (Inhibits expression of proinflammatory proteins iNOS and COX-2 in LPS-stimulated RAW264.7 macrophages). Ref: F. -J. Hsu, et al, JNP, 2011, 74, 2467

3.15 Eunicellane diterpenoids

O O O

OH

H

O

O O

289

O

H

O

O

O

869 Klymollin G Type: Eunicellane diterpenoids. C43H72O11 Colorless oil. Source: Soft coral Klyxum molle (Penghu Is., Taiwan). Pharm: Anti-inflammatory (Inhibits expression of proinflammatory proteins iNOS and COX-2 in LPS-stimulated RAW264.7 macrophages). Ref: F. -J. Hsu, et al, JNP, 2011, 74, 2467

O O O

OH

H

O

O O

H

O

O O O

870 Klymollin H Type: Eunicellane diterpenoids. C27H40O11 Colorless oil. Source: Soft coral Klyxum molle (Penghu Is., Taiwan). Pharm: Anti-inflammatory (Inhibits expression of proinflammatory proteins iNOS and COX-2 in LPS-stimulated RAW264.7 macrophages). Ref: F. -J. Hsu, et al, JNP, 2011, 74, 2467 O O O O

OH

H

O

O O

H

H O O O

871 Klymollin W Type: Eunicellane diterpenoids. C24H38O6 Colorless oil, [α]D25 = +14° (c = 2.11, CHCl3). Source: Soft coral Klyxum molle (depth of 10 m, along coast of Penghu Islands, Taiwan, in June 2008). Pharm: Cytotoxic (MTT colorimetric method, CCRFCEM, ED50 = 9.6 μg/mL, Molt4, ED50 = 8.5 μg/mL, T47D, ED50 = 19.9 μg/mL, cell proliferation inhibitor). Ref: F. -Y. Chang, et al, Mar. Drugs, 2014, 12, 3060

290

3 Diterpenoids

H

H

OH O O

H

O

O

H

O

872 Klymollin X Type: Eunicellane diterpenoids. C24H38O6 Colorless oil, [α]D25 = +18° (c = 1.34, CHCl3). Source: Soft coral Klyxum molle (depth of 10 m, along coast of Penghu Islands, Taiwan, in June 2008). Pharm: Anti-inflammatory (IL-6 release inhibitor, LPS-induced mouse RAW264.7 macrophage cell line, significant). Ref: F. -Y. Chang, et al, Mar. Drugs, 2014, 12, 3060 OH

H H

O O O

H H

O

O

873 Klysimplexin B Type: Eunicellane diterpenoids. C26H40O7 Oil, [α]D22 = −42° (c = 0.11, CHCl3). Source: Soft coral Klyxum simplex (cultivated specimen, Dongsha Atoll, South China Sea). Pharm: Cytotoxic (HepG2, IC50 = 3.0 μg/mL; Hep3B, IC50 = 3.6 μg/mL; MDA-MB-231, IC50 = 6.9 μg/mL; MCF7, IC50 = 3.0 μg/mL; A549, IC50 = 2.0 μg/mL;Ca9-22, IC50 = 1.8 μg/mL). Ref: B. -W. Chen, et al, Tetrahedron, 2009, 65, 7016 O O

H

O

4 2

HO

9

O 12

H

O O

874 Klysimplexin G Type: Eunicellane diterpenoids. C24H40O7 Oil, [α]D22 = −54° (c = 0.23, CHCl3). Source: Soft corals Cladiella pachyclados (Red Sea) and Klyxum simplex (cultivated specimen, Dongsha Atoll, South China Sea). Pharm: Anti-migration (wound-healing assay, PC3, 50 μmol/L, migration ≈ 32%, potent, control 4-Hydroxyphenylmethylene hydantoin, 200 μmol/L, migration ≈ 25%); anti-invasive activity (Cultrex cell invasion assay, PC3, 10 μmol/L, invasion ≈ 48%, active, control 4-Mercaptoethylphenyl methylene

3.15 Eunicellane diterpenoids

291

hydantoin (S-Et-PMH), 50 μmol/L, invasion ≈ 50%). Ref: B. -W. Chen, et al, Tetrahedron, 2009, 65, 7016│H. M. Hassan, et al, JNP, 2010, 73, 848 O O

OH OH

H 8

4

9

O

2

12

H

O O

875 Klysimplexin H Type: Eunicellane diterpenoids. C30H48O9 Oil, [α]D22 = −74° (c = 0.1, CHCl3). Source: Soft coral Klyxum simplex. Pharm: Cytotoxic (HepG2, IC50 = 5.6 μg/mL; Hep3B, IC50 = 6.9 μg/mL; MDA-MB-231, IC50 = 4.4 μg/mL; MCF7, IC50 = 5.6 μg/mL; A549, IC50 = 2.8 μg/mL;Ca9-22, IC50 = 6.1 μg/mL). Ref: B. -W. Chen, et al, Tetrahedron, 2009, 65, 7016 O HO O

O

H

OH

8

4

9

O

2

12

O

H

O O

876 Klysimplexin J Type: Eunicellane diterpenoids. C42H74O8 Colorless oil, [α]D25 = −40° (c = 0.42, CHCl3). Source: Soft coral Klyxum simplex (cultured specimen). Pharm: Anti-inflammatory (RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 55%). Ref: B. -W. Chen, et al, Org. Biomol. Chem., 2011, 9, 834 O O

OH O

H

13

O

O

H O O

877 Klysimplexin K Type: Eunicellane diterpenoids. C44H78O8 Colorless oil, [α]D25 = −38° (c = 0.11, CHCl3). Source: Soft coral Klyxum simplex (cultured specimen). Pharm: Anti-inflammatory

292

3 Diterpenoids

(RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 35%). Ref: B. -W. Chen, et al, Org. Biomol. Chem., 2011, 9, 834 O O

OH O

H

15

O

O

H O O

878 Klysimplexin L Type: Eunicellane diterpenoids. C30H48O9 Colorless oil, [α]D25 = −64° (c = 0.12, CHCl3). Source: Soft coral Klyxum simplex (cultured specimen). Pharm: Anti-inflammatory (RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 25%). Ref: B. -W. Chen, et al, Org. Biomol. Chem., 2011, 9, 834 HO O O

H

OH O

O

H O

O

O

879 Klysimplexin M Type: Eunicellane diterpenoids. C30H48O10 Colorless oil, [α]D25 = −74° (c = 0.11, CHCl3). Source: Soft coral Klyxum simplex (cultured specimen). Pharm: Anti-inflammatory (RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 20%). Ref: B. -W. Chen, et al, Org. Biomol. Chem., 2011, 9, 834 HO O O O

OH

H

O O

O

H O O

880 Klysimplexin N Type: Eunicellane diterpenoids. C28H44O9 Colorless oil, [α]D25 = −53° (c = 0.10, CHCl3). Source: Soft coral Klyxum simplex (cultured specimen). Pharm: Anti-inflammatory (RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 35%). Ref: B. -W. Chen, et al, Org. Biomol. Chem., 2011, 9, 834

3.15 Eunicellane diterpenoids

HO O O

H

293

OH O

O

H O

O

O

881 Klysimplexin Q Type: Eunicellane diterpenoids. C28H36O3 Colorless oil, [α]D25 = +56° (c = 0.60, CHCl3). Source: Soft coral Klyxum simplex (cultured specimen). Pharm: Cytotoxic (HepG2, IC50 = 53.2 μmol/L; Hep3B, IC50 = 35.1 μmol/L; MDA-MB-231, IC50 = 44.0 μmol/L; MCF7, IC50 = 36.5 μmol/L; A549, IC50 = 40.5 μmol/L; Ca9-22, IC50 = 40.5 μmol/L). Ref: B. -W. Chen, et al, Org. Biomol. Chem., 2011, 9, 834 O O

H H

O

H

882 Klysimplexin R Type: Eunicellane diterpenoids. C20H34O Colorless oil, [α]D25 = +30° (c = 0.22, CHCl3). Source: Soft coral Klyxum simplex (cultured specimen). Pharm: Anti-inflammatory (RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 20%; inhibition of LPS induced upregulation of COX-2, inhibited COX-2 to ≈ 55%). Ref: B. -W. Chen, et al, Org. Biomol. Chem., 2011, 9, 834 HO

H

H

883 Klysimplexin S Type: Eunicellane diterpenoids. C26H42O7 Colorless oil, [α]D25 = −43° (c = 0.23, CHCl3). Source: Soft coral Klyxum simplex (cultured specimen). Pharm: Anti-inflammatory (RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 10%; inhibition of LPS induced upregulation of COX-2, inhibited COX-2to ≈ 40%). Ref: B. -W. Chen, et al, Org. Biomol. Chem., 2011, 9, 834

294

3 Diterpenoids

O

O

O

OH H

H

O

H

H O O

884 Klysimplexin sulfoxide A Type: Eunicellane diterpenoids. C27H46O6S Colorless oil, [α]D25 = −33° (c = 0.20, CHCl3). Source: Soft coral Klyxum simplex. Pharm: Anti-inflammatory (iNOS protein expression inhibitor in macrophages). Ref: B. -W. Chen, et al, Org. Biomol. Chem., 2010, 8, 2363 O O

S

H

O

O O

H

O

885 Klysimplexin sulfoxide B Type: Eunicellane diterpenoids. C31H52O9S Colorless oil, [α]D25 = −67° (c = 0.22, CHCl3). Source: Soft coral Klyxum simplex. Pharm: Anti-inflammatory (iNOS protein expression inhibitor in macrophages). Ref: B. -W. Chen, et al, Org. Biomol. Chem., 2010, 8, 2363 O

O O

HO O

S

H O

O

H

O O

886 Klysimplexin sulfoxide C Type: Eunicellane diterpenoids. C30H48O10S Source: Soft coral Klyxum simplex. Pharm: Anti-inflammatory (iNOS and COX-2 proteins expression inhibitor, in macrophages). Ref: B. -W. Chen, et al, Org. Biomol. Chem., 2010, 8, 2363

3.15 Eunicellane diterpenoids

O O S

HO

H

O

295

OH O

O

O

H

O

O

887 Klysimplexin T Type: Eunicellane diterpenoids. C22H36O4 Colorless oil, [α]D25 = −56° (c = 0.11, CHCl3). Source: Soft coral Klyxum simplex (cultured specimen). Pharm: Cytotoxic (HepG2, IC50 = 34.3 μmol/L; Hep3B, IC50 = 26.4 μmol/L; MDA-MB-231, IC50 = 44.0 μmol/L; MCF7, IC50 = 27.2 μmol/L; A549, IC50 = 42.0 μmol/L; Ca9-22, IC50 = 37.4 μmol/L). Ref: B. -W. Chen, et al, Org. Biomol. Chem., 2011, 9, 834 O HO

H

O

H

OH H

888 Krempfielin A Type: Eunicellane diterpenoids. C26H42O8 Colorless oil; [α]D25 = −39.2° (c = 0.83, CHCl3). Source: Soft coral Cladiella krempfi (Penghu Is., Taiwan). Pharm: Anti-inflammatory (immunoblot analysis assay, RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 93%). Ref: C. -J. Tai, et al, Mar. Drugs, 2011, 9, 2036

O

H

HO

OH OH

O

O H

O O

889 Krempfielin B Type: Eunicellane diterpenoids. C25H42O6 Colorless oil; [α]D25 = −62.9° (c = 0.35, CHCl3). Source: Soft coral Cladiella krempfi (Penghu Is., Taiwan). Pharm: Anti-inflammatory (immunoblot analysis assay, RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 38%, P < 0.05). Ref: C. -J. Tai, et al, Mar. Drugs, 2011, 9, 2036

296

3 Diterpenoids

H

HO

OH O

O H

O O

890 Krempfielin C Type: Eunicellane diterpenoids. C26H42O7 Colorless oil; [α]D25 = −51.3° (c = 0.62, CHCl3). Source: Soft coral Cladiella krempfi (Penghu Is., Taiwan), soft coral Cladiella sp. (Taiwan water). Pharm: Anti-inflammatory (immunoblot analysis assay, RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 55%, P < 0.05). Ref: C. -J. Tai, et al, Mar. Drugs, 2011, 9, 2036│T. -H. Chen, et al, Mar. Drugs, 2014, 12, 2144 H

HO

OH O

O

O H

O O

891 Krempfielin D Type: Eunicellane diterpenoids. C27H44O8 Colorless oil; [α]D25 = −52.4° (c = 0.50, CHCl3). Source: Soft coral Cladiella krempfi (Penghu Is., Taiwan). Pharm: Anti-inflammatory (immunoblot analysis assay, RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 62%, P < 0.05). Ref: C. -J. Tai, et al, Mar. Drugs, 2011, 9, 2036

O

H

HO

OH O

O

O H

O O

892 Krempfielin I Type: Eunicellane diterpenoids. C30H48O8 Colourless oil; [α]D25 = −18.3° (c = 0.35, CHCl3). Source: Soft Coral Cladiella krempfi (depth of 5–10 m, off coast of Penghu is.,Taiwan, Jun. 2008). Pharm: Cytotoxic (A549, ED50 = (15.0 ± 3.5)μg/mL, control Taxol, ED50 = (1.5 ± 0.9)μg/mL; BT-483, ED50 = (11.5 ± 1.8)μg/mL, Taxol, ED50 = (3.9 ± 0.8)μg/mL; H1299, ED50 = (19.2 ± 4.0)μg/mL, Taxol, ED50 = (1.2 ± 0.1)μg/mL; HepG2, ED50 = (12.9 ± 3.1)μg/mL, Taxol, ED50 = (1.4 ± 0.7)μg/mL; SAS, ED50 = (10.2 ±

3.15 Eunicellane diterpenoids

297

3.5)μg/mL, Taxol, ED50 = (2.3 ± 1.5)μg/mL; BEAS2B, ED50 > 20 μg/mL, Taxol, ED50 = (2.3 ± 1.5)μg/mL). Ref: C. J. Tai, et al, Mar. Drugs, 2013, 11, 788 O

H

H

O OH O O O

H

H

O O

893 Krempfielin J Type: Eunicellane diterpenoids. C23H38O5 Colorless oil, [α]D23 = +52° (c = 0.85, CHCl3). Source: Soft Coral Cladiella krempfi (depth of 5–10 m, off coast of Penghu is.,Taiwan, Jun. 2008). Pharm: Anti-inflammatory (10 μmol/L, elastase release inhibitor, fMLP/CB-induced hmn neutrophils, InRt = (14.92 ± 7.89)%, p < 0.05, IC50 > 10 μmol/L, control LY294002, IC50 = (4.12 ± 0.92)μmol/L). Ref: Y. N. Lee, et al, Mar. Drugs, 2013, 11, 2741 H

H

OH O O

H

H

O O

894 Krempfielin K Type: Eunicellane diterpenoids. C26H42O8 White powder, mp 162–163 °C, [α]D25 = −58° (c = 1.5, CHCl3). Source: Soft Coral Cladiella krempfi (depth of 5–10 m, off coast of Penghu is.,Taiwan, Jun. 2008). Pharm: Anti-inflammatory (10 μmol/L, elastase release inhibitor, fMLP/CB-induced hmn neutrophils, InRt = (45.51 ± 2.69)%, p < 0.001, IC50 > 10 μmol/L, control LY294002, IC50 = (4.12 ± 0.92)μmol/L). Ref: Y. N. Lee, et al, Mar. Drugs, 2013, 11, 2741 HO

OH

O O

H O

H

OH H

H O O

298

3 Diterpenoids

895 Krempfielin L Type: Eunicellane diterpenoids. C22H36O6 Colorless oil, [α]D25 = +26° (c = 0.8, CHCl3). Source: Soft Coral Cladiella krempfi (depth of 5–10 m, off coast of Penghu is.,Taiwan, Jun. 2008) and Cladiella sp. (Taiwan water). Pharm: Anti-inflammatory (10 μmol/L, elastase release inhibitor, fMLP/CB-induced hmn neutrophils, InRt = (18.67 ± 5.75)%, p < 0.05, IC50 > 10 μmol/L, control LY294002, IC50 = (4.12 ± 0.92) μmol/L). Ref: Y. N. Lee, et al, Mar. Drugs, 2013, 11, 2741│T. -H. Chen, et al, Mar. Drugs, 2014, 12, 2144 H

HO

H

OH OH O

H

H

O O

896 Krempfielin M Type: Eunicellane diterpenoids. C24H38O7 Colorless oil, [α]D25 = +24° (c = 2.4, CHCl3). Source: Soft Coral Cladiella krempfi (depth of 5–10 m, off coast of Penghu is.,Taiwan, Jun. 2008). Pharm: Anti-inflammatory (10 μmol/L, elastase release inhibitor, fMLP/CB-induced hmn neutrophils, InRt = (27.30 ± 5.42)%, p < 0.01, IC50 > 10 μmol/L, control LY294002, IC50 = (4.12 ± 0.92)μmol/L). Ref: Y. N. Lee, et al, Mar. Drugs, 2013, 11, 2741

O

H

H

OH OH O

O H

H

O O

897 Krempfielin N Type: Eunicellane diterpenoids. C25H42O6 Colorless oil, [α]D25 = +27.3° (c = 0.91, CHCl3). Source: Soft coral Cladiella krempfi (collected by hand, depth of 5–10 m, off coast of Penghu is., Taiwan, in June 2008, stored in freezer until extraction, voucher sample 200806CK). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μmol/L, InRt = low), control LY294002 (phosphatidylinositol-3-kinase inhibitor), IC50 = (1.88 ± 0.45)μmol/L); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μmol/L, InRt = (73.86 ± 14.18)%, IC50 = (4.94 ± 1.68)μmol/L), control LY294002, IC50 = (4.12 ± 0.92)μmol/L, may warrant further biomedical investigation). Ref: Y. -N. Lee, et al, Mar. Drugs, 2014, 12, 1148

3.15 Eunicellane diterpenoids

H H

HO

299

OH O O

H H

O O

898 Krempfielin O Type: Eunicellane diterpenoids. C28H44O9 Colorless oil, [α]D25 = −56.7° (c = 0.3, CHCl3). Source: Soft coral Cladiella krempfi (depth of 5–10 m, off coast of Penghu is., Taiwan). Pharm: Anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μmol/L, InRt = (13.33 ± 3.56)%, IC50 > 10 μmol/L), control LY294002, IC50 = (4.12 ± 0.92)μmol/L). Ref: Y. -N. Lee, et al, Mar. Drugs, 2014, 12, 1148 O O O

H

O

H

OH OH

O H

H

O O

899 Krempfielin P Type: Eunicellane diterpenoids. C26H40O7 Colorless oil, [α]D25 = +13.1° (c = 3.8, CHCl3). Source: Soft coral Cladiella krempfi (depth of 5–10 m, off coast of Penghu is., Taiwan). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μmol/L, InRt = 23%), control LY294002, IC50 = (1.88 ± 0.45)μmol/L, may warrant further biomedical investigation); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μmol/L, InRt = (35.54 ± 3.17)%, IC50 > 10 μmol/L), control LY294002, IC50 = (4.12 ± 0.92)μmol/L). Ref: Y. -N. Lee, et al, Mar. Drugs, 2014, 12, 1148 O O

H

H

OH OH O

H

H

O O

300

3 Diterpenoids

900 Labiatin B Type: Eunicellane diterpenoids. C26H38O8 Oil, [α]D = +22.5° (c = 0.3, CHCl3). Source: Gorgonian Eunicella labiata. Pharm: Cytotoxic (hmn colorectal cancer cells). Ref: V. Roussis, et al, Tetrahedron, 1996, 52, 2735 O O

H

O

O O

O H

O O

901 Litophynin A Type: Eunicellane diterpenoids. C24H38O3 Oil, [α]D20 = −16.5° (c = 0.23, EtOH). Source: Soft coral Litophyton sp. Pharm: Insecticide (silkworm Bombyx mori). Ref: M. Ochi, et al, Chem. Lett., 1987, 2207│M. Ochi, et al, Tennen Yuki Kagobutsu, 1988, 30, 204│K. A. El Sayed, et al, J. Agric. Food Chem., 1997, 45, 2735 H O H O O

902 Litophynin B Type: Eunicellane diterpenoids. C28H44O5 Needles, mp 99.5–100.5 °C, [α]D20 = −78.8° (c = 0.19, EtOH). Source: Soft coral Litophyton sp. Pharm: Insecticide. Ref: M. Ochi, et al, Chem. Lett., 1987, 2207│P. Bernardelli, et al, Heterocycles, 1998, 49, 531 O O H O H O O

903 Litophynin C Type: Eunicellane diterpenoids. C24H38O4 Oil, [α]D24 = −2.3° (c = 0.9, CHCl3). Source: Soft coral Litophyton sp. Pharm: Insecticide. Ref: M. Ochi, et al, Chem. Lett., 1987, 2207; 1988, 1661│P. Bernardelli, et al, Heterocycles, 1998, 49, 531

3.15 Eunicellane diterpenoids

301

H

HO

O H O O

904 Litophynin D Type: Eunicellane diterpenoids. C28H42O7 Oil, [α]D22.5 = −32.5° (c = 0.14, CHCl3). Source: Soft coral Litophyton sp. Pharm: Toxic (brine shrimp). Ref: M. Ochi, et al, Chem. Lett., 1987, 2207; 1990, 2183 O

H

O

O O

O

H

O O

905 Litophynin E (1R*,2R*,3R*,6S*,7S*,9R*,10R*,14R*)-3-Butanoyloxycladiell-11(17)-en-6,7-diol Type: Eunicellane diterpenoids. C24H40O5 Oil, [α]D20 = −13.1° (c = 0.21, CHCl3). Source: Soft corals Cladiella krempfi (Penghu Is., Taiwan) and Litophyton sp., soft coral Cladiella hirsuta (depth of 10 m, off coast of Sianglu Islet (23°32’ N, 119°38’ E), Penghu Islands, Taiwan, in June 2008) (Huang, 2014). Pharm: Anti-inflammatory (immunoblot analysis assay, RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 15%, P < 0.05); ichthyotoxic; anti-inflammatory (inhibitor of superoxide anion generation, 10 μmol/L, InRt = (1.0 ± 1.9)%, IC50 > 10 μmol/ L); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μmol/L, InRt = (6.1 ± 5.6)%, IC50 > 10 μmol/L) (Huang, 2014). Ref: M. Ochi, et al, Chem. Lett., 1990, 2183│C. B. Rao,et al, JNP, 1994, 57, 574│C. -J. Tai, et al, Mar. Drugs, 2011, 9, 2036│T. -Z. Huang, et al, Mar. Drugs, 2014, 12, 2446 OH OH

H O H

O O

906 Litophynin F Type: Eunicellane diterpenoids. C24H38O4 Amorph. solid, [α]D24 = −9.4° (c = 0.43, CHCl3). Source: Soft corals Litophyton sp. and Cladiella krempfi (depth of 5–10 m, off

302

3 Diterpenoids

coast of Penghu is.,Taiwan, Jun. 2008). Pharm: Cytotoxic (A549, ED50 = (12.2 ± 1.1)μg/ mL, control Taxol, ED50 = (1.5 ± 0.9)μg/mL; BT-483, ED50 = (6.8 ± 0.6)μg/mL, Taxol, ED50 = (3.9 ± 0.8)μg/mL; H1299, ED50 = (12.8 ± 1.2)μg/mL, Taxol, ED50 = (1.2 ± 0.1)μg/ mL; HepG2, ED50 = (11.1 ± 0.4)μg/mL, Taxol, ED50 = (1.4 ± 0.7)μg/mL; SAS, ED50 = (10.3 ± 0.5)μg/mL, Taxol, ED50 = (2.3 ± 1.5)μg/mL; BEAS2B, ED50 = (13.6 ± 0.5)μg/mL, Taxol, ED50 = (2.3 ± 1.5)μg/mL); anti-Inflammatory (reduces COX-2 protein expression in LPS-stimulated RAW264.7 macrophage cells, significant). Ref: M. Ochi, et al, Heterocycles, 1991, 32, 29│C. J. Tai, et al, Mar. Drugs, 2013, 11, 788 H

OH 6

9

O 13

H O O

907 Litophynin H Type: Eunicellane diterpenoids. C24H38O5 Amorph. solid, [α]D20 = +31.4° (c = 0.12, CHCl3). Source: Soft coral Litophyton sp. Pharm: Ichthyotoxin; hemolytic. Ref: M. Ochi, et al, Heterocycles, 1991, 32, 29│T. Miyamoto, et al, JNP, 1994, 57, 1212

HO

OH

H O H

O O

908 Litophynin I Type: Eunicellane diterpenoids. C24H40O6 Needles, mp 122.5–123.5 °C, [α]D20 = +45.2° (c = 0.58, CHCl3). Source: Soft coral Litophyton sp. Pharm: Repels and are toxic (prosobranch Drupella fragum). Ref: M. Ochi, et al, Chem. Lett., 1992, 155

HO

OH

H

OH

8

O H

O O

909 Litophynin I 3-acetate Type: Eunicellane diterpenoids. C26H42O7 Colorless oil, [α]D = +40.1° (c = 0.3, CHCl3). Source: Soft coral Litophyton sp. and Cladiella krempfi (depth of 5–10 m, off

3.15 Eunicellane diterpenoids

303

coast of Penghu is.,Taiwan, Jun. 2008). Pharm: Haemolytic. Ref: T. Miyamoto, et al, JNP, 1994, 57, 1212│C. J. Tai, et al, Mar. Drugs, 2013, 11, 788 OH

H

O

OH 9

O

O

12

H O O

910 Litophynin J Type: Eunicellane diterpenoids. C24H38O5 Needles, mp 120–121.5 °C, [α]D20 = +5.9° (c = 0.51, CHCl3). Source: Soft coral Litophyton sp. Pharm: Repels and are toxic (prosobranch Drupella fragum). Ref: M. Ochi, et al, Chem. Lett., 1992, 155

HO

H O O H

O O

911 Litophynol A Type: Eunicellane diterpenoids. C24H38O5 Amorphous solid, mp 131–132 °C, [α]D28 = +19.2° (c = 1.1, CHCl3). Source: Soft coral Litophyton sp. (mucus secreted, Japan). Pharm: Hemolytic; ichthyotoxic Ref: T. Miyamoto, et al, JNP, 1994, 57, 1212 OH OH O

O O

912 Litophynol B Type: Eunicellane diterpenoids. C24H40O6 Oil, [α]D28 = −17.6° (c = 3.1, CHCl3). Source: Soft Corals Cladiella krempfi (depth of 5–10 m, off coast of Penghu Is., Taiwan, Jun. 2008) and Litophyton sp. Pharm: Anti-inflammatory (immunoblot analysis assay, RAW264.7, 10 μmol/L, inhibition of LPS induced upregulation of iNOS, inhibited iNOS to ≈ 35%, P < 0.05); ichthyotoxic; anti-inflammatory (10 μmol/ L, elastase release inhibitor, fMLP/CB-induced hmn neutrophils, InRt = (6.15 ± 3.42)%, IC50 > 10 μmol/L, control LY294002, IC50 = (4.12 ± 0.92)μmol/L); haemolytic;

304

3 Diterpenoids

Ref: T. Miyamoto,et al, JNP, 1994, 57, 1212│C. -J. Tai, et al, Mar. Drugs, 2011, 9, 2036│Y. N. Lee, et al, Mar. Drugs, 2013, 11, 2741 H

HO

OH OH

O H

O O

913 6-Methyl ether of litophynol B Type: Eunicellane diterpenoids. C25H42O5 Source: Soft Coral Cladiella krempfi (depth of 5–10 m, off coast of Penghu is.,Taiwan, Jun. 2008). Pharm: Cytotoxic (A549, ED50 = (16.1 ± 1.2)μg/mL, control Taxol, ED50 = (1.5 ± 0.9)μg/mL; BT-483, ED50 = (10.0 ± 1.8) μg/mL, Taxol, ED50 = (3.9 ± 0.8)μg/mL; H1299, ED50 = (11.8 ± 1.0)μg/mL, Taxol, ED50 = (1.2 ± 0.1)μg/mL; HepG2, ED50 > 20 μg/mL, Taxol, ED50 = (1.4 ± 0.7)μg/mL; SAS, ED50 = (17.2 ± 0.4)μg/mL, Taxol, ED50 = (2.3 ± 1.5)μg/mL; BEAS2B, ED50 = (10.4 ± 0.3)μg/mL, Taxol, ED50 = (2.3 ± 1.5)μg/mL); anti-Inflammatory (inhibits accumulation of pro-inflammatory iNOS protein, potent); anti-Inflammatory (reduces expression of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells, significant). Ref: T. Iwagawa, et al, Heterocycles 2011, 83, 2149│C. J. Tai, et al, Mar. Drugs, 2013, 11, 788 H

H

OH O O

H

H

O O

914 Muricellin Type: Eunicellane diterpenoids. C26H38O8 Oil, [α]D25 = −132° (c = 0.5, CHCl3). Source: Gorgonians Muricella sp. (Korea waters) and Astrogorgia sp. (Beibuwan Bay, Guangxi, China). Pharm: Cytotoxic (K562, LC50 = 1.4 μg/mL); PLA2 inhibitor (50 μg/mL, InRt = 49%); antifoulant (barnacle Balanus Amphitrite, EC50 = 8.73 μg/mL). Ref: Y. Seo, et al, NPL, 2000, 14, 197│D. Lai, et al, JNP, 2012, 75, 1595 H O

O O

H O

O HO O

O

3.15 Eunicellane diterpenoids

305

915 Ophirin Type: Eunicellane diterpenoids. C26H38O7 Cryst., mp 133–134 °C, mp 94–95 °C, [α]D25 = −119.7° (c = 1, CHCl3); Colorless gum, [α]D25 = −35.3° (c = 0.1, CHCl3). Source: Gorgonians Muricella spp., Calicogorgia sp. and Astrogorgia sp. (Beibuwan Bay, Guangxi, China). Pharm: Inhibits cell division (fertilised starfish eggs); toxic (brine shrimp); inhibits cAMP phosphodiesterase and anti-inflammatory; cytotoxic; antifoulant (barnacle Balanus Amphitrite, EC50 > 25 μg/mL). Ref: Y. Kashman, Tet. Lett., 1980, 21, 879│N. Fusetani, et al, Tet. Lett., 1989, 30, 7079│M. Ochi, et al, Heterocycles, 1991, 32, 19│Y. Seo, et al, JNP, 1997, 60, 171│D. Lai, et al, JNP, 2012, 75, 1595 H O O

H

O

O O

O

O

916 Pachycladin A Type: Eunicellane diterpenoids. C26H44O7 Colorless oil, [α]D25 = −16.0° (c = 0.48, CHCl3). Source: Soft coral Cladiella pachyclados (Red Sea). Pharm: Anti-migration (wound-healing assay, PC3, 50 μmol/L, migration ≈ 28%, potent, control 4Hydroxyphenylmethylene hydantoin, 200 μmol/L, migration ≈ 25%); anti-invasive activity (Cultrex cell invasion assay, PC3, 50 μmol/L, invasion ≈ 2%, most active, control 4-Mercaptoethylphenylmethylene hydantoin (S-Et-PMH), 50 μmol/L, invasion ≈ 50%). Ref: H. M. Hassan, et al, JNP, 2010, 73, 848 O O

OH OH

H O H

O O

917 Pachycladin B Type: Eunicellane diterpenoids. C26H42O7 Colorless oil, [α]D25 = −12.7° (c = 0.23, CHCl3). Source: Soft coral Cladiella pachyclados (Red Sea). Pharm: Anti-migration (wound-healing assay, PC3, 50 μmol/L, migration ≈ 60%, moderate, control 4Hydroxyphenylmethylene hydantoin, 200 μmol/L, migration ≈ 25%). Ref: H. M. Hassan, et al, JNP, 2010, 73, 848

306

3 Diterpenoids

O O

H

OH O

HO

H

O O

918 Pachycladin C Type: Eunicellane diterpenoids. C22H34O4 Colorless oil, [α]D25 = −20.1° (c = 0.31, CHCl3). Source: Soft coral Cladiella pachyclados (Red Sea). Pharm: Anti-migration (wound-healing assay, PC3, 50 μmol/L, migration ≈ 55%, moderate, control 4Hydroxyphenylmethylene hydantoin, 200 μmol/L, migration ≈ 25%). Ref: H. M. Hassan, et al, JNP, 2010, 73, 848 H

O O

H

O OH

919 Pachycladin D Type: Eunicellane diterpenoids. C20H30O3 Yellowish-white gummy residue, [α]D25 = −24.2° (c = 0.12, CHCl3). Source: Soft coral Cladiella pachyclados (Red Sea). Pharm: Anti-migration (wound-healing assay, PC3, 50 μmol/L, migration ≈ 30%, potent, control 4-Hydroxyphenylmethylene hydantoin, 200 μmol/L, migration ≈ 25%). Ref: H. M. Hassan, et al, JNP, 2010, 73, 848 H O O

OH

H

920 (−)-Polyanthelin A Type: Eunicellane diterpenoids. C22H36O4 Oil, [α]D20 = −9.9° (c = 1, CHCl3). Source: Gorgonian Briareum polyanthes (Puerto Rico). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 = 16 μg/mL); antituberculosis (Mycobacterium tuberculosis H37Rv, 6.25 μg/mL no significant inhibitory activity). Ref: C. A. Ospina, et al, JNP, 2003, 66, 357

3.15 Eunicellane diterpenoids

307

O O

H O

O

H

921 (+)-Polyanthelin A Type: Eunicellane diterpenoids. C22H36O4 [α]D25 = +8.0° (c = 0.73, CHCl3). Source: Soft coral Cladiella pachyclados (Red Sea). Pharm: Anti-migration (wound-healing assay, PC3, 50 μmol/L, migration ≈ 25%, potent, control 4-Hydroxyphenylmethylene hydantoin, 200 μmol/L, migration ≈ 25%); anti-invasive activity (Cultrex cell invasion assay, PC3, 50 μmol/L, invasion ≈ 18%, active, control 4-Mercaptoethylphenylmethyl-ene hydantoin (S-Et-PMH), 50 μmol/L, invasion ≈ 50%). Ref: B. F. Bowden, et al, Aust. J. Chem., 1989, 42, 1705│H. M. Hassan, et al, JNP, 2010, 73, 848 O O

H O

O

H

922 Polyanthellin A Type: Eunicellane diterpenoids. C22H36O4 Oil, [α]D20 = −9.9° (c = 1.0, CHCl3). Source: Gorgonian Briareum polyanthes (Puerto Rico). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 = 16 μg/mL). Ref: C. A. Ospina, et al, JNP, 2003, 66, 357 O O

H 11S*

10R*

14S* 1S*

H

7R* 9S*

O

2S*

O 3S*

15

923 Sarcodictyin A Type: Eunicellane diterpenoids. C28H36N2O6 Powder (MeOH), mp 219–222 °C Source: Stolonifer Sarcodictyon roseum, soft coral Eleutherobia aurea. Pharm: Histidine decarboxylase inhibitor; cytotoxic (shows potent antitumour activity, induces tubulin polymerization). Ref: M. D’Ambrosio, et al, Helv. Chim. Acta, 1987, 70, 2019; 1988, 71, 964│S. Ketzinel, et al, JNP, 1996, 59, 873│K. C. Nicolaou, et al, Angew. Chem., Int. Ed., 1998, 37, 1418

308

3 Diterpenoids

O N

O H

N O

H

OH O

O

924 Sarcodictyin B Type: Eunicellane diterpenoids. C29H38N2O6 Oil, [α]D20 = −4.36° (c = 0.27, EtOH). Source: Stolonifer Sarcodictyon roseum. Pharm: Histidine decarboxylase inhibitor; cytotoxic (shows potent antitumour activity, induces tubulin polymerization). Ref: M. D’Ambrosio, et al, Helv. Chim. Acta, 1987, 70, 2019; 1988, 71, 964│S. Ketzinel, et al, JNP, 1996, 59, 873│K. C. Nicolaou, et al, Angew. Chem., Int. Ed., 1998, 37, 1418 O N

O H

N O

H

OH O

O

925 Sclerophytin A Type: Eunicellane diterpenoids. C20H34O4 Needles (C6H6), mp 187 °C. Source: Soft corals Cladiella pachyclados (Red Sea), Sclerophytum capitalis (Enewetak, Marshall Is., Pacific Ocean), Cladiella krempfi (depth of 5–10 m, off coast of Penghu is.,Taiwan, Jun. 2008) and Klyxum molle (depth of 10 m, along coast of Penghu Islands, Taiwan, in Jun. 2008) (Chang, 2014). Pharm: Anti-migration (wound-healing assay, PC3, 50 μmol/L, migration ≈ 17%, potent, control 4Hydroxyphenylmethylene hydantoin, 200 μmol/L, migration ≈ 25%); anti-invasive activity (Cultrex cell invasion assay, PC3, 50 μmol/L, invasion ≈ 37%, active, control 4-Mercaptoethylphenylmethylene hydantoin (S-Et-PMH), 50 μmol/L, invasion ≈ 50%). Ref: P. Sharma, et al, JCS Perkin I, 1988, 2537│D. Friedrich, et al, Org. Lett., 2000, 2, 1879 (revised constitution)│F. Gallou, et al, Org. Lett., 2001, 3, 135│P. Bernardelli, et al, JACS, 2001, 123, 9021│D. W. C. MacMillan, et al, JACS, 2001, 123, 9033│H. M. Hassan, et al, JNP, 2010, 73, 848│C. J. Tai, et al, Mar. Drugs, 2013, 11, 788│F. -Y. Chang, et al, Mar. Drugs, 2014, 12, 3060

3.15 Eunicellane diterpenoids

309

OH OH

H O H

OH

926 Sclerophytin A methyl ether Type: Eunicellane diterpenoids. C21H36O4 Cryst. (MeOH), mp 202–203 °C. Source: Soft corals Cladiella pachyclados (Red Sea) and Cladiella krempfi. Pharm: Antimigration (wound-healing assay, PC3, 50 μmol/L, migration ≈ 23%, potent, control 4-Hydroxyphenylmethylene hydantoin, 200 μmol/L, migration ≈ 25%); anti-invasive activity (Cultrex cell invasion assay, PC3, 50 μmol/L, invasion ≈ 10%, active, control 4-Mercaptoethylphenylmethylene hydantoin (S-Et-PMH), 50 μmol/L, invasion ≈ 50%). Ref: N. S. Sarma, et al, JNP, 1993, 56, 1977│J. Su, et al, JNP, 1993, 56, 1601│H. M. Hassan, et al, JNP, 2010, 73, 848 OH O

H O H

OH

927 Sclerophytin B Type: Eunicellane diterpenoids. C22H36O5 Needles (Me2CO), mp 190–192 °C. Source: Soft corals Cladiella australis (Andaman and Nicobar Is., Indian Ocean), Sclerophytum capitalis (Enewetak, Marshall Is., Pacific Ocean), Cladiella krempfi (depth of 5–10 m, off coast of Penghu is.,Taiwan, Jun. 2008) and Klyxum molle (depth of 10 m, along coast of Penghu Islands, Taiwan, in June 2008) (Chang, 2014). Pharm: Anti-migration (wound-healing assay, PC3, 50 μmol/L, migration ≈ 54%, moderate, control 4-Hydroxyphenylmethylene hydantoin, 200 μmol/L, migration ≈ 25%); cytotoxic (MTT colorimetric method, CCRF-CEM, ED50 = 4.2 μg/mL, K562, ED50 = 15.0 μg/mL, Molt4, ED50 = 16.5 μg/mL, T47D, ED50 = 12.4 μg/mL, cell proliferation inhibitor, strong) (Chang, 2014). Ref: P. Sharma, et al, JCS Perkin I, 1988, 2537│C. B. Rao, et al, JNP, 1994, 57, 574│D. S. Rao, et al, Indian J. Chem., Sect. B, 1994, 33, 198│D. Friedrich, et al, Org. Lett., 2000, 2, 1879 (revised constitution)│H. M. Hassan, et al, JNP, 2010, 73, 848│C. J. Tai, et al, Mar. Drugs, 2013, 11, 788│F. -Y. Chang, et al, Mar. Drugs, 2014, 12, 3060 OH O

H O

O H OH

310

3 Diterpenoids

928 Sclerophytin F Type: Eunicellane diterpenoids. C22H34O4 Gum, [α]D = +55° (c = 0.2, CHCl3). Source: Soft corals Sclerophytum capitalis and Cladiella krempfi (depth of 5–10 m, off coast of Penghu is.,Taiwan, Jun. 2008). Pharm: Anti-inflammatory (10 μmol/L, elastase release inhibitor, fMLP/CB-induced hmn neutrophils, InRt = (−0.32 ± 0.81)%, IC50 > 10 μmol/L, control LY294002, IC50 = (4.12 ± 0.92)μmol/L). Ref: M. Alam, et al, JOC, 1989, 54, 1896│Y. N. Lee, et al, Mar. Drugs, 2013, 11, 2741 OH H OH O H OH

929 Simplexin A Type: Eunicellane diterpenoids. C26H42O6 Oil, [α]D26 = −8.9° (c = 0.8, CHCl3). Source: Soft corals Klyxum simplex (Dongsha Atoll, South China Sea) and Klyxum simplex. Pharm: Cytotoxic (K562, ED50 > 20 μg/mL, control 5-FU, ED50 = (2.3 ± 0.2) μg/mL; CCRF-CEM, ED50 = (17.0 ± 2.9)μg/mL, 5-FU, ED50 = (1.8 ± 0.3)μg/mL; T47D, ED50 > 20 μg/mL, 5-FU, ED50 = (9.8 ± 1.5)μg/mL; Molt4, ED50 = (18.2 ± 2.6)μg/mL, 5FU, ED50 = (2.3 ± 0.3)μg/mL) (Wu, 2012); . Cytotoxic (Doay, ED50 = 10.37 μg/mL; MCF7, ED50 = 12.06 μg/mL; HeLa, ED50 > 20 μg/mL; Hep2, ED50 = 12.10 μg/mL; control Mitomycin: Doay, ED50 = 0.09 μg/mL; MCF7, ED50 = 0.14 μg/mL; HeLa, ED50 = 0.08 μg/mL; Hep2, ED50 = 0.02 μg/mL) (Wu, 2009). Ref: S. -L. Wu, et al, JNP, 2009, 72, 994│S. -L. Wu, et al, Mar. Drugs, 2012, 10, 1203

O

O

H 4

9

O

OH

12

H O O

930 Simplexin D Type: Eunicellane diterpenoids. C34H56O11 Oil,[α]D26 = +9° (c = 1, CHCl3). Source: Soft coral Klyxum simplex (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (Doay, ED50 = 15.34 μg/mL; MCF7, ED50 = 12.06 μg/mL; HeLa, ED50 > 20 μg/mL; Hep2, ED50 > 20 μg/mL; control Mitomycin: Doay, ED50 = 0.09 μg/mL; MCF7, ED50 = 0.14 μg/mL); only had an effect on iNOS protein expression. Ref: S. L. Wu, et al, JNP, 2009, 72, 994

3.15 Eunicellane diterpenoids

311

O HO O

H

O 4

9

O

2

OH O

12

O

H

O

O O

931 Simplexin E Type: Eunicellane diterpenoids. C33H52O11 Oil,[α]D26 = +14° (c = 2.3, CHCl3). Source: Soft coral Klyxum simplex (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (Doay, ED50 = 12.76 μg/mL; MCF7, ED50 = 7.19 μg/mL; HeLa, ED50 = 17.36 μg/mL; Hep2, ED50 = 10.72 μg/mL; control Mitomycin: Doay, ED50 = 0.09 μg/mL; MCF7, ED50 = 0.14 μg/mL; HeLa, ED50 = 0.08 μg/mL; Hep2, ED50 = 0.02 μg/mL); anti-inflammatory (LPS-stimulated RAW264.7 cells, inhibits up-regulation of proinflammatory iNOS and COX-2 proteins, 10 μmol/L, reduce levels of iNOS and COX-2 proteins to (4.8 ± 1.8)% and (37.7 ± 4.7)%, respectively, IC50 < 10 μmol/L). Ref: S. L. Wu, et al, JNP, 2009, 72, 994 O HO O

H

O 4

9

O

2

OH O

12

O

H

O

O O

932 Simplexin M Type: Eunicellane diterpenoids. C30H48O9 Source: Soft coral Klyxum simplex (Dongsha Atoll, South China Sea). Pharm: iNOS accumulation inhibitor (stimulated macrophages). Ref: S. -L. Wu, et al, Bull. Chem. Soc. Jpn., 2011, 84, 626 HO O O

H OH O

O

H O

O O

933 Simplexin N Type: Eunicellane diterpenoids. C30H48O10 Source: Soft coral Klyxum simplex (Dongsha Atoll, South China Sea). Pharm: iNOS accumulation inhibitor (stimulated macrophages). Ref: S. -L. Wu, et al, Bull. Chem. Soc. Jpn., 2011, 84, 626

312

3 Diterpenoids

HO O O

H O O

O

OH

O

H

O

O

934 Simplexin O Type: Eunicellane diterpenoids. C28H44O10 Source: Soft coral Klyxum simplex (Dongsha Atoll, South China Sea). Pharm: iNOS accumulation inhibitor (stimulated macrophages). Ref: S. -L. Wu, et al, Bull. Chem. Soc. Jpn., 2011, 84, 626 HO O O

H O O

O

OH

O

H

O

O

935 Simplexin P Type: Eunicellane diterpenoids. C26H42O7 White powder, mp 179.0–180.0 °C, [α]D26 = −27° (c = 1.2, CHCl3). Source: Soft coral Klyxum simplex (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (K562, ED50 > 20 μg/mL, control 5-FU, ED50 = (2.3 ± 0.2)μg/mL; CCRF-CEM, ED50 = (12.0 ± 1.6)μg/mL, 5-FU, ED50 = (1.8 ± 0.3)μg/mL; T47D, ED50 > 20 μg/mL, 5-FU, ED50 = (9.8 ± 1.5)μg/mL; Molt4, ED50 = (30.3 ± 3.4)μg/ mL, 5-FU, ED50 = (2.3 ± 0.3)μg/mL). Ref: S. -L. Wu, et al, Mar. Drugs, 2012, 10, 1203 HO O

H

OH O

O H

O O

936 Simplexin Q Type: Eunicellane diterpenoids. C26H42O7 Colorless oil, [α]D26 = −11° (c = 0.8, CHCl3). Source: Soft coral Klyxum simplex (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (K562, CCRF-CEM, T47D and Molt4, all ED50s > 20 μg/mL). Ref: S. -L. Wu, et al, Mar. Drugs, 2012, 10, 1203

3.15 Eunicellane diterpenoids

313

O O

H OH O

HO

H

O O

937 Simplexin R Type: Eunicellane diterpenoids. C24H38O8 White powder, mp 167–168 °C, [α]D26 = −27° (c = 0.4, CHCl3). Source: Soft coral Klyxum simplex (Dongsha Atoll, South China Sea). Pharm: Cytotoxic (K562, ED50 = (7.2 ± 2.4)μg/mL, control 5FU, ED50 = (2.3 ± 0.2)μg/mL; CCRF-CEM, ED50 = (2.7 ± 0.1)μg/mL, 5-FU, ED50 = (1.8 ± 0.3)μg/mL; T47D, ED50 = (13.5 ± 2.8)μg/mL, 5-FU, ED50 = (9.8 ± 1.5)μg/ mL; Molt4, ED50 = (3.8 ± 0.5)μg/mL, 5-FU, ED50 = (2.3 ± 0.3)μg/mL). Ref: S. -L. Wu, et al, Mar. Drugs, 2012, 10, 1203 O O

H O OH

O HO

H

O O

938 Simplexin S Cladieunicellin G Type: Eunicellane diterpenoids. C22H36O5 Colorless oil, [α]D26 = −41° (c = 0.6, CHCl3). Source: Soft corals Klyxum simplex (Dongsha Atoll, South China Sea) and Cladiella sp. (Indonesia). Pharm: Cytotoxic (K562, ED50 > 20 μg/mL, control 5-FU, ED50 = (2.3 ± 0.2)μg/mL; CCRF-CEM, ED50 = (13.0 ± 0.9) μg/mL, 5-FU, ED50 = (1.8 ± 0.3)μg/mL; T47D, ED50 > 20 μg/mL, 5-FU, ED50 = (9.8 ± 1.5)μg/mL; Molt4, ED50 = (16.4 ± 3.1)μg/mL, 5-FU, ED50 = (2.3 ± 0.3)μg/ mL). Ref: S. -L. Wu, et al, Mar. Drugs, 2012, 10, 1203│Y. -H. Chen, et al, CPB, 2012, 60, 160 O O

H

OH O

H

OH

314

3 Diterpenoids

939 (−)-Solenopodin C Type: Eunicellane diterpenoids. C20H34O2 Colorless oil, [α]D22 = −51° (c = 0.17, CHCl3). Source: Soft coral Cladiella sp. (Indonesia). Pharm: Anti-inflammatory (superoxide anion O2•− generation inhibitor, 10 μg/mL, InRt = (45.82 ± 2.49)%); elastase release inhibitor (10 μg/mL, InRt = (40.45 ± 5.80)%). Ref: Y. -H. Chen, et al, Mar. Drugs, 2011, 9, 934 HO

O

H

H

H

940 Valdivone A Type: Eunicellane diterpenoids. C25H34O5 Needles, mp 89–91 °C, [α]D = +94.4° (c = 0.34, CHCl3). Source: Soft coral Alcyonium valdivae (South Africa). Pharm: Anti-inflammatory. Ref: Y. Lin, et al, Tetrahedron, 1993, 49, 7977 O O

H 7

O O

1

11

OH

H

941 Valdivone B Type: Eunicellane diterpenoids. C28H34O5 Needles, mp 171–173 °C, [α]D = +79.4° (c = 0.57, CHCl3). Source: Soft coral Alcyonium valdivae (South Africa). Pharm: Anti-inflammatory. Ref: Y. Lin, et al, Tetrahedron, 1993, 49, 7977 O H

O O

O

H

OH

3.16 Asbestinane diterpenoids

315

3.16 Asbestinane diterpenoids 942 11-Acetoxy-4-deoxyasbestinin B Type: Asbestinane diterpenoids. C22H34O4 Cryst., mp 150–152 °C, [α]D29 = −8.9° (c = 0.34, CHCl3). Source: Gorgonian Briareum asbestinum. Pharm: Cytotoxic; antibacterial (Klebsiella pneumonia). Ref: J. J. Morales, et al, JNP, 1991, 54, 1368│P. Bernardelli, et al, Heterocycles, 1998, 49, 531 O O

H O

H H O

943 11-Acetoxy-4-deoxyasbestinin D Type: Asbestinane diterpenoids. C22H34O4 Oil, [α]D29 = −2.29° (c = 1.3, CHCl3). Source: Gorgonian Briareum asbestinum. Pharm: Cytotoxic; antibacterial (Klebsiella pneumonia). Ref: J. J. Morales, et al, JNP, 1991, 54, 1368│P. Bernardelli, et al, Heterocycles, 1998, 49, 531 O O

H

H

O H O

944 Asbestinin 6 Type: Asbestinane diterpenoids. C30H48O6 Oil, [α]D25 = −75.9° (c = 4.08, CHCl3). Source: Gorgonian Briareum asbestinum (Puerto Rico). Pharm: Cytotoxic. Ref: A. D. Rodriguez, et al, Tetrahedron, 1993, 49, 319│A. D. Rodriguez, et al, JNP, 1994, 57, 1638 O O

H O H O

O O

316

3 Diterpenoids

945 Asbestinin 7 Type: Asbestinane diterpenoids. C30H48O7 Oil, [α]D25 = +5.0° (c = 3.2, CHCl3). Source: Gorgonian Briareum asbestinum (Puerto Rico). Pharm: Cytotoxic. Ref: A. D. Rodriguez, et al, Tetrahedron, 1993, 49, 319 O O

H

H

O

OH

H O

O O

946 Asbestinin 8 Type: Asbestinane diterpenoids. C28H44O5 Oil, [α]D25 = −49.0° (c = 3.9, CHCl3). Source: Gorgonian Briareum asbestinum (Puerto Rico). Pharm: Cytotoxic. Ref: A. D. Rodriguez, et al, Tetrahedron, 1993, 49, 319 O

H

11

7

O

H

6

O 4

H

O

O

947 Asbestinin 9 Type: Asbestinane diterpenoids. C24H36O5 Oil, [α]D27 = −78.0° (c = 2, CHCl3). Source: Gorgonian Briareum asbestinum (Puerto Rico). Pharm: Cytotoxic. Ref: A. D. Rodriguez, et al, Tetrahedron, 1993, 49, 319 O O 11

H O

H

6

O

H O

948 Asbestinin 10 Type: Asbestinane diterpenoids. C22H32O5 Oil, [α]D25 = −81.5° (c = 0.76, CHCl3). Source: Gorgonian Briareum asbestinum (Puerto Rico). Pharm: Cytotoxic. Ref: A. D. Rodriguez, et al, Tetrahedron, 1993, 49, 319

3.16 Asbestinane diterpenoids

317

O O 11

H O

H

O

6

H O

949 seco-Asbestinin Type: Asbestinane diterpenoids. C22H32O6 Colorless oil, [α]D25 = +21.14° (c = 3.5, CHCl3). Source: Gorgonians Briareum asbestinum (Mona I., Puerto Rico) (Bocas del Toro, Caribbean Sea, Panama). Pharm: Cytotoxic (HeLa and CHO-K1, weak). Ref: A. D. Rodriguez, et al, Tet. Lett., 1994, 35, 5793│J. F. Gómez-Reyes, et al, Mar. Drugs, 2012, 10, 2608 O

O O

H

H

O H O O

950 4-Deoxyasbestinin A Type: Asbestinane diterpenoids. C24H38O4 Oil, [α]D29 = −6.6° (c = 1.6, CHCl3). Source: Gorgonian Briareum asbestinum. Pharm: Cytotoxic; antibacterial (Klebsiella pneumonia). Ref: J. J. Morales, et al, JNP, 1991, 54, 1368│P. Bernardelli, et al, Heterocycles, 1998, 49, 531 O O

H O

H H O

951 4-Deoxyasbestinin C Type: Asbestinane diterpenoids. C24H38O4 Oil, [α]D29 = −1.2° (c = 0.84, CHCl3). Source: Gorgonian Briareum asbestinum. Pharm: Cytotoxic; antibacterial (Klebsiella

318

3 Diterpenoids

pneumonia). Ref: J. J. Morales, et al, JNP, 1991, 54, 1368│P. Bernardelli, et al, Heterocycles, 1998, 49, 531 O O

H O

H H O

3.17 Sphaerane diterpenoids 952 Bromosphaerol Type: Sphaerane diterpenoids. C20H32Br2O Viscous oil, [α]D = +0.5°. Source: Red alga Sphaerococcus coronopifolius. Pharm: Toxic (brine shrimp). Ref: E. Fattorusso, et al, Gazz. Chim. Ital., 1976, 106, 779│F. Cafieri, et al, Tet. Lett., 1979, 963; 1981, 22, 4123; 1984, 25, 3141│S. de Rosa, et al, Phytochemistry, 1988, 27, 1875 HO H Br

H

Br

953 Bromosphaerone Type: Sphaerane diterpenoids. C20H30Br2O3 Amorph. powder, [α]D = −71° (c = 0.1, CH2Cl2). Source: Red alga Sphaerococcus coronopifolius (Atlantic coast of Morocco). Pharm: Antibacterial (Staphylococcus aureus, MIC = 0.047 μg/mL). Ref: S. Etahiri, et al, JNP, 2001, 64, 1024 OH O

OH

H H Br

Br

3.18 Briarane diterpenoids

319

954 Sphaerococcenol A Type: Sphaerane diterpenoids. C20H29BrO2 Cryst. (CCl4), mp 184–185 °C, [α]D25 = −93° (c = 2, CHCl3). Source: Red alga Sphaerococcus coronopifolius. Pharm: Antibacterial (Staphylococcus aureus, high active); antiplasmodial (CRPF FcB1 strain, IC50 = 1 μmol/ L). Ref: W. Fenical, et al, Tet. Lett., 1976, 731│S. Etahiri, et al, JNP, 2001, 64, 1024 O

HO H H

Br

3.18 Briarane diterpenoids 955 Anthoptilide A Type: Briarane diterpenoids. C27H34O7 White needles, white solid, [α]D25 = +92.6° (c = 0.63, MeOH). Source: Sea pen Anthoptilum cf. kukenthali (Australia). Pharm: Inhibits [3H]CPDPX ([3H]1,3-dipropyl-8-cyclopentylxanthine) binding to ratbrain adenosine A1 receptor (IC50 = 420 μg/mL). Ref: N. B. Pham, et al, JNP, 2000, 63, 318 O

O O

O O

H

O O

956 Anthoptilide B Type: Briarane diterpenoids. C26H34O7 White needles, white solid, [α]D25 = +59.1° (c = 0.52, MeOH). Source: Sea pen Anthoptilum cf. kukenthali (Australia). Pharm: Inhibits [3H]CPDPX binding to ratbrain adenosine A1 receptor (IC50 = 45 μg/mL). Ref: N. B. Pham, et al, JNP, 2000, 63, 318

320

3 Diterpenoids

O

O O

O O

H

O O

957 Anthoptilide C Type: Briarane diterpenoids. C25H32O7 White powder, white needles, white solid, [α]D25 = +17.6° (c = 0.19, MeOH). Source: Sea pen Anthoptilum cf. kukenthali (Australia). Pharm: Inhibits [3H]CPDPX binding to ratbrain adenosine A1 receptor (IC50 = 3.1 μg/mL). Ref: N. B. Pham, et al, JNP, 2000, 63, 318 O

O O

O O

H

O O

958 Anthoptilide D Type: Briarane diterpenoids. C29H32O7 White powder, white needles, white solid, [α]D25 = +104.2° (c = 0.49, MeOH). Source: Sea pen Anthoptilum cf. kukenthali (Australia). Pharm: Inhibits [3H]CPDPX binding to ratbrain adenosine A1 receptor (IC50 = 500 μg/mL). Ref: N. B. Pham, et al, JNP, 2000, 63, 318 O

O O

O O

H

O O

3.18 Briarane diterpenoids

321

959 Anthoptilide E Type: Briarane diterpenoids. C27H36O8 Amorphous solid, [α]D25 = +2.2° (c = 0.28, MeOH). Source: Sea pen Anthoptilum cf. kukenthali (Australia). Pharm: Inhibits [3H] CPDPX binding to ratbrain adenosine A1 receptor (IC50 = 490 μg/mL). Ref: N. B. Pham, et al, JNP, 2000, 63, 318 O

O O

O O O H

O O

960 12-O-Benzoyl-12-O-deacetylpteroidine 12-Benzoyl-2,9,14-triacetoxy-6-chloro-4,8-epoxy-4,12-dihydroxy-5(16)-briaren-18,7olide Type: Briarane diterpenoids. C33H39ClO12 Cryst., mp 291–293 °C, [α]D = −4° (c = 0.54, CHCl3). Source: Octocorallia Pennatulacea (sea pen) Pteroeides laboutei. Pharm: Ichthyotoxic. Ref: A. Clastres, et al, JNP, 1984, 47, 155 O

O O

O

OH

O O Cl

O H O

O

O O

961 Benzyl briaviolide A Type: Briarane diterpenoids. C31H37ClO9 Colorless amorphous gum; [α]D24 = −21° (c = 0.2, CH2Cl2). Source: Gorgonian Briareum violacea (Benzoylation of Briaviolide A yielded monobenzoyl derivative). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μg/mL, InRt = (6.09 ± 4.09)%, p < 0.01, control Genistein, InRt = (65.05 ± 6.12)%, p < 0.01); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μg/mL, InRt = (28.60 ± 7.54)%), selective activity, p < 0.05, Genistein, InRt = (52.45 ± 6.34)%, p < 0.05). Ref: C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677

322

3 Diterpenoids

O O O 14

16

1 10

O H

5

Cl

OH O

O

O

O

962 Bis(deacyl)solenolide D Type: Briarane diterpenoids. C22H29ClO9 Glass, [α]D20 = −14.5° (c = 0.51, MeOH). Source: Sponge Psammaplysilla purpurea. Pharm: Biofilm formation and biofouling inhibitor. Ref: A. Yamada, et al, Bull. Chem. Soc. Jpn., 1997, 70, 3061 OH

O

O

OH

HO H

Cl O

O

O

O

963 Briacavatolide C Type: Briarane diterpenoids. C30H42O13 White amorphous powder, [α]D25 = +25.5° (c = 0.1, CHCl3). Source: Gorgonian Briareum excavatum (Orchid I., Taiwan). Pharm: AntiHCMV (confluent HEL cells, IC50 = 18 μmol/L, control Ganciclovir). Ref: T. -T. Yeh, et al, Mar. Drugs, 2012, 10, 1019 O

O O

O

OH

O O HO

H

O

O

O O O

964 Briacavatolide D Type: Briarane diterpenoids. C24H32O11 White amorphous powder, [α]D25 = −33.6° (c = 0.2, CHCl3). Source: Gorgonian Briareum excavatum (Orchid I., Taiwan). Pharm: AntiHCMV (confluent HEL cells, ED50 > 100 μmol/L, control Ganciclovir); cytotoxic (A549,

3.18 Briarane diterpenoids

323

HT29, P388 and HEL, ED50 > 100 μmol/L, control Mithramycin). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 2103 O

O O

O

OH OH

O

H

O O

OH

O

965 Briacavatolide E Type: Briarane diterpenoids. C28H40O12 White amorphous powder, [α]D25 = +22.3° (c = 0.1, CHCl3). Source: Gorgonian Briareum excavatum (Orchid I., Taiwan). Pharm: AntiHCMV (confluent HEL cells, ED50 > 100 μmol/L, control Ganciclovir); cytotoxic (A549, HT29, P388 and HEL, ED50 > 100 μmol/L, control Mithramycin). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 2103 O

O O

O

OH

O O HO

H

O O

OH

O

966 Briacavatolide F Type: Briarane diterpenoids. C30H42O13 White amorphous powder, [α]D25 = −27.6° (c = 0.1, CHCl3). Source: Gorgonian Briareum excavatum (Orchid I., Taiwan). Pharm: AntiHCMV (confluent HEL cells, ED50 = 22 μmol/L, control Ganciclovir); cytotoxic (A549, HT29, P388 and HEL, ED50 > 100 μmol/L, control Mithramycin). Ref: S. -K. Wang, et al, Mar. Drugs, 2012, 10, 2103 O

O O

O

OH

O O HO

H O

O

O O O

324

3 Diterpenoids

967 Briaexcavatin C Type: Briarane diterpenoids. C28H36O11 Powder, mp 79–81 °C, [α]D25 = −25° (c = 0.4, CHCl3). Source: Gorgonian Briareum excavatum (off coast of Southern Taiwan, depth of 10 m, October 2003, voucher in NMMBA). Pharm: Cytotoxic (MDA-MB-231, IC50 = 17.50 μg/mL, mild). Ref: P. -J. Sung, et al, Tetrahedron 2006, 62, 5686 O

O O

O

3 1

13

O

10

O

H O O

O

O

O

968 Briaexcavatin E Type: Briarane diterpenoids. C33H46O13 Powder, mp 251–252 °C, [α]D29 = +42° (c = 0.4, CHCl3). Source: Gorgonian Briareum excavatum (off coast of Southern Taiwan, depth of 10 m, October 2003, voucher in NMMBA). Pharm: Inhibits hmn neutrophil elastase (HNE) release (neutrophil, response to fMLP/CB: 3 μmol/L, InRt = 12%, 5 μmol/L, InRt = 34%, 10 μmol/L, InRt = 62% IC50 = 5 μmol/L–10 μmol/L). Ref: P. -J. Sung, et al, Tetrahedron 2006, 62, 5686 O

O

O O

O

O 3

O

13

1 10

O

H OO O

O O

969 Briaexcavatolide B Type: Briarane diterpenoids. C28H38O10 Powder, mp 219–221 °C, [α]D25 = −111° (c = 1.0, CHCl3). Source: Gorgonian Briareum excavatum. Pharm: Cytotoxic (P388, ED50 = 1.3 μg/mL, KB, ED50 = 1.5 μg/mL). Ref: J. -H, Sheu, et al, Tetrahedron, 1999, 55, 14555

3.18 Briarane diterpenoids

325

O O 3

O

1

13

O

10

H O O

HO

O

O

O

970 Briaexcavatolide F Type: Briarane diterpenoids. C26H35ClO10 Powder, mp 184–186 °C, [α]D25 = −21° (c = 0.1,MeOH). Source: Gorgonian Briareum excavatum. Pharm: Cytotoxic (A549, ED50 = 1.3 μg/mL). Ref: J. -H, Sheu, et al, Tetrahedron, 1999, 55, 14555 OH O

O

2

O 12 9

O

Cl

OH

H O

O O

O

971 Briaexcavatolide L Type: Briarane diterpenoids. C30H44O13 Powder, mp 164–166 °C, [α]D27 = −37° (c = 0.8, CHCl3). Source: Gorgonian Briareum excavatum (South Bay, Kenting, southernmost tip, Taiwan, depths of 4–5 m, July 1995). Pharm: Cytotoxic (P388, ED50 = 0.5 μg/mL). Ref: P. -J. Sung, et al, JNP, 2001, 64, 318 O

O

O

O

O

O 3

13

1 10

HO

OH

H O

O

O OH

O

972 Briaexcavatolide P Type: Briarane diterpenoids. C30H42O13 Cryst., mp 248–251 °C, [α]D27 = +167° (c = 1, MeOH). Source: Gorgonian Briareum excavatum. Pharm: Cytotoxic (P388, ED50 = 0.9 μg/mL). Ref: S. -L. Wu, et al, JNP, 2001, 64, 1415

326

3 Diterpenoids

O

O

O

O

O

OH

2

14

O

4

9

HO

H O O

O O

O

973 Brialalepolide A Type: Briarane diterpenoids. C26H34O11 Colorless crystalline solid (MeOH), mp 216–225 °C, [α]D21 = −110° (c = 0.001, acetone). Source: Gorgonian Briareum sp. (Vanuatu). Pharm: Cytotoxic (CaCo-2, 5–30 μmol/L). Ref: P. M. Joyner, et al, JNP, 2011, 74, 857 OH

O O

O O HO

H O O

OO O

974 Brialalepolide B Type: Briarane diterpenoids. C30H42O11 White powder, [α]D21 = −101° (c = 0.0024, CHCl3). Source: Gorgonian Briareum sp. (Vanuatu). Pharm: Cytotoxic (CaCo-2, 5–30 μmol/L); reducer of COX-2 expression (hmn colon adenocarcinoma cells and murine macrophage RAW264.7cells). Ref: P. M. Joyner, et al, JNP, 2011, 74, 857 OH

O O

O O HO

H O O

OO O

975 Brialalepolide C Type: Briarane diterpenoids. C32H46O11 White powder, [α]D21 = −102° (c = 0.0024, CHCl3). Source: Gorgonian Briareum sp. (Vanuatu). Pharm: Cytotoxic (CaCo-2, 5–30 μmol/L); reducer of COX-2 expression (hmn colon adenocarcinoma cells and murine macrophage RAW264.7cells). Ref: P. M. Joyner, et al, JNP, 2011, 74, 857

3.18 Briarane diterpenoids

327

O

OH

O

O O HO

H OO

O O

O

976 Brianolide Type: Briarane diterpenoids. C24H31ClO10 [α]D23 = −15° (c = 0.01, MeOH). Source: Gorgonians Briareum stechei (Western Pacific Ocean) and Briareum sp. Pharm: Anti-inflammatory. Ref: J. H. Sheu, et al, JNP, 1998, 61, 602│J. H. Kwak, et al, JNP, 2001, 64, 754 OH

O

O O OH

O

H

Cl O

O

O

O

977 Brianthein A Briviolide J Type: Briarane diterpenoids. C26H34O8 Amorph. powder, [α]D20 = +118.7° (c = 0.4, EtOH), [α]D = −104° (c = 0.07, MeOH), Source: Gorgonian Briareum excavatum. Pharm: Reverses MDR of hmn carcinoma cell line KB-C2 (3 μg/mL: KB-3–1 growth inhibition 11% (little cytotoxicity), 3 μg/mL + colchicine 0.1 μg/mL, KB-C2 growth inhibition 60%; 10 μg/mL: KB-3–1 growth inhibition 27% (little cytotoxicity), 10 μg/mL + colchicine 0.1 μg/mL, KB-C2 growth inhibition 84%, Brianthein A complitely reversed the resisitance to colchicine in KB-C2 cells). Ref: S. Aoki, et al, Tetrahedron, 2001, 57, 8951 O

O

O

O O

O

H

O O

328

3 Diterpenoids

978 Brianthein B Type: Briarane diterpenoids. C26H34O10 [α]D20 = +81.7° (c = 0.4, EtOH). Source: Gorgonian Briareum excavatum. Pharm: Reverses MDR of hmn carcinoma cell line KB-C2 (3 μg/mL: KB-3–1 growth inhibition 5% (little cytotoxicity), 3 μg/mL + colchicine 0.1 μg/mL, KB-C2 growth inhibition 26%; 10 μg/mL: KB-3–1 growth inhibition 26% (little cytotoxicity), 10 μg/mL + colchicine 0.1 μg/mL, KB-C2 growth inhibition 37%). Ref: S. Aoki, et al, Tetrahedron, 2001, 57, 8951

O O

O

H

O

O

O

O

O H

O O

979 Brianthein C Type: Briarane diterpenoids. C26H34O11 [α]D20 = +32.6° (c = 0.4, EtOH). Source: Gorgonian Briareum excavatum. Pharm: Reverses MDR of hmn carcinoma cell line KB-C2 (3 μg/mL: KB-3–1 growth inhibition 11% (little cytotoxicity), 3 μg/mL + colchicine 0.1 μg/mL, KB-C2 growth inhibition 0%; 10 μg/mL: KB-3–1 growth inhibition 17% (little cytotoxicity), 10 μg/mL + colchicine 0.1 μg/mL, KB-C2 growth inhibition 15%). Ref: S. Aoki, et al, Tetrahedron, 2001, 57, 8951 O O O

O

HO

H O O

O

O O O

980 Brianthein X Type: Briarane diterpenoids. C24H31ClO9 Cryst., mp 230–232 °C (dec). Source: Gorgonian Briareum polyanthes. Pharm: Insecticide. Ref: S. H. Grode, et al, JOC, 1983, 48, 5203

3.18 Briarane diterpenoids

329

OH O 2

O 12

9

O

OH

Cl

H

O

O

O

O

981 Brianthein Y Type: Briarane diterpenoids. C28H37ClO10 Cryst., mp 233–235 °C (dec). Source: Gorgonians Briareum polyanthes and Briareum asbestinum. Pharm: CNS depressant; toxic (grasshoppers). Ref: S. H. Grode, et al, JOC, 1983, 48, 5203 O O O 2

O 12

9

O

OH

Cl

H

O

O O

O

982 Briarenolide F Type: Briarane diterpenoids. C28H40O10 White powder, mp 141–142 °C, [α]D25 = +32° (c = 0.1, CHCl3). Source: Gorgonian Briareum sp. Pharm: Anti-inflammatory (superoxide anion O2•− generation inhibitor, fMLP/CB stimulated neutrophils, 10 μg/mL, InRt = (76.65 ± 4.21)%, IC50 = (3.82 ± 0.45)μg/mL, control DPI, IC50 = (0.82 ± 0.31)μg/mL); elastase release inhibitor (10 μg/mL, InRt = (27.48 ± 6.60)%, IC50 > 10 μg/mL, control Elastatinal, IC50 = (31.82 ± 5.92)μg/mL). Ref: P. -H. Hong, et al, Mar. Drugs, 2012, 10, 1156 O

O O

O O O

H HO

O O O

330

3 Diterpenoids

983 Briarenolide G Type: Briarane diterpenoids. C22H30O5 White powder, mp 78–80 °C, [α]D25 = −97° (c = 0.02, CHCl3). Source: Gorgonian Briareum sp. Pharm: Anti-inflammatory (superoxide anion O2•− generation inhibitor, fMLP/CB stimulated neutrophils, 10 μg/mL, InRt = (22.04 ± 3.43)%, IC50 > 10 μg/mL, control DPI, IC50 = (0.82 ± 0.31)μg/mL); elastase release inhibitor (10 μg/mL, InRt = (12.98 ± 4.68)%, IC50 > 10 μg/mL, control Elastatinal, IC50 = (31.82 ± 5.92)μg/mL). Ref: P. -H. Hong, et al, Mar. Drugs, 2012, 10, 1156 O O

OH

H

O O

984 Briareolate ester D Type: Briarane diterpenoids. C27H40O9 Cryst. (EtOAc/petrol), mp 160–163 °C, [α]D = −120° (c = 0.2, CHCl3). Source: Gorgonian Briareum asbestinum. Pharm: Toxic (brine shrimp). Ref: B. S. Mootoo, et al, Tetrahedron, 1996, 52, 9953│R. J. Meginley, et al, Mar. Drugs, 2012, 10, 1662 O

O O

O

2 14 12

HO

8

H O

7

O

O

O

985 Briareolate ester G Methyl 2-butanoyl-12-hydroxy-14-acetoxy-9-oxo-5,7-briaradien-18-oate Type: Briarane diterpenoids. C27H40O8 Cryst. (Me2CO/petrol), mp 99.5–101 °C, [α]D = −121.7° (c = 0.23, CHCl3). Source: Gorgonian Briareum asbestinum. Pharm: Toxic (brine shrimp). Ref: B. S. Mootoo, et al, Tetrahedron, 1996, 52, 9953│R. J. Meginley, et al, Mar. Drugs, 2012, 10, 1662

3.18 Briarane diterpenoids

331

O

O O

O

2 14 12

HO

7

8

H O

O O

986 Briareolate ester I Type: Briarane diterpenoids. C25H34O7 Gum, [α]D = −113.2° (c = 0.22, CHCl3). Source: Gorgonian Briareum asbestinum. Pharm: Toxic (brine shrimp). Ref: B. S. Mootoo, et al, Tetrahedron, 1996, 52, 9953 O O

O H

O

O

O

O

987 Briareolate ester K Type: Briarane diterpenoids. C33H50O10 Colorless oil, [α]D25 = −8° (c = 0.05, MeOH). Source: Gorgonian Briareum asbestinum (Boca Raton, Florida). Pharm: Cytotoxic (hmn embryonic stem cells BG02 growth inhibitor, EC50 = 40 μmol/L). Ref: R. J. Meginley, et al, Mar. Drugs, 2012, 10, 1662 O

O O

O O

2

14 12

8

O H O

7

O

O

O

332

3 Diterpenoids

988 Briareolate ester L Type: Briarane diterpenoids. C27H40O8 Source: Gorgonian Briareum asbestinum (Boca Raton, Florida). Pharm: Cytotoxic (hmn embryonic stem cells BG02 growth inhibitor, EC50 = 2.4 μmol/L, pancreatic cancer cells BXPC3 growth inhibitor, EC50 = 9.3 μmol/L). Ref: P. Gupta, et al, Org. Lett. 2011, 13, 3920│R. J. Meginley, et al, Mar. Drugs, 2012, 10, 1662 O

O O

O 2

14 12

7

HO

8

H O

O O

989 Briareolate ester M Type: Briarane diterpenoids. C33H50O9 Source: Gorgonian Briareum asbestinum (Boca Raton, Florida). Pharm: Cytotoxic (hmn embryonic stem cells BG02 growth inhibitor, EC50 = 8.0 μmol/L, pancreatic cancer cells BXPC3 growth inhibitor, EC50 = 17.0 μmol/L). Ref: P. Gupta, et al, Org. Lett. 2011, 13, 3920│R. J. Meginley, et al, Mar. Drugs, 2012, 10, 1662 O

O O

O 2

14 12

O O

7

H O

8

O O

990 Briareolate ester N Type: Briarane diterpenoids. C33H50O9 Source: Gorgonian Briareum asbestinum (Boca Raton, Florida). Pharm: Cytotoxic (hmn embryonic stem cells BG02 growth inhibitor, pancreatic cancer cells BXPC3 growth inhibitor). Ref: R. J. Meginley, et al, Mar. Drugs, 2012, 10, 1662

3.18 Briarane diterpenoids

333

O

O O

O

2 14

O

12

O

8

H

7

O

O O

991 Briareolide A Type: Briarane diterpenoids. C28H40O11 Needles (Me2CO/hexane), mp 242–243 °C. Source: Gorgonian Briareum sp. Pharm: Anti-inflammatory. Ref: E. O. Pordesimo, et al, JOC, 1991, 56, 2344 O

O O

O

HO

HO

H

O O

O O

O

992 Briareolide B Type: Briarane diterpenoids. C26H36O11 Needles (Me2CO/hexane), mp 249–250 °C. Source: Gorgonian Briareum sp. Pharm: Anti-inflammatory. Ref: E. O. Pordesimo, et al, JOC, 1991, 56, 2344 O

O O

O

HO

HO

H O O

O O O

334

3 Diterpenoids

993 Briareolide C Type: Briarane diterpenoids. C28H38O10 Powder (Me2CO/hexane), mp 139–140 °C. Source: Gorgonian Briareum sp. Pharm: Anti-inflammatory. Ref: E. O. Pordesimo, et al, JOC, 1991, 56, 2344 O

O O

O

O

H O O

O O

O

994 Briareolide D Type: Briarane diterpenoids. C26H34O10 Gum. Source: Gorgonian Briareum sp. Pharm: Anti-inflammatory. Ref: E. O. Pordesimo, et al, JOC, 1991, 56, 2344 O

O O

O

O

H O O

O O

O

995 Briareolide E Type: Briarane diterpenoids. C28H40O10 Foam, mp 182–183 °C (dec). Source: Gorgonian Briareum sp. Pharm: Anti-inflammatory. Ref: E. O. Pordesimo, et al, JOC, 1991, 56, 2344 O

O O

O

HO

H O O

O O O

3.18 Briarane diterpenoids

335

996 Briareolide K Type: Briarane diterpenoids. C26H36O8 Gum, [α]D = +116.1° (c = 0.16, CHCl3). Source: Gorgonian Briareum asbestinum. Pharm: Toxic (brine shrimp). Ref: B. S. Mootoo, et al, Tetrahedron, 1996, 52, 9953 O

O O

O

OH H

O

O

O

997 Briaviolide A (1S,2S,3Z,6S,7R,8R,9S,10S,11R,12R,13S,14R,17R)-6-Chloro-13,14-epoxy-2,9-diacetoxy-8,12dihydroxybriaran-3(4),5(16)-dien-18,7-olide Type: Briarane diterpenoids. C24H31ClO9 Colorless amorphous prism, mp 174–175 °C, [α] D24 = −79° (c = 0.5, CH2Cl2). Source: Gorgonian Briareum violacea (depth of 15 m, Pingtung county, Taiwan, in May 2007). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μg/mL, InRt = (6.09 ± 1.40)%, p < 0.05, control Genistein, InRt = (65.05 ± 6.12)%, p < 0.01); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μg/mL, InRt = (11.04 ± 7.22)%), Genistein, InRt = (52.45 ± 6.34)%, p < 0.05). Ref: C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677 O 15

O

O 14

16

1 10

20

H

Cl

OH

HO O

O 18

O

19

O

998 Briaviolide B Type: Briarane diterpenoids. C27H35ClO10 Colorless amorphous gum, [α]D24 = −45° (c = 0.1, CH2Cl2). Source: Gorgonian Briareum violacea (depth of 15 m, Pingtung county, Taiwan, in May 2007). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μg/mL, InRt = (6.43 ± 2.17)%, p < 0.05, control Genistein, InRt = (65.05 ± 6.12)%, p < 0.01); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μg/mL, InRt = (13.43 ± 2.66)%, p < 0.01), Genistein, InRt = (52.45 ± 6.34)%, p < 0.05). Ref: C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677

336

3 Diterpenoids

O O O O

14

1 10

O

Cl

OH

H

O

O O

O

999 Briaviolide C Type: Briarane diterpenoids. C28H36O12 Colorless powder, [α]D24 = −6° (c = 0.1, CH2Cl2). Source: Gorgonian Briareum violacea (depth of 15 m, Pingtung county, Taiwan, in May 2007). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μg/mL, InRt = (16.87 ± 4.86)%, p < 0.05, control Genistein, InRt = (65.05 ± 6.12)%, p < 0.01); anti-inflammatory (elastase release inhibitor, fMLP/CBinduced hmn neutrophils, 10 μg/mL, InRt = (6.40 ± 4.29)%), Genistein, InRt = (52.45 ± 6.34)%, p < 0.05). Ref: C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677 O O O O

O 14

1 10

O H O

O

OH O

O

1000 Briaviolide D Type: Briarane diterpenoids. C24H31ClO10 Colorless amorphous powder, [α]D24 = −6° (c = 0.1, CH2Cl2). Source: Gorgonian Briareum violacea (depth of 15 m, Pingtung county, Taiwan, in May 2007). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μg/mL, InRt = (4.48 ± 1.47)%, p < 0.05, control Genistein, InRt = (65.05 ± 6.12)%, p < 0.01); anti-inflammatory (elastase release inhibitor, fMLP/CBinduced hmn neutrophils, 10 μg/mL, InRt = (9.31 ± 6.64)%), Genistein, InRt = (52.45 ± 6.34)%, p < 0.05). Ref: C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677

3.18 Briarane diterpenoids

337

O O O 14

1 10

HO

HO

Cl

OH

H

O

O O

O

1001 Briaviolide E Type: Briarane diterpenoids. C29H39ClO11 Colorless amorphous powder, [α]D24 = −6° (c = 0.1, CH2Cl2). Source: Gorgonian Briareum violacea (depth of 15 m, Pingtung county, Taiwan, in May 2007). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μg/mL, InRt = (34.17 ± 0.79)%, p < 0.001, moderate, control Genistein, InRt = (65.05 ± 6.12)%, p < 0.01); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μg/mL, InRt = (26.03 ± 9.51)%), moderate, Genistein, InRt = (52.45 ± 6.34)%, p < 0.05). Ref: C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677 O O

O

O O

14

1 10

O H O O

Cl

OH O O

1002 Briaviolide F Type: Briarane diterpenoids. C28H39ClO10 Colorless amorphous gum, [α]D24 = +16° (c = 0.4, CH2Cl2). Source: Gorgonian Briareum violacea (depth of 15 m, Pingtung county, Taiwan, in May 2007). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μg/mL, InRt = (17.35 ± 6.91)%, control Genistein, InRt = (65.05 ± 6.12)%, p < 0.01); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μg/mL, InRt = (14.34 ± 5.28)%), Genistein, InRt = (52.45 ± 6.34)%, p < 0.05). Ref: C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677

338

3 Diterpenoids

OH

O

O O

14

1 10

O

Cl

OH

H

O

O O

O

1003 Briaviolide G Type: Briarane diterpenoids. C26H33ClO11 Colorless amorphous gum, [α]D24 = +18° (c = 0.6, CH2Cl2). Source: Gorgonian Briareum violacea (depth of 15 m, Pingtung county, Taiwan, in May 2007). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μg/mL, InRt = (3.25 ± 2.35)%, control Genistein, InRt = (65.05 ± 6.12)%, p < 0.01); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μg/mL, InRt = (16.66 ± 3.12)%), p < 0.01, Genistein, InRt = (52.45 ± 6.34)%, p < 0.05). Ref: C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677 O O

O

O O

14

1 10

O H O O

Cl

OH O O

1004 Briaviolide H Type: Briarane diterpenoids. C24H34O9 Colorless amorphous gum, [α]D24 = +53° (c = 0.2, CH2Cl2). Source: Gorgonian Briareum violacea (depth of 15 m, Pingtung county, Taiwan, in May 2007). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μg/mL, InRt = (6.01 ± 4.16)%, control Genistein, InRt = (65.05 ± 6.12)%, p < 0.01); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μg/mL, InRt = (18.78 ± 2.29)%), p < 0.01, Genistein, InRt = (52.45 ± 6.34)%, p < 0.05). Ref: C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677

3.18 Briarane diterpenoids

339

O

O O

O 14

1 10

HO

OH

H

O

OH

O

1005 Briaviolide I Type: Briarane diterpenoids. C24H34O10 Colorless amorphous powder, [α]D24 = +20° (c = 0.4, CH2Cl2). Source: Gorgonian Briareum violacea (depth of 15 m, Pingtung county, Taiwan, in May 2007). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μg/mL, InRt = (28.66 ± 1.99)%, moderate, p < 0.001, control Genistein, InRt = (65.05 ± 6.12)%, p < 0.01); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μg/mL, InRt = (28.81 ± 6.37)%), moderate, p < 0.05, Genistein, InRt = (52.45 ± 6.34)%, p < 0.05). Ref: C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677 O

O O

O 14

HO

1 10

O

OH

H OH

O O

1006 Briaviolide J Type: Briarane diterpenoids. C26H36O10 Colorless amorphous gum, [α]D24 = +50° (c = 0.1, CH2Cl2). Source: Gorgonian Briareum violacea (depth of 15 m, Pingtung county, Taiwan, in May 2007). Pharm: Anti-inflammatory (inhibitor of superoxide anion generation, 10 μg/mL, InRt = (11.64 ± 3.92)%, moderate, p < 0.05, control Genistein, InRt = (65.05 ± 6.12)%, p < 0.01); anti-inflammatory (elastase release inhibitor, fMLP/CB-induced hmn neutrophils, 10 μg/mL, InRt = (14.62 ± 4.41)%), moderate, p < 0.01, Genistein, InRt = (52.45 ± 6.34)%, p < 0.05). Ref: C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677

340

3 Diterpenoids

O

O O

O O

14

1 10

OH

O H

O

OH

O

1007 2,12-Diacetoxy-8,17-epoxy-9-hydroxy-5,13-briaradien-18,7-olide Type: Briarane diterpenoids. C24H32O8 Glass, [α]D = −44.9° (c = 0.31, CHCl3). Source: Gorgonians Briareum sp. DD6, Briareum excavatum (South Bay, Kenting, southernmost tip, Taiwan, depths of 4–5 m, July 1995). Pharm: Cytotoxic (P388, ED50 = 0.4 μg/ mL; HT29, ED50 = 1.1 μg/mL). Ref: B. F. Bowden, et al, Aust. J. Chem. 1989, 42, 1705│P. -J. Sung, et al, JNP, 2001, 64, 318 O O 3

O

1

13

10

O

H HO O

O O

1008 Dichotellide T Gemmacolide X Type: Briarane diterpenoids. C30H37ClO14 White amorphous powder. Source: Gorgonian Dichotella gemmacea (Meishan I., Hainan, China; Beihai, China). Pharm: Cytotoxic (A549, IC50 > 45.7 μmol/L, control Adriamycin, IC50 = 2.8 μmol/L; MG63, IC50 > 45.7 μmol/L, control Adriamycin, IC50 = 3.2 μmol/L). Ref: C. Li, et al, BoMCL,2012, 22, 4368│J. -F. Sun, et al, Tetrahedron, 2013, 69, 871 O

O

O

O O

O

O O

Cl O

H O

O O

O O

3.18 Briarane diterpenoids

341

1009 7,18:11,12-Diepoxy-2-(3-methylbutanoyl)-14-acetoxy-5,7,11, 17-briaratetraen-3-one Type: Briarane diterpenoids. C27H36O7 [α]D20 = −98.5° (c = 1.25, CCl4). Source: Octocorallia Pennatulacea (sea pen) Scytalium tentaculatum. Pharm: Increases cardiac output at high dose. Ref: B. N. Ravi, et al, Aust. J. Chem., 1980, 33, 2307

O

O

O O

O

2 11

12

O

H O

1010 Erythrolide A Type: Briarane diterpenoids. C26H31ClO10 Powder. Source: Gorgonian Erythropodium caribaeorum. Pharm: Antifeedant. Ref: S. A. Look, et al, JACS, 1984, 106, 5026│E. O. Pordesimo, et al, JOC, 1991, 56, 2344│R. J. Dookran, Nat. Prod., 1993, 56, 1051

O O O

4

O 9

O

OH

H O

Cl O

O O

1011 Excavatoid E Type: Briarane diterpenoids. C28H38O9 Powder, mp 192–193 °C, [α]D22 = +2°, (c = 0.15, CHCl3). Source: Gorgonian Briareum excavatum (cultivated specimen, Taiwan). Pharm: Elastase release inhibitor (hmn neutrophils, modest). Ref: P. -J. Sung, et al, Mar. Drugs, 2009, 7, 472

342

3 Diterpenoids

O

O

O

O O

O

2 14 9

H

O

OH

O

1012 Excavatoid F Type: Briarane diterpenoids. C28H38O12 Powder, mp 164–165 °C, [α]D25 = −16°, (c = 0.06, CHCl3). Source: Gorgonian Briareum excavatum (cultivated specimen, Taiwan). Pharm: Elastase release inhibitor (hmn neutrophils, modest). Ref: P. -J. Sung, et al, Mar. Drugs, 2009, 7, 472 O

O

O

O O

2

14

O

9

HO

H

O O

O

O

O

1013 Excavatoid O Type: Briarane diterpenoids. C30H42O13 White powder, mp 137–138 °C, [α]D25 = −39° (c = 0.4, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Anti-inflammatory (hmn neutrophils, 10 μg/mL, elastase release inhibitor, InRt = 16.9%). Ref: P. -J. Sung, et al, Bull. Chem. Soc. Jpn., 2010, 83, 539│J. -H. Su, et al, CPB, 2010, 58, 662│P. -J. Sung, et al, Mar. Drugs, 2010, 8, 2639 O

O

O O O

O

O HO

H O O

O O O

3.18 Briarane diterpenoids

343

1014 Excavatoid P Type: Briarane diterpenoids. C30H43ClO14 White powder, mp 154–155 °C, [α]D25 = +14° (c = 0.05, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Anti-inflammatory (hmn neutrophils, 10 μg/mL, elastase release inhibitor, InRt = 16.1%). Ref: P. -J. Sung, et al, Bull. Chem. Soc. Jpn., 2010, 83, 539│J. -H. Su, et al, CPB, 2010, 58, 662│P. -J. Sung, et al, Mar. Drugs, 2010, 8, 2639 O

O

O O OH O

O

OH Cl

HO

H OO

O O

O

1015 Excavatolide A 6-Chloro-4,8-epoxy-9-hydroxy-2,14-diacetoxy-5(16),11-briaradien-18,7-olide Type: Briarane diterpenoids. C24H31ClO8 Powder, mp > 290 °C, [α]D28 = +38° (c = 0.05, pyridine). Source: Gorgonian Briareum excavatum (Taiwan waters), gorgonian Briareum violacea (depth of 15 m, Pingtung county, Taiwan, in May 2007). Pharm: Cytotoxic (P388, ED50 > 50 μg/mL, KB, ED50 = 2.5 μg/mL, A549, ED50 = 21.9 μg/ mL, HT29, ED50 > 50 μg/mL). Ref: J. -H. Sheu, et al, JNP, 1998, 61, 602│C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677 O

O O

O

O Cl H OH

O O

1016 Excavatolide B Type: Briarane diterpenoids. C30H42O12 Cryst. (Me2CO), mp 224–225 °C, [α]D26 = −23° (c = 0.09, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 > 50 μg/mL, KB, ED50 > 50 μg/mL, A549, ED50 > 50 μg/mL, HT29, ED50 > 50 μg/mL). Ref: J. -H. Sheu, et al, JNP, 1998, 61, 602

344

3 Diterpenoids

O

O

O

O

O

O

HO H O O

O O

O

1017 Excavatolide C Type: Briarane diterpenoids. C28H38O12 Cryst., mp 134–135 °C, [α]D30 = −13° (c = 0.18, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 0.3 μg/mL, KB, ED50 = 1.9 μg/mL, A549, ED50 = 1.9 μg/mL, HT29, ED50 = 1.3 μg/mL). Ref: J. -H. Sheu, et al, JNP, 1998, 61, 602 O

O

O

O

O

O

HO H O O

O O

O

1018 Excavatolide D Type: Briarane diterpenoids. C26H36O11 Cryst., mp 235–237 °C, [α]D24 = +32° (c = 0.38, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 1.8 μg/mL, KB, ED50 = 4.2 μg/mL, A549, ED50 > 50 μg/mL, HT29, ED50 = 1.3 μg/mL). Ref: J. -H. Sheu, et al, JNP, 1998, 61, 602 O O OH

O

O

HO H O O

O O O

3.18 Briarane diterpenoids

345

1019 Excavatolide E Type: Briarane diterpenoids. C24H34O9 mp 190–191 °C, [α]D30 = +53° (c = 0.42, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 1.6 μg/mL, KB, ED50 = 0.8 μg/mL, A549, ED50 = 1.2 μg/mL, HT29, ED50 = 1.6 μg/mL). Ref: J. -H. Sheu, et al, JNP, 1998, 61, 602 O

O O

O

HO H HO O

O O

1020 Excavatolide F Type: Briarane diterpenoids. C30H40O11 Powder, mp 79–80 °C, [α]D27 = −28° (c = 1, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 6.2 μg/mL; KB, ED50 = 7.0 μg/mL; A549, ED50 = 5.2 μg/ mL; HT29, ED50 = 5.5 μg/mL，according to R. I. Geran, for significant activity ED50 ≤ 4.0 μg/mL is required). Ref: P. -J. Sung, et al, JNP, 1999, 62, 457 O

O O

O O O

H O O

O O O

1021 Excavatolide G Type: Briarane diterpenoids. C28H38O11 Powder, mp 219–220 °C, [α]D27 = +40° (c = 0.2, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 15.7 μg/mL; KB, ED50 > 50 μg/mL; A549, ED50 = 22.8 μg/mL; HT29, ED50 > 50 μg/mL). Ref: P. -J. Sung, et al, JNP, 1999, 62, 457

346

3 Diterpenoids

O

O O

O O O

H O

O O

O

O

1022 Excavatolide H Type: Briarane diterpenoids. C34H48O13 Solid, mp 189–190 °C, [α]D27 = +27° (c = 0.3, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 > 50 μg/mL; KB, ED50 > 50 μg/mL; A549, ED50 > 50 μg/mL; HT29, ED50 > 50 μg/mL). Ref: P. -J. Sung, et al, JNP, 1999, 62, 457 O

O

O

O O

O O O

H O

O O

O

O

1023 Excavatolide I Type: Briarane diterpenoids. C32H44O13 Solid, mp 225–227 °C, [α]D26 = +23° (c = 1, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 > 50 μg/mL; KB, ED50 > 50 μg/mL; A549, ED50 > 50 μg/mL; HT29, ED50 > 50 μg/mL). Ref: P. -J. Sung, et al, JNP, 1999, 62, 457 O

O

O

O O

O O O

H O O

O O O

3.18 Briarane diterpenoids

347

1024 Excavatolide J Type: Briarane diterpenoids. C32H44O13 Solid, mp 203–205 °C, [α]D26 = +38° (c = 0.6, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 3.8 μg/mL; KB, ED50 = 6.5 μg/mL; A549, ED50 = 5.2 μg/mL; HT29, ED50 = 5.2 μg/mL). Ref: P. -J. Sung, et al, JNP, 1999, 62, 457 O

O

O

O O

O O O

H O

O O

O

O

1025 Excavatolide K Type: Briarane diterpenoids. C30H44O13 Solid, mp 178–180 °C, [α]D26 = +35° (c = 0.7, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 0.9 μg/mL; KB, ED50 = 3.3 μg/mL; A549, ED50 = 3.0 μg/mL; HT29, ED50 = 1.3 μg/mL). Ref: P. -J. Sung, et al, JNP, 1999, 62, 457 O

O

O

O O

O O O

H O O

O O O

1026 Excavatolide M Type: Briarane diterpenoids. C24H34O10 Solid, mp 219–221 °C, [α]D26 = +74° (c = 0.6, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 0.001 μg/mL; KB, ED50 = 1.0 μg/mL; A549, ED50 = 0.1 μg/mL; HT29, ED50 = 2.2 μg/mL). Ref: P. -J. Sung, et al, JNP, 1999, 62, 457

348

3 Diterpenoids

O

O OHO

O

HO

H HO

O O O

1027 Excavatolide N Type: Briarane diterpenoids. C24H32O9 Cryst. (CHCl3/petrol), mp 239–240 °C, [α]D = +22° (c = 0.05, CHCl3). Source: Gorgonian Briareum excavatum (Western Australia). Pharm: Cytotoxic (P388, A549, HT29, MEL28, IC50 = 5 μg/mL, IC50 > 10 μg/mL, IC50 > 10 μg/mL, IC50 > 10 μg/mL respectively). Ref: J. E. Neve, et al, Aust. J. Chem., 1999, 52, 359 O

O O O

HO

H HO O

O O

1028 Excavatolide O Type: Briarane diterpenoids. C30H38O13 Cryst. (EtOH aq.), mp 193–195 °C, [α]D = −102° (c = 0.05, CHCl3). Source: Gorgonian Briareum excavatum (Western Australia). Pharm: Cytotoxic (P388, A549, HT29, MEL28, IC50 = 5 μg/mL, IC50 = 5 μg/mL, IC50 = 5 μg/mL, IC50 > 10 μg/mL respectively). Ref: J. E. Neve, et al, Aust. J. Chem., 1999, 52, 359 O O

O O

O O O

H O O O

O

O O

3.18 Briarane diterpenoids

349

1029 Excavatolide P Type: Briarane diterpenoids. C28H36O12 Amorph. powder, mp 94–96 °C, [α]D = +27° (c = 0.05, CHCl3). Source: Gorgonian Briareum excavatum (Western Australia). Pharm: Cytotoxic (P388, A549, HT29, MEL28, IC50 = 5 μg/mL, IC50 > 10 μg/mL, IC50 > 10 μg/mL, IC50 > 10 μg/mL respectively). Ref: J. E. Neve, et al, Aust. J. Chem., 1999, 52, 359 O

O

O

O O

O

O

H O O

O

O

O

1030 Excavatolide Q Type: Briarane diterpenoids. C24H30O9 Cryst. (EtOH), mp 212–214 °C, [α]D = −27° (c = 0.05, CHCl3). Source: Gorgonian Briareum excavatum (Western Australia). Pharm: Cytotoxic (P388, A549, HT29, MEL28, IC50 = 5 μg/mL, IC50 = 10 μg/mL, IC50 = 10 μg/ mL, IC50 = 10 μg/mL respectively). Ref: J. E. Neve, et al, Aust. J. Chem., 1999, 52, 359 O

O O O

O

H HO O

O O

1031 Excavatolide V Type: Briarane diterpenoids. C32H42O13 Powder, mp 183–185 °C, [α]D25 = +40° (c = 0.6, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 3.9 μg/mL; KB, ED50 = 7.0 μg/mL; A549, ED50 = 19.1 μg/mL; HT29, ED50 = 20.4 μg/mL). Ref: J. -H. Sheu, et al, JNP, 1999, 62, 1415

350

3 Diterpenoids

O

O

O

O O

O O O

H O

O O

O

O

1032 Excavatolide W Type: Briarane diterpenoids. C29H40O11 Amorph. solid, mp 222–224 °C, [α]D25 = +53° (c = 0.8, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 19.4 μg/mL; KB, ED50 > 50 μg/mL; A549, ED50 > 50 μg/mL; HT29, ED50 > 50 μg/mL). Ref: P. -J. Sung, et al, JNP, 1999, 62, 457│J. -H. Sheu, et al, JNP, 1999, 62, 1415 O

O O

O O O

H O O

O

O

O

1033 Excavatolide Y Type: Briarane diterpenoids. C27H36O11 Solid, mp 147–148 °C, [α]D27 = −71° (c = 0.4, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 9.5 μg/mL; KB, ED50 > 50 μg/mL; A549, ED50 > 50 μg/mL; HT29, ED50 = 15.1 μg/mL). Ref: J. -H. Sheu, et al, JNP, 1999, 62, 1415 O

O O

O

O O HO

H HO O

O O

3.18 Briarane diterpenoids

351

1034 Excavatolide Z Type: Briarane diterpenoids. C28H40O11 Powder, mp 257–259 °C, [α]D25 = +22° (c = 0.5, CHCl3). Source: Gorgonian Briareum excavatum (Taiwan waters). Pharm: Cytotoxic (P388, ED50 = 1.3 μg/mL; KB, ED50 = 6.5 μg/mL; A549, ED50 = 11.2 μg/mL; HT29, ED50 = 2.8 μg/mL). Ref: J. -H. Sheu, et al, JNP, 1999, 62, 1415 O

O O

O O O HO

H HO

O O O

1035 Fragilide C Type: Briarane diterpenoids. C27H35ClO11 Powder, mp 274–275 °C, [α]D25 = +28° (c = 0.05, CHCl3). Source: Gorgonian Junceella fragilis (Taiwan waters). Pharm: Antiinflammatory (weak). Ref: P. -J. Sung, et al, Tetrahedron, 2008, 64, 2596│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

O

OH

15 2

14

1

11

10

20

O

Cl

9

H

O

16

O

O

17 18

O 19

O

1036 Fragilide E Type: Briarane diterpenoids. C28H37ClO13 Cryst., mp 143–144 °C, [α]D25 = +13° (c = 0.05, CHCl3). Source: Gorgonian Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory (weak). Ref: P. -J. Sung, et al, Chem. Lett., 2009, 38, 454│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)

352

3 Diterpenoids

O

O

O

O

O

O

15 2

14

1

11

10

O

16

O Cl

9

OH

O

H O

OH

17 19 18

O

1037 12-epi-Fragilide G Gemmacolide H Type: Briarane diterpenoids. C28H35ClO12 White amorphous powder (MeOH), [α]D24 = +6° (c = 0.20, CHCl3). Source: Gorgonian Ellisella robusta (Taiwan; South China Sea). Pharm: Cytotoxic (A549, IC50 = 47.3 μmol/L; MG63, IC50 = 54.0 μmol/L). Ref: Y. -C. Chang, et al, Heterocycles, 2010, 81, 991│C. Li, et al, JNP, 2011, 74, 1658 O

O O

O O 12

O

OH

O

Cl

H O

O O

O

1038 Fragilide J Type: Briarane diterpenoids. C26H33ClO11 Source: Gorgonian Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory (weak). Ref: S. -H. Wang, et al, CPB, 2010, 58, 928│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O O OH

O

O

15 16

2 14

1

11

10

O Cl

9

H

O

20

O

O 17 19

O

18

O

3.18 Briarane diterpenoids

353

1039 Frajunolide A Type: Briarane diterpenoids. C28H38O11 Amorph. powder, [α]D26 = −87.8° (c = 1, CH2Cl2). Source: Gorgonian Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory (weak). Ref: Y. -C. Shen, et al, Helv. Chim. Acta, 2007, 90, 1391│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

O

15 16

2

O

14

1

11

10

O

9

OH

H 20

O

O

17 19

O

18

O

1040 Frajunolide B Type: Briarane diterpenoids. C30H40O13 Amorph. powder, [α]D26 = −12.7° (c = 1, CH2Cl2). Source: Gorgonian Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory (superoxide anion O2•− generation and elastase release by hmn neutrophils, IC50 > 10 μg/mL, MMOA: superoxide anion and elastase inhibition). Ref: Y. -C. Shen, et al, Helv. Chim. Acta, 2007, 90, 1391│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

O

O

O

15

O

16

2 14

1

11

10

O

OH 9

H 20

O

O 17 19

O

18

O

1041 Frajunolide C Type: Briarane diterpenoids. C28H35ClO12 Amorph. powder, [α]D26 = −13.2° (c = 0.4, CH2Cl2). Source: Gorgonian Junceella fragilis (Taiwan waters). Pharm: Antiinflammatory (superoxide anion O2•− generation and elastase release by hmn neutrophils, IC50 > 10 μg/mL, MMOA: superoxide anion and elastase inhibition). Ref: Y. -C. Shen, et al, Helv. Chim. Acta, 2007, 90, 1391│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)

354

3 Diterpenoids

O

O O

O

15 16

2

O O

14

1

11

10

Cl OH

9

O

H 20

O

O

17 19

O

18

O

1042 Frajunolide E Type: Briarane diterpenoids. C28H38O11 Amorph. powder, [α]D24 = −242° (c = 0.4, CH2Cl2). Source: Gorgonian Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory (weak). Ref: C. -C. Liaw, et al, JNP, 2008, 71, 1551│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

O

15

O

16

2

O

14

1

11

10

OH

9

H 20

O

O 17 19

O

18

O

1043 Frajunolide F Type: Briarane diterpenoids. C28H35ClO12 Amorph. powder, mp 188–194 °C, [α]D24 = −18.3° (c = 0.6, CH2Cl2). Source: Gorgonian Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory (weak). Ref: C. -C. Liaw, et al, JNP, 2008, 71, 1551│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

O O O

OH

15 16

2 14

1

11

10

H 20

O Cl

9

O

O 17 19

O

18

O

3.18 Briarane diterpenoids

355

1044 Frajunolide I Type: Briarane diterpenoids. C28H35ClO12 Amorph. powder, mp 172–175 °C, [α]D24 = −1.6° (c = 0.1, CH2Cl2). Source: Gorgonian Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory (weak). Ref: C. -C. Liaw, et al, JNP, 2008, 71, 1551│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

15

O

O

2 14 11

O

20

OH

9

H

O

16

1 10

O

Cl O

17

O

19

18

O

1045 Frajunolide J Type: Briarane diterpenoids. C29H40O11 Amorph. powder, [α]D24 = −96.6° (c = 0.3, CH2Cl2). Source: Gorgonian Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory (weak). Ref: C. -C. Liaw, et al, JNP, 2008, 71, 1551│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

O

15 16

2

O

14

1

11

10

O

9

H 20

O

OH O 17 19

O

18

O

1046 Frajunolide L Type: Briarane diterpenoids. C28H38O11 Colorless amorphous gum, [α]D24 = + 6.0° (c = 0.2, CH2Cl2). Source: Gorgonian Junceella fragilis (Taitung county, Taiwan). Pharm: Anti-inflammatory (hmn neutrophils in response to fMLP/CB, 10 μg/mL: Superoxide anion O2•− generation, InRt = (18.7 ± 2.6)% (P < 0.01), control Genistein, InRt = (65.0 ± 5.7)%; Elastase release InRt = (16.2 ± 0.7)% (P < 0.001), control Genistein, InRt = (51.6 ± 5.9)%). Ref: C. -C. Liaw, et al, Mar. Drugs, 2011, 9, 1477

356

3 Diterpenoids

O

O O

O O

OH

O

H O

O O

O

1047 Frajunolide M Type: Briarane diterpenoids. C28H38O18 Colorless amorphous powder, [α]D24 = +8.0° (c = 0.2, CH2Cl2). Source: Gorgonian Junceella fragilis (Taitung county, Taiwan). Pharm: Anti-inflammatory (hmn neutrophils in response to fMLP/ CB, 10 μg/mL: Superoxide anion O2•− generation, InRt = (2.0 ± 2.3)%; control Genistein, InRt = (65.0 ± 5.7)%; Elastase release InRt = (13.3 ± 3.1)% (P < 0.05), control Genistein, InRt = (51.6 ± 5.9)%). Ref: C. -C. Liaw, et al, Mar. Drugs, 2011, 9, 1477 O

O O

O

OH

O O

H O

O O

O

1048 Frajunolide N Type: Briarane diterpenoids. C28H37ClO12 Colorless amorphous powder, [α]D24 = +18° (c = 0.1, CH2Cl2). Source: Gorgonian Junceella fragilis (Taitung county, Taiwan). Pharm: Anti-inflammatory (hmn neutrophils in response to fMLP/CB, 10 μg/mL: Superoxide anion O2•− generation, InRt = (0.6 ± 1.5)%; control Genistein, InRt = (65.0 ± 5.7)%; Elastase release InRt = (22.3 ± 7.7)%, control Genistein, InRt = (51.6 ± 5.9)%). Ref: C. -C. Liaw, et al, Mar. Drugs, 2011, 9, 1477

3.18 Briarane diterpenoids

O

O

O

O

O

O

OH O

357

Cl

H O

O O

O

1049 Frajunolide O Nuiinoalide C Type: Briarane diterpenoids. C28H37ClO11 Colorless amorphous powder, [α]D24 = +6.7° (c = 0.7, CH2Cl2); Solid, [α]D = +29° (c = 0.4, CHCl3). Source: Gorgonian Junceella fragilis (Taitung county, Taiwan), an octocoral. Pharm: Anti-inflammatory (hmn neutrophils in response to fMLP/CB, 10 μg/mL: Superoxide anion O2• − generation, InRt = (8.3 ± 3.6)%; control Genistein, InRt = (65.0 ± 5.7)%; Elastase release InRt = (17.2 ± 6.7)% (P < 0.05), control Genistein, InRt = (51.6 ± 5.9)%). Ref: M. T. Hamann, et al, Heterocycles, 1996, 42, 325│C. -C. Liaw, et al, Mar. Drugs, 2011, 9, 1477│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

O

15

O O

16

2 14

1

11

10 9

OH

Cl

H 20

O

O 17 19

O

18

O

1050 Funicolide A Type: Briarane diterpenoids. C25H34O6 [α]D20 = +33.2° (c = 0.6, EtOH). Source: Sea pen Funiculina quadrangularis (Mediterranean Sea). Pharm: Antiviral; anti-inflammatory. Ref: A. Guerriero, et al, Helv. Chim. Acta, 1995, 78, 1465│G. Chiasera, et al, Helv. Chim. Acta, 1995, 78, 1479

358

3 Diterpenoids

O

O O

O

15 2

14

1

11

10

16

9

H 20

17 18

O 19

O

1051 7-epi-Funicolide A Type: Briarane diterpenoids. C24H34O6 [α]D20 = −43.4° (c = 0.14, EtOH). Source: Sea pen Funiculina quadrangularis (Mediterranean Sea). Pharm: Antiviral; anti-inflammatory. Ref: A. Guerriero, et al, Helv. Chim. Acta, 1995, 78, 1465│G. Chiasera, et al, Helv. Chim. Acta, 1995, 78, 1479 O

O O

O

15 2

14

1

11

10

16

9

H 20

O 17 18

19

O

1052 Funicolide B Type: Briarane diterpenoids. C25H34O7 [α]D20 = −45.7° (c = 0.14, EtOH). Source: Sea pen Funiculina quadrangularis (Mediterranean Sea). Pharm: Antiviral; anti-inflammatory. Ref: A. Guerriero, et al, Helv. Chim. Acta, 1995, 78, 1465│G. Chiasera, et al, Helv. Chim. Acta, 1995, 78, 1479 O

O O

O

15 2

14

1

11

10

H

16

9

OH

20

O 17 19 18

O

3.18 Briarane diterpenoids

359

1053 Funicolide C Type: Briarane diterpenoids. C27H36O8 [α]D20 = +69.4° (c = 0.31, EtOH). Source: Sea pen Funiculina quadrangularis (Mediterranean Sea). Pharm: Antiviral; anti-inflammatory. Ref: A. Guerriero, et al, Helv. Chim. Acta, 1995, 78, 1465│G. Chiasera, et al, Helv. Chim. Acta, 1995, 78, 1479 O

O O

O

15 2

14

1

11

10 9

H 20

16

O

O

O 17 18

19

O

1054 Funicolide D Type: Briarane diterpenoids. C26H36O6 [α]D20 = +33.2° (c = 0.25, EtOH). Source: Sea pen Funiculina quadrangularis (Mediterranean Sea). Pharm: Antiviral; anti-inflammatory. Ref: A. Guerriero, et al, Helv. Chim. Acta, 1995, 78, 1465│G. Chiasera, et al, Helv. Chim. Acta, 1995, 78, 1479 O

O O

O

15 2

14

1

11

10

H

16

9

20

O 17 18

19

O

1055 Funicolide E Type: Briarane diterpenoids. C24H32O7 [α]D20 = −61.7° (c = 0.59, EtOH). Source: Sea pen Funiculina quadrangularis (Mediterranean Sea). Pharm: Antiviral; anti-inflammatory. Ref: A. Guerriero, et al, Helv. Chim. Acta, 1995, 78, 1465│G. Chiasera, et al, Helv. Chim. Acta, 1995, 78, 1479

360

3 Diterpenoids

O

O O

O

15 2

14

1

11

10

H

16

9

OH

20

O

17

19

18

O

1056 Gemmacolide B Type: Briarane diterpenoids. C33H45ClO14 Oil, [α]D = −5.5° (c = 0.44, CHCl3). Source: Gorgonians Junceella juncea (South China Sea),Junceella juncea (Indian Ocean, Tuticorin coast) and Junceella gemmacea (Federated States of Micronesia). Pharm: Immunomodulator, insecticide. Ref: H. -Y. He, et al, Tetrahedron, 1991, 47, 3271│A. S. R. Anjaneyulu, et al, JCS Perkin I, 1997, 959│A. S. R. Anjaneyulu, et al, JNP, 2003, 66, 507│S. -H. Qi, et al, Chem. Nat. Comp., 2009, 45, 49│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

O

15

O O

O

O

16

2 14

1

11

10 9

OH

Cl

H

O 20

O

O 17 19

O

18

O

1057 (+)-Gemmacolide B Type: Briarane diterpenoids. C33H45ClO14 Cryst. (hexane/CHCl3), mp 298–230 °C, [α]D25 = +5.3° (c = 0.44, CHCl3). Source: Gorgonian Junceella juncea (Indian Ocean). Pharm: Immunomodulator; insecticide. Ref: A. S. R. Anjaneyulu,et al, Pallas. J. Chem. Soc., Perkin Trans 1, 1997, 959│P. -J. Sung, et al, Biochemical Systematics and Ecology, 2004, 32, 185 (rev)

3.18 Briarane diterpenoids

O

O O

O

O

O

15

O

16

2

O

361

14

1

11

10

OH

9

Cl

H

O 20

O

O 18

19

17

O

O

1058 Gemmacolide D Type: Briarane diterpenoids. C28H35ClO13 Oil, [α]D = +88.3° (c = 0.66, CHCl3). Source: Gorgonian Junceella gemmacea (Pohnpei I., Federated States of Micronesia) (Federated States of Micronesia). Pharm: Immunomodulator. Ref: H. He, et al, Tetrahedron, 1991, 47, 3271│P. -J. Sung, et al, Biochemical Systematics and Ecology, 2004, 32, 185 (rev) O

O O

O

O O

2

3Z

14 12

HO

9

O

OH

Cl

H O

O O

O

1059 Gemmacolide G Type: Briarane diterpenoids. C30H37ClO14 White amorphous powder (MeOH), [α]D24 = 0° (c = 0.10, CHCl3). Source: Gorgonian Dichotella gemmacea (South China Sea). Pharm: Cytotoxic (A549, IC50 = 8.4 μmol/L; MG63, IC50 = 38.4 μmol/L). Ref: C. Li, et al, JNP, 2011, 74, 1658 O

O O

O O

15

O O

2

O O

14

1

11

10

H 20

O

9

O

16

OH

Cl O

17 18

19

O

362

3 Diterpenoids

1060 Gemmacolide I Type: Briarane diterpenoids. C31H41ClO12 White amorphous powder (MeOH), [α]D24 = 0° (c = 0.17, CHCl3). Source: Gorgonian Dichotella gemmacea (South China Sea). Pharm: Cytotoxic (A549, IC50 = 20.6 μmol/L; MG63, IC50 = 25.0 μmol/L). Ref: C. Li, et al, JNP, 2011, 74, 1658 O

O O

O

15 2

O

14

1

11

10

O

20

OH

9

H

O

16

Cl O

O

17

O

19

18

O

1061 Gemmacolide J Type: Briarane diterpenoids. C33H43ClO14 White amorphous powder (MeOH), [α]D24 = 0° (c = 0.04, CHCl3). Source: Gorgonian Dichotella gemmacea (South China Sea). Pharm: Cytotoxic (A549, IC50 < 1.4 μmol/L; MG63, IC50 = 79.8 μmol/L); antibacterial (Bacillus megaterium); antifungal (Septoria tritici). Ref: C. Li, et al, JNP, 2011, 74, 1658 O

O O

O

15

O O

O

2 14

1

11

10 9

OH

Cl

H

O O

16

20

O

O 17 19

O

18

O

1062 Gemmacolide K Type: Briarane diterpenoids. C33H43ClO15 White amorphous powder (MeOH), [α]D24 = −79° (c = 0.17, CHCl3). Source: Gorgonian Dichotella gemmacea (South China Sea). Pharm: Cytotoxic (A549, IC50 = 38.2 μmol/L; MG63, IC50 = 45.9 μmol/L). Ref: C. Li, et al, JNP, 2011, 74, 1658

3.18 Briarane diterpenoids

363

O

O

OH

O

O O O

O

OH

Cl

H

O

O

O

O O

O

1063 Gemmacolide M Type: Briarane diterpenoids. C34H46O15 White amorphous powder (MeOH), [α]D24 = −148° (c = 0.28, CHCl3). Source: Gorgonian Dichotella gemmacea (South China Sea). Pharm: Antibacterial (Bacillus megaterium); antifungal (Septoria tritici). Ref: C. Li, et al, JNP, 2011, 74, 1658 O

O O

O O O

O

OH O

O

H O

O O

O O

1064 Gemmacolide N Type: Briarane diterpenoids. C29H38O13 White amorphous powder, [α]D24 = 0° (c = 0.035, CHCl3). Source: Gorgonian Dichotella gemmacea (South China Sea). Pharm: Cytotoxic (A549, IC50 > 50.5 μmol/L, control Adriamycin, IC50 = (2.8 ± 0.32) μmol/ L; MG63, IC50 > 50.5 μmol/L, Adriamycin, IC50 = (3.2 ± 0.37)μmol/L); antifungal (Agar diffusion assay, 0.05 mg, Microbotryum violaceum, IZR = 0 mm, control Penicillin, IZR = 7.0 mm; Septoria tritici,IZR = 7.5 mm, Penicillin, IZR = 6.0 mm); antibacterial (Agar diffusion assay, 0.05 mg, Escherichia coli,IZR = 12.5 mm, control Penicillin, IZR = 15.0 mm; Bacillus megaterium, IZR = 0 mm, Penicillin, IZR = 8.0 mm). Ref: C. Li, et al, JNP, 2011, 74, 1658│C. Li, et al, Mar. Drugs, 2011, 9, 1403

364

3 Diterpenoids

O

O O

O

O

O O

OH H

O

O

O O

O

1065 Gemmacolide O Type: Briarane diterpenoids. C30H37ClO15 White amorphous powder, [α]D24 = −30° (c = 0.04, CHCl3). Source: Gorgonian Dichotella gemmacea (South China Sea). Pharm: Cytotoxic (A549, IC50 > 44.6 μmol/L, control Adriamycin, IC50 = (2.8 ± 0.32)μmol/L; MG63, IC50 > 44.6 μmol/L, Adriamycin, IC50 = (3.2 ± 0.37)μmol/L); antifungal (Agar diffusion assay, 0.05 mg, Microbotryum violaceum, IZR = 6.0 mm, control Penicillin, IZR = 7.0 mm; Septoria tritici,IZR = 6.5 mm, Penicillin, IZR = 6.0 mm); antibacterial (Agar diffusion assay, 0.05 mg, Escherichia coli,IZR = 13.0 mm, control Penicillin, IZR = 15.0 mm; Bacillus megaterium, IZR = 6.0 mm, Penicillin, IZR = 8.0 mm). Ref: C. Li, et al, JNP, 2011, 74, 1658│C. Li, et al, Mar. Drugs, 2011, 9, 1403 O

O O O

OH

O

O O O

Cl OH O

H O O

O O

1066 Gemmacolide P Type: Briarane diterpenoids. C33H44O15 White amorphous powder, [α]D24 = −16° (c = 0.08, CHCl3). Source: Gorgonian Dichotella gemmacea (South China Sea). Pharm: Cytotoxic (A549, IC50 > 44.1 μmol/L, control Adriamycin, IC50 = (2.8 ± 0.32) μmol/L; MG63, IC50 > 44.1 μmol/L, Adriamycin, IC50 = (3.2 ± 0.37)μmol/L); antifungal (Agar diffusion assay, 0.05 mg, Microbotryum violaceum, IZR = 6.0 mm, control Penicillin, IZR = 7.0 mm; Septoria tritici,IZR = 6.5 mm, Penicillin, IZR = 6.0 mm); antibacterial (Agar diffusion assay, 0.05 mg, Escherichia coli,IZR = 7.5 mm, control Penicillin, IZR = 15.0 mm; Bacillus megaterium, IZR = 5.5 mm, Penicillin, IZR = 8.0 mm). Ref: C. Li, et al, JNP, 2011, 74, 1658│C. Li, et al, Mar. Drugs, 2011, 9, 1403

3.18 Briarane diterpenoids

O

O O O

O

O O O

365

OH OH H

O

O

O O

O

1067 Gemmacolide Q Type: Briarane diterpenoids. C33H44O16 White amorphous powder, [α]D24 = −17° (c = 0.065, CHCl3). Source: Gorgonian Dichotella gemmacea (South China Sea). Pharm: Cytotoxic (A549, IC50 = (21.6 ± 1.8)μmol/L, control Adriamycin, IC50 = (2.8 ± 0.32)μmol/L; MG63, IC50 = (20.5 ± 2.1)μmol/L, Adriamycin, IC50 = (3.2 ± 0.37)μmol/L); antifungal (Agar diffusion assay, 0.05 mg, Microbotryum violaceum, IZR = 6.5 mm, control Penicillin, IZR = 7.0 mm; Septoria tritici,IZR = 7.5 mm, Penicillin, IZR = 6.0 mm); antibacterial (Agar diffusion assay, 0.05 mg, Escherichia coli,IZR = 10.0 mm, control Penicillin, IZR = 15.0 mm; Bacillus megaterium, IZR = 5.5 mm, Penicillin, IZR = 8.0 mm). Ref: C. Li, et al, JNP, 2011, 74, 1658│C. Li, et al, Mar. Drugs, 2011, 9, 1403 O

O O O

OH

O

O O O

OH OH O

H O O

O O

1068 Gemmacolide R Type: Briarane diterpenoids. C33H44O16 White amorphous powder, [α]D24 = −18° (c = 0.05, CHCl3). Source: Gorgonian Dichotella gemmacea (South China Sea). Pharm: Cytotoxic (A549, IC50 = (27.2 ± 2.4)μmol/L, control Adriamycin, IC50 = (2.8 ± 0.32) μmol/L; MG63, IC50 = (23.7 ± 2.8)μmol/L, Adriamycin, IC50 = (3.2 ± 0.37)μmol/L); antifungal (Agar diffusion assay, 0.05 mg, Microbotryum violaceum, IZR = 0 mm, control Penicillin, IZR = 7.0 mm; Septoria tritici,IZR = 5.5 mm, Penicillin, IZR = 6.0 mm); antibacterial (Agar diffusion assay, 0.05 mg, Escherichia coli,IZR = 5.5 mm, control Penicillin, IZR = 15.0 mm; Bacillus megaterium, IZR = 6.0 mm, Penicillin, IZR = 8.0 mm). Ref: C. Li, et al, JNP, 2011, 74, 1658│C. Li, et al, Mar. Drugs, 2011, 9, 1403

366

3 Diterpenoids

O

O O O

OH

O

O O O

OH OH H

O

O

O O

O

1069 Gemmacolide S Type: Briarane diterpenoids. C43H60O18 White amorphous powder, [α]D24 = −71° (c = 0.055, CHCl3). Source: Gorgonian Dichotella gemmacea (South China Sea). Pharm: Cytotoxic (A549, IC50 = (16.4 ± 2.3)μmol/L, control Adriamycin, IC50 = (2.8 ± 0.32)μmol/L; MG63, IC50 = (18.8 ± 3.9)μmol/L, Adriamycin, IC50 = (3.2 ± 0.37)μmol/L); antifungal (Agar diffusion assay, 0.05 mg, Microbotryum violaceum, IZR = 7.0 mm, control Penicillin, IZR = 7.0 mm; Septoria tritici,IZR = 0 mm, Penicillin, IZR = 6.0 mm); antibacterial (Agar diffusion assay, 0.05 mg, Escherichia coli,IZR = 6.0 mm, control Penicillin, IZR = 15.0 mm; Bacillus megaterium, IZR = 0 mm, Penicillin, IZR = 8.0 mm). Ref: C. Li, et al, JNP, 2011, 74, 1658│C. Li, et al, Mar. Drugs, 2011, 9, 1403 O

O O O

O

O

O

O

O O

O OH O

O

H O O

O O

1070 Gemmacolide T Type: Briarane diterpenoids. C33H45ClO14 White amorphous powder. Source: Gorgonian Dichotella gemmacea (Beibuwan Bay, Guangxi, China). Pharm: Cytotoxic (A549, IC50 = 16.9 μmol/L, control Adriamycin, IC50 = 2.8 μmol/L; MG63, IC50 = 18.0 μmol/L, control Adriamycin, IC50 = 3.2 μmol/L). Ref: C. Li, et al, BoMCL,2012, 22, 4368

3.18 Briarane diterpenoids

O

O

O

O

O

367

O

O OH

O

Cl

H

O

O

O O

O

1071 Gemmacolide U Type: Briarane diterpenoids. C33H45ClO14 White amorphous powder. Source: Gorgonian Dichotella gemmacea (Beibuwan Bay, Guangxi, China). Pharm: Cytotoxic (A549, IC50 = 18.0 μmol/L, control Adriamycin, IC50 = 2.8 μmol/L; MG63, IC50 = 15.1 μmol/L, control Adriamycin, IC50 = 3.2 μmol/L). Ref: C. Li, et al, BoMCL,2012, 22, 4368 O

O O

O

O O

O OH

O O

H

Cl O

O O

O

1072 Gemmacolide V Type: Briarane diterpenoids. C30H39ClO14 White amorphous powder. Source: Gorgonian Dichotella gemmacea (Beibuwan Bay, Guangxi, China). Pharm: Cytotoxic (A549, IC50 < 1.5 μmol/L, control Adriamycin, IC50 = 2.8 μmol/L; MG63, IC50 = 20.5 μmol/L, control Adriamycin, IC50 = 3.2 μmol/L). Ref: C. Li, et al, BoMCL,2012, 22, 4368 O

O O

O

O O

O OH

O O

Cl

H O O

O O

368

3 Diterpenoids

1073 Gemmacolide W Type: Briarane diterpenoids. C38H53ClO16 White amorphous powder. Source: Gorgonian Dichotella gemmacea (Beibuwan Bay, Guangxi, China). Pharm: Cytotoxic (A549, IC50 = 19.1 μmol/L, control Adriamycin, IC50 = 2.8 μmol/L; MG63, IC50 = 17.4 μmol/L, control Adriamycin, IC50 = 3.2 μmol/L). Ref: C. Li, et al, BoMCL,2012, 22, 4368 O

O O O

O

O

O

O

O OH

O

Cl

H

O

O

O O

O

1074 Gemmacolide Y Type: Briarane diterpenoids. C33H43ClO14 White amorphous powder. Source: Gorgonian Dichotella gemmacea (Beibuwan Bay, Guangxi, China). Pharm: Cytotoxic (A549, IC50 < 0.3 μmol/L, control Adriamycin, IC50 = 2.8 μmol/L; MG63, IC50 < 0.3 μmol/L, control Adriamycin, IC50 = 3.2 μmol/L). Ref: C. Li, et al, BoMCL,2012, 22, 4368 O

O

O

O O

O O

O Cl

O O

H O O

O O

1075 Junceellolide A Type: Briarane diterpenoids. C26H33ClO10 Cryst., mp 115–116 °C, [α]D = −7.9° (c = 0.6, CHCl3). Source: Gorgonians Junceella fragilis (Pass Reef of Madang, Papua New Guinea), Junceella fragilis (South China Sea), Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory. Ref: J. Shin, et al, Tetrahedron, 1989, 45, 1633│D. J. Faulkner, 1991, NPR, 8, 97│P. -J. Sung, et al, Heterocycles, 2002, 57, 535│P. -J. Sung, et al, Biochemical Systematics and Ecology, 2004, 32, 185 (rev)│N. K. Kubota, et al, Bull. Chem. Soc. Jpn., 2006, 79, 634│C. -C. Liaw, et al, JNP, 2008, 71, 1551│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)

3.18 Briarane diterpenoids

369

O

O O

15

O

OH 2

14

1

11

10

16

O Cl

9

H

20

O

17

O 19

18

O

O

1076 Junceellolide B (2β,3E,6α,7α,8α,9β,14α)-6-Chloro-2,9,14-trihydroxy-8-hydroxy-3,5(16),11(20)-briaratrien-18,7-olide Type: Briarane diterpenoids. C26H33ClO9 Cryst., mp 95–96 °C, [α]D = +9.4° (c = 1.3, CHCl3). Source: Gorgonians Junceella fragilis (Pass Reef of Madang, Papua New Guinea), Junceella fragilis (South China Sea), Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory; phospholipase A inhibitor. Ref: J. Shin, et al, Tetrahedron, 1989, 45, 1633│P. -J. Sung, et al, Heterocycles 57, 2002, 535│P. -J. Sung, et al, Biochemical Systematics and Ecology, 2004, 32, 185 (rev)│N. K. Kubota, et al, Bull. Chem. Soc. Jpn., 2006, 79, 634│C. -C. Liaw, et al, JNP, 2008, 71, 1551│P. -J. Sung, et al, CPB, 2008, 56, 1276│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

15

O 3E 2

14

1

11

10 9

20

16

Cl

OH

H O 18

O

17

O 19

O

1077 Junceellolide C Robustolide J Type: Briarane diterpenoids. C26H33ClO10 Cryst. or powder, mp 120–125 °C, mp 99–101 °C, [α]D = +36.1° (c = 1.2, CHCl3), [α]D25 = −11° (c = 0.05, CHCl3). Source: Gorgonians Junceella fragilis (South China Sea), Junceella fragilis (Taiwan waters), Junceella juncea and Ellisella robusta. Pharm: Anti-inflammatory; phospholipase A inhibitor; phospholipase A2 inhibitor. Ref: J. Shin, et al, Tetrahedron, 1989, 45, 1633│P. -J. Sung, et al, Heterocycles, 2002, 57, 535│C. Tanaka, et al, JNP, 2004, 67, 1368│P. -J. Sung, et al, Biochemical Systematics and Ecology, 2004, 32, 185 (rev)│T. -L. Hwang, et al, Bull. Chem. Soc. Jpn., 2008, 81,

370

3 Diterpenoids

1638│C. -C. Liaw, et al, JNP, 2008, 71, 1551│P. -J. Sung, et al, CPB, 2008, 56, 1276│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)│C. Li, et al, BoMCL, 2012, 22, 4368 O

O O

15

O 3E 2

14

1

11

10 9

H

O 20

O

16

Cl

OH O

17

19

18

O

O

1078 Junceellolide D Type: Briarane diterpenoids. C28H38O11 Cryst., mp 208–209 °C, [α]D = −7.7° (c = 2.5, CHCl3). Source: Gorgonians Junceella fragilis (Pass Reef of Madang, Papua New Guinea), Junceella fragilis (South China Sea), Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory; phospholipase A inhibitor; phospholipase A2 inhibitor. Ref: J. Shin, et al, Tetrahedron, 1989, 45, 1633│P. -J. Sung, et al, Heterocycles, 2002, 57, 535│P. -J. Sung, et al, Biochemical Systematics and Ecology, 2004, 32, 185 (rev)│N. K. Kubota, et al, Bull. Chem. Soc. Jpn., 2006, 79, 634│C. -C. Liaw, et al, JNP, 2008, 71, 1551│S. -H. Qi, et al, Chem. Nat. Comp., 2009, 45, 49│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

15

O O

O 2

14

1

11

10 9

20

16

OH

H O 18

O

17

O 19

O

1079 Junceellolide K Type: Briarane diterpenoids. C26H36O10 Powder, mp 265–268 °C, [α]D25 = −28° (c = 0.3, CHCl3). Source: Gorgonian Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory (weak). Ref: J. -H. Sheu, et al, JNP, 2006, 69, 269│C. -C. Liaw, et al, JNP, 2008, 71, 1551│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)

3.18 Briarane diterpenoids

371

O

O O

O

15 16

2 14

1

11

10

O

OH

9

H 20

O

17

O 19

O

18

O

1080 Junceellonoid C Type: Briarane diterpenoids. C24H31ClO10 Powder, [α]D = −67.6° (c = 0.05, Py). Source: Gorgonian Junceella fragilis (South China Sea). Pharm: Cytotoxic (tMDAMB-231 and MCF7, 100 μmol/L). Ref: S. -H. Qi, et al, Helv. Chim. Acta 2005, 88, 2349│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O O

15

OH

OH

2 14

16

1

O

10

11

Cl

9

H

O

20

O

O

17

19

18

O

O

1081 Junceellonoid D Type: Briarane diterpenoids. C24H31ClO9 Powder, [α]D = −44.8° (c = 0.1, MeOH/ CHCl3). Source: Gorgonians Junceella fragilis (South China Sea) and Junceella fragilis (Taiwan waters). Pharm: Cytotoxic (tMDA-MB-231 and MCF7, 100 μmol/L). Ref: S. -H. Qi, et al, Helv. Chim. Acta 2005, 88, 2349│P. -J. Sung, et al, Bull. Chem. Soc. Jpn., 2009, 82, 1426│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O O

15

OH

OH

2 14

1

11

10

H

20

Cl

9

O 18

O

16

O

17

O 19

O

372

3 Diterpenoids

1082 Juncenolide D Type: Briarane diterpenoids. C31H40O15 White amorphous powder, [α]D24 = −11° (c = 0.10, CHCl3); amorph. solid, [α]D25 = −10.3° (c = 0.2, CH2Cl2). Source: Gorgonian Dichotella gemmacea (South China Sea). Pharm: Cytotoxic (A549, IC50 = (37.1 ± 4.2) μmol/L, control Adriamycin, IC50 = (2.8 ± 0.32)μmol/L; MG63, IC50 > 46.0 μmol/L, Adriamycin, IC50 = (3.2 ± 0.37)μmol/L); antifungal (Agar diffusion assay, 0.05 mg, Microbotryum violaceum, IZR = 6.0 mm, control Penicillin, IZR = 7.0 mm; Septoria tritici,IZR = 7.5 mm, Penicillin, IZR = 6.0 mm); antibacterial (Agar diffusion assay, 0.05 mg, Escherichia coli,IZR = 12.5 mm, control Penicillin, IZR = 15.0 mm; Bacillus megaterium, IZR = 6.0 mm, Penicillin, IZR = 8.0 mm). Ref: Y. -C. Shen, et al, JNP, 2003, 66, 302│P. -J. Sung, et al, Biochemical Systematics and Ecology, 2004, 32, 185 (rev)│C. Li, et al, JNP, 2011, 74, 1658│C. Li, et al, Mar. Drugs, 2011, 9, 1403 O

O O

O

15

O O

O

16

2 14

1

11

10

H

O

20

O

O 9

OH O

O 18

19

17

O

O

1083 Juncenolide J Type: Briarane diterpenoids. C31H43ClO12 Amorph. powder, [α]D = +14° (c = 0.2, CH2Cl2). Source: Gorgonians Dichotella gemmacea (Beibuwan Bay, Guangxi, China) and Junceella juncea. Pharm: Cytotoxic (A549, IC50 > 46.7 μmol/L, control Adriamycin, IC50 = 2.8 μmol/L; MG63, IC50 > 46.7 μmol/L, control Adriamycin, IC50 = 3.2 μmol/L). Ref: S. -S. Wang, et al, Helv. Chim. Acta, 2009, 92, 2092│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)│C. Li, et al, BoMCL,2012, 22, 4368 O

O O

O

2

O

14 12

O

9

O

OH

Cl

H O O

8

O

17

O

3.18 Briarane diterpenoids

373

1084 Juncenolide K Type: Briarane diterpenoids. C26H34O9 Amorph. powder, [α]D = −85° (c = 0.2, CH2Cl2). Source: Gorgonian Junceella juncea (Taiwan waters). Pharm: Anti-inflammatory (weak). Ref: Y. -C. Lin, et al, CPB, 2005, 53, 128│S. S. Wang, et al, Helv. Chim. Acta, 2009, 92, 2092│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O

O

O

15 2

O

14

1

11

10

H 20

9

O

O

O

17

19

18

O

1085 Juncenolide M Frajunolide S Type: Briarane diterpenoids. C28H35ClO12 Colorless amorphous solid, [α]D25 = −42° (c = 0.05, CH2Cl2). Source: Gorgonians Junceella juncea (Taitung County, Taiwan) and Junceella fragilis (Tai-Tong county, Taiwan). Pharm: Antiinflammatory (10 μg/mL, inhibits superoxide anion O2•− generation, hmn neutrophils in response to fMLP/CB, InRt = (7.6 ± 2.8)%), control Genistein, InRt = (65.0 ± 5.7)%); elastase release inhibitor (10 μg/mL, hmn neutrophils in response to fMLP/CB, InRt = (15.9 ± 5.5)%, control Genistein, InRt = (51.6 ± 5.9)%). Ref: J. -Y. Chang, et al, Mar. Drugs, 2012, 10, 1321│C. -C. Liaw, et al, Mar. Drugs, 2013, 11, 2042 O

O O

O O

Cl

H O

OH O O O

O O

1086 Juncenolide N Type: Briarane diterpenoids. C24H34O8 Colorless amorphous solid, [α]D25 = −60° (c = 0.05, CH2Cl2). Source: Gorgonian Junceella juncea (Taitung County, Taiwan). Pharm: Anti-inflammatory (10 μg/mL, inhibits superoxide anion O2•− generation, hmn neutrophils in response to fMLP/CB, InRt = (6.7 ± 2.9)%), control Genistein, InRt = (65.0 ± 5.7)%); elastase release inhibitor (10 μg/mL, hmn neutrophils in

374

3 Diterpenoids

response to fMLP/CB, InRt = (29.0 ± 5.6)%, control Genistein, InRt = (51.6 ± 5.9)%). Ref: J. -Y. Chang, et al, Mar. Drugs, 2012, 10, 1321 O OH

O

H OH O

O O

O

1087 Juncenolide O Juncin Z Type: Briarane diterpenoids. C29H38O13 Colorless amorphous solid, [α]D25 = +4° (c = 0.05, CH2Cl2); powder, [α]D = +31.57° (c = 0.95, CHCl3). Source: Gorgonians Junceella juncea (Taitung County, Taiwan), Junceella juncea and Junceella fragilis (Taiwan waters). Pharm: Anti-inflammatory (10 μg/mL, inhibits superoxide anion O2•− generation, hmn neutrophils in response to fMLP/CB, InRt = (27.6 ± 7.0)%), control Genistein, InRt = (65.0 ± 5.7)%); elastase release inhibitor (10 μg/mL, hmn neutrophils in response to fMLP/CB, InRt = (35.9 ± 7.4)%, control Genistein, InRt = (51.6 ± 5.9)%); antifoulant (US Navy program, larval settlement of barnacle Balanus amphitrite at nontoxic concentrations, EC50 = 1.47 μg/mL; standard requirement EC50 = 25 μg/mL). Ref: S. -H. Qi, et al, Tetrahedron, 2006, 62, 9123│P. -J. Sung, et al, Bull. Chem. Soc. Jpn., 2009, 82, 1426│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)│J. -Y. Chang, et al, Mar. Drugs, 2012, 10, 1321 O

O O

O

O O O O

H OH O O

O O

1088 Junceol A Type: Briarane diterpenoids. C31H44O11 Powder, mp 105–108 °C, [α]D23 = +1.3° (c = 0.3, CHCl3). Source: Gorgonian Junceella juncea (Taiwan waters). Pharm: Anti-

3.18 Briarane diterpenoids

375

inflammatory (significant). Ref: P. -J. Sung, et al, Tetrahedron, 2008, 64, 4224│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)

O

O

O O

O

O 15 2

14

1

11

10 9

OH

H O

O O

O

1089 Junceol B Type: Briarane diterpenoids. C35H49ClO14 Powder, mp 223–226 °C, [α]D23 = −24° (c = 0.02, CHCl3). Source: Gorgonian Junceella juncea (Taiwan waters). Pharm: Anti-inflammatory (significant). Ref: P. -J. Sung, et al, Tetrahedron, 2008, 64, 4224│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)

O O O O

O

O

O 15 2

14

1

11

10 9

O

OH

Cl

H

O

O O

O

O

1090 Junceol C Type: Briarane diterpenoids. C38H55ClO14 Powder, mp 260–262 °C, [α]D23 = +21° (c = 0.02, CHCl3). Source: Gorgonian Junceella juncea (Taiwan waters). Pharm: Anti-inflammatory (significant). Ref: P. -J. Sung, et al, Tetrahedron, 2008, 64, 4224│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)

376

3 Diterpenoids

O O

O

O O

O

O

15 2

14

1

11

10 9

O

OH

Cl

H

O

O

O O

O

1091 Junceol D Type: Briarane diterpenoids. C35H50O13 Powder, mp 105–108 °C, [α]D23 = +29° (c = 0.04, CHCl3). Source: Gorgonian Junceella juncea (Taiwan waters). Pharm: Cytotoxic (CCRF-CEM, IC50 = 1.3 μg/mL, DLD-1, IC50 = 10.0 μg/mL). Ref: P. -J. Sung, et al, CPB, 2008, 56, 1276│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

O

O O

O

O

15 2

14

1

11

10 9

OH

H O O

O

O

1092 Junceol E Type: Briarane diterpenoids. C30H42O11 Powder, mp 111–113 °C, [α]D23 = −6° (c = 0.09, CHCl3). Source: Gorgonian Junceella juncea (Taiwan waters). Pharm: Anti-inflammatory (weak). Ref: P. -J. Sung, et al, CPB, 2008, 56, 1276│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)

3.18 Briarane diterpenoids

377

O

O O

O

O

O

15 2

14

1

11

10 9

OH

H O

O O

O

1093 Junceol F Type: Briarane diterpenoids. C31H44O11 Powder, mp 116–118 °C, [α]D23 = −9° (c = 0.03, CHCl3). Source: Gorgonian Junceella juncea (Taiwan waters). Pharm: Antiinflammatory (moderate); cytotoxic (CCRF-CEM, IC50 = 4.9 μg/mL). Ref: P. -J. Sung, et al, CPB, 2008, 56, 1276│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

O

O O

15 2

14

1

11

10

H

9

O O

OH O

O

1094 Junceol G Type: Briarane diterpenoids. C31H44O11 Powder, mp 240–243 °C, [α]D23 = −21° (c = 0.02, CHCl3). Source: Gorgonian Junceella juncea (Taiwan waters). Pharm: Anti-inflammatory (weak); cytotoxic (CCRF-CEM, IC50 = 4.4 μg/mL). Ref: P. -J. Sung, et al, CPB, 2008, 56, 1276│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)

378

3 Diterpenoids

O O

O

O

15

O

2

O

14

1

11

10

OH

9

H O

O O

O

1095 Junceol H Type: Briarane diterpenoids. C30H42O11 Powder, mp 272–275 °C, [α]D23 = −33° (c = 0.03, CHCl3). Source: Gorgonian Junceella juncea (Taiwan waters). Pharm: Anti-inflammatory (weak); cytotoxic (CCRF-CEM, IC50 = 7.2 μg/mL, DLD-1, IC50 = 17.0 μg/mL). Ref: P. -J. Sung, et al, CPB, 2008, 56, 1276│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O O

O

O

15

O

2

O

14

1

11

10 9

OH

H O

O O

O

1096 Juncin E Type: Briarane diterpenoids. C30H37ClO14 Oil, [α]D25 = −66° (c = 0.02, CHCl3). Source: Gorgonian Junceella juncea. Pharm: Insecticide. Ref: S. Isaacs, et al, JNP, 1990, 53, 596│P. -J. Sung, et al, Biochemical Systematics and Ecology, 2004, 32, 185 (rev) O

O O

O

O

O

15

O

O

16

2

O

14

1

11

10

H 20

9

Cl O

O 18

O

OH

17

19

O

3.18 Briarane diterpenoids

379

1097 Juncin O Type: Briarane diterpenoids. C33H43ClO14 White amorphous powder (MeOH), [α]D24 = +30° (c = 0.12, CHCl3), [α]D = +36° (c = 1.0, CHCl3). Source: Gorgonians Dichotella gemmacea (South China Sea) and Junceella juncea. Pharm: Antifeedant (lepidopteran insect cutworm Spodoptera litura (second-instar larvae), 500 μg/mL, 90.7%); cytotoxic (second-instar larvae of lepidopteran insect cutworm Spodoptera litura, 100 μg/mL, mortality: 8.7% in 24h and 11.9% in 48h, medium). Ref: S. -H. Qi, et al, JNP, 2004, 67, 1907│S. -H. Qi, et al, Chem. Nat. Comp., 2009, 45, 49│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)│C. Li, et al, JNP, 2011, 74, 1658 O

O O

O

15

O O

16

2

O

14

1

11

10

H

O

20

O

9

OH

Cl O

O

17 19

O

18

O

1098 Juncin P Type: Briarane diterpenoids. C28H35ClO13 Powder, [α]D = −6.8° (c = 0.24, CHCl3). Source: Gorgonian Junceella juncea (South China Sea). Pharm: Antifeedant (lepidopteran insect cutworm Spodoptera litura (second-instar larvae), 500 μg/mL, 69.0%); cytotoxic (second-instar larvae of lepidopteran insect cutworm Spodoptera litura, 100 μg/mL, mortality: 25.3% in 24h and 29.7% in 48h, medium). Ref: S. -H. Qi, et al, JNP, 2004, 67, 1907│S. -H. Qi, et al, Chem. Nat. Comp., 2009, 45, 49│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O

O

O O

OH

14

O O

Cl O

H O O

O O

1099 Juncin Q Type: Briarane diterpenoids. C26H34O13 Powder, [α]D = −14° (c = 0.4, Py). Source: Gorgonian Junceella juncea (South China Sea). Pharm: Antifeedant (lepidopteran

380

3 Diterpenoids

insect cutworm Spodoptera litura (second-instar larvae), 500 μg/mL, 46.5%); cytotoxic (second-instar larvae of lepidopteran insect cutworm Spodoptera litura, 100 μg/mL, mortality: 31.3% in 24h and 44.0% in 48h, medium). Ref: S. -H. Qi, et al, JNP, 2004, 67, 1907│S. -H. Qi, et al, Chem. Nat. Comp., 2009, 45, 49│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O OH 15

O

O O

16

2 14

1

11

10

HO

H

O

20

OH OH

9

O

O

O 17

19

18

O

1100 Juncin R Type: Briarane diterpenoids. C31H43ClO14 White amorphous powder, [α]D24 = −37° (c = 1.14, CHCl3). Source: Gorgonians Dichotella gemmacea (South China Sea) and Junceella juncea. Pharm: Cytotoxic (A549, IC50 = (13.9 ± 2.5)μmol/L, control Adriamycin, IC50 = (2.8 ± 0.32)μmol/L; MG63, IC50 = (5.6 ± 1.2)μmol/L, Adriamycin, IC50 = (3.2 ± 0.37)μmol/L); antifungal (Agar diffusion assay, 0.05 mg, Microbotryum violaceum, IZR = 7.5 mm, control Penicillin, IZR = 7.0 mm; Septoria tritici,IZR = 7.5 mm, Penicillin, IZR = 6.0 mm); antibacterial (Agar diffusion assay, 0.05 mg, Escherichia coli,IZR = 14.0 mm, control Penicillin, IZR = 15.0 mm; Bacillus megaterium, IZR = 6.0 mm, Penicillin, IZR = 8.0 mm); antifoulant (US Navy program, larval settlement of barnacle Balanus amphitrite at nontoxic concentrations, EC50 = 0.004 μg/mL; standard requirement EC50 = 25 μg/mL). Ref: S. -H. Qi, et al, Tetrahedron, 2006, 62, 9123│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)│C. Li, et al, Mar. Drugs, 2011, 9, 1403│C. Li, et al, JNP, 2011, 74, 1658 O

O O O

O

O O

2

Cl

12

O

9

O

OH

H O O

O O

1101 Juncin S Type: Briarane diterpenoids. C31H43ClO14 White amorphous powder, [α]D24 = −33° (c = 0.97, CHCl3). Source: Gorgonians Dichotella gemmacea (South China Sea) and

3.18 Briarane diterpenoids

381

Junceella juncea. Pharm: Cytotoxic (A549, IC50 = (20.2 ± 2.3)μmol/L, control Adriamycin, IC50 = (2.8 ± 0.32)μmol/L; MG63, IC50 = (16.5 ± 2.4)μmol/L, Adriamycin, IC50 = (3.2 ± 0.37)μmol/L); antifungal (Agar diffusion assay, 0.05 mg, Microbotryum violaceum, IZR = 5.5 mm, control Penicillin, IZR = 7.0 mm; Septoria tritici,IZR = 7.0 mm, Penicillin, IZR = 6.0 mm); antibacterial (Agar diffusion assay, 0.05 mg, Escherichia coli,IZR = 10.0 mm, control Penicillin, IZR = 15.0 mm; Bacillus megaterium, IZR = 0 mm, Penicillin, IZR = 8.0 mm); antifoulant (US Navy program, larval settlement of barnacle Balanus amphitrite at nontoxic concentrations, EC50 = 0.34 μg/mL; standard requirement EC50 = 25 μg/mL). Ref: S. -H. Qi, et al, Tetrahedron, 2006, 62, 9123│C. Li, et al, JNP, 2011, 74, 1658│C. Li, et al, Mar. Drugs, 2011, 9, 1403│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O O

O

O O

2

Cl

12

O

9

O

OH

H O

O O

O

1102 Juncin T Type: Briarane diterpenoids. C36H48O17 Powder, [α]D = −14° (c = 0.4, CHCl3). Source: Gorgonian Junceella juncea (South China Sea). Pharm: Antifoulant (US Navy program, larval settlement of barnacle Balanus amphitrite at nontoxic concentrations, EC50 = 2.65 μg/mL; standard requirement EC50 = 25 μg/mL). Ref: S. -H. Qi, et al, Tetrahedron, 2006, 62, 9123│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2 773 (rev) O

O

O

O O

2

14 12

O

O

O

O

16 9

O

OH

OH

H O

O O

8

O O

1103 Juncin U Type: Briarane diterpenoids. C34H46O14 White amorphous powder, [α]D24 = −20° (c = 0.87, CHCl3). Source: Gorgonians Dichotella gemmacea (South China Sea) and Junceella juncea. Pharm: Cytotoxic (A549, IC50 > 43.2 μmol/L, control Adriamycin, IC50 = (2.8 ± 0.32)μmol/L; MG63, IC50 = > 43.2 μmol/L, Adriamycin, IC50 = (3.2 ± 0.37)

382

3 Diterpenoids

μmol/L); antifungal (Agar diffusion assay, 0.05 mg, Microbotryum violaceum, IZR = 0 mm, control Penicillin, IZR = 7.0 mm; Septoria tritici,IZR = 7.5 mm, Penicillin, IZR = 6.0 mm); antibacterial (Agar diffusion assay, 0.05 mg, Escherichia coli,IZR = 11.0 mm, control Penicillin, IZR = 15.0 mm; Bacillus megaterium,IZR = 8.0 mm, Penicillin, IZR = 8.0 mm); antifoulant (US Navy program, larval settlement of barnacle Balanus amphitrite at nontoxic concentrations, EC50 = 1.61 μg/mL; standard requirement EC50 = 25 μg/mL). Ref: S. -H. Qi, et al, Tetrahedron, 2006, 62, 9123│C. Li, et al, JNP, 2011, 74, 1658│C. Li, et al, Mar. Drugs, 2011, 9, 1403│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O O

O

O

16

O

2

O

13

O

9

O

OH

H 8

O O

O O

1104 Juncin V Type: Briarane diterpenoids. C27H36O13 Powder, [α]D = −13.1° (c = 0.32, CHCl3). Source: Gorgonian Junceella juncea (South China Sea). Pharm: Antifoulant (US Navy program, larval settlement of barnacle Balanus amphitrite at nontoxic concentrations, EC50 = 3.77 μg/mL; standard requirement EC50 = 25 μg/mL). Ref: S. -H. Qi, et al, Tetrahedron, 2006, 62, 9123│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O O

O

OH

16

O

2

O

13

HO

9

O

OH

H O O

8

O O

1105 Juncin W Type: Briarane diterpenoids. C28H36O14 Powder, [α]D = −11.7° (c = 1.45, CHCl3). Source: Gorgonian Junceella juncea (South China Sea). Pharm: Antifoulant (US Navy program, larval settlement of barnacle Balanus amphitrite at nontoxic

3.18 Briarane diterpenoids

383

concentrations, EC50 = 21.06 μg/mL; standard requirement EC50 = 25 μg/mL). Ref: S. -H. Qi, et al, Tetrahedron, 2006, 62, 9123│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O O

OH O O HO

2

14 12

9

O

O OH

O

H 8

O O

O O

1106 Juncin X Type: Briarane diterpenoids. C30H40O14 Powder, [α]D = +21.34° (c = 0.89, CHCl3). Source: Gorgonian Junceella juncea. Pharm: Antifoulant (US Navy program, larval settlement of barnacle Balanus amphitrite at nontoxic concentrations, EC50 = 0.004 μg/mL; standard requirement EC50 = 25 μg/mL). Ref: S. -H. Qi, et al, Tetrahedron, 2006, 62, 9123│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O

O

O

O

O O

2

O

12

O

9

OH

O

17

H

O

O O

1107 Juncin Y Type: Briarane diterpenoids. C30H40O13 Powder, [α]D = +36° (c = 1, CHCl3). Source: Gorgonians Junceella juncea (South China Sea), Junceella fragilis (Taiwan waters). Pharm: Antifoulant (US Navy program, larval settlement of barnacle Balanus amphitrite at nontoxic concentrations, EC50 = 0.14 μg/mL; standard requirement EC50 = 25 μg/mL). Ref: S. -H. Qi, et al, Tetrahedron, 2006, 62, 9123│P. -J. Sung, et al, Bull. Chem. Soc. Jpn., 2009, 82, 1426│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)

384

3 Diterpenoids

O

O

O

O

O

O

15 1

11

10

H 20

O

16

2 14

O OH

9

O

O

17

O

19

18

O

1108 Juncin Z2 Type: Briarane diterpenoids. C34H47ClO14 Source: Gorgonian Junceella juncea (South China Sea). Pharm: Antifeedant (lepidopteran insect cutworm Spodoptera litura (second-instar larvae), 500 μg/mL, 84.5%, medium); cytotoxic (second-instar larvae of lepidopteran insect cutworm Spodoptera litura, 100 μg/mL, cell mortality: 20.5% in 24h and 43.2% in 48h); antifoulant (larvae of barnacle Balanus amphitrite, EC50 = 0.004 μg/mL). Ref: S. -H. Qi, et al, Chem. Nat. Comp., 2009, 45, 49│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev) O

O O

O

15

O O

2

O O O

14

1

11

10

H 20

16 9

O

OH

Cl O

17 19

O

18

O

1109 Juncin ZI Type: Briarane diterpenoids. C26H33ClO11 Powder, [α]D = +9.3° (c = 1.29, CHCl3). Source: Gorgonians Junceella juncea (South China Sea), Junceella fragilis (Taiwan waters). Pharm: Antifoulant (US Navy program, larval settlement of barnacle Balanus amphitrite at nontoxic concentrations, EC50 = 0.51 μg/mL; standard requirement EC50 = 25 μg/mL). Ref: S. -H. Qi, et al, Tetrahedron, 2006, 62, 9123│P. -J. Sung, et al, Bull. Chem. Soc. Jpn., 2009, 82, 1426│Y. -C. Wu, et al, Mar. Drugs, 2011, 9, 2773 (rev)

3.18 Briarane diterpenoids

385

O

O

O

O

OH

O

11

Cl O

H O

O O

O

1110 Juncin ZII Type: Briarane diterpenoids. C32H45ClO13 Source: Gorgonian Junceella juncea (Sanya, Hainan, China). Pharm: Antifoulant (barnacle Balanus Amphitrite, potent). Ref: S. H. Qi, et al, Chem. Nat. Compd., 2009, 45, 49 O O

OH O O

O

OH O

H

O

O

O

Cl

O

O

1111 Malayenolide A Type: Briarane diterpenoids. C29H34O6 Amorph. solid, [α]D = +158.1° (c = 1.05, CHCl3). Source: Sea pen Veretillum malayense (Indonesia). Pharm: Toxic (brine shrimp, LC50 = 100 μg/mL). Ref: X. Fu, et al, JNP, 1999, 62, 584 O O O O

11

H O O

386

3 Diterpenoids

1112 Malayenolide B Type: Briarane diterpenoids. C29H34O7 Amorph. solid, [α]D = +85.0° (c = 0.6, CHCl3). Source: Sea pen Veretillum malayense (Indonesia). Pharm: Toxic (brine shrimp, LC50 < 2μg/mL). Ref: X. Fu, et al, JNP, 1999, 62, 584 O O O O

11

O

H O O

1113 Malayenolide C Type: Briarane diterpenoids. C27H36O6 Amorph. solid, [α]D = +69.9° (c = 1.53, CHCl3). Source: Sea pen Veretillum malayense (Indonesia). Pharm: Toxic (brine shrimp, LC50 = 20 μg/mL). Ref: X. Fu, et al, JNP, 1999, 62, 584 O

O O

O

11

H O O

1114 Malayenolide D Type: Briarane diterpenoids. C27H36O7 Amorph. solid, [α]D = +29.0° (c = 0.69, CHCl3). Source: Sea pen Veretillum malayense (Indonesia). Pharm: Toxic (brine shrimp, LC50 = 20 μg/mL). Ref: X. Fu, et al, JNP, 1999, 62, 584

3.18 Briarane diterpenoids

387

O

O O

O

11

O

H O O

1115 Minabein 8 Renillafoulin A Type: Briarane diterpenoids. C24H32O9 Cryst. (MeOH) or white solid, Soluble in MeOH, CHCl3; poorly soluble in H2O. Source: Soft corals Minabea sp. and Eleutherobia sp., sea pen Renilla reniformis. Pharm: Antifoulant (inhibits barnacle larval settlement, EC50 = 0.02–0.2 pg/mL). Ref: P. A. Kiefer, et al, JOC, 1986, 51, 4450│M. B. Ksebati, et al, Bull. Soc. Chim. Belg., 1986, 95, 835│S. C. Lievens, et al, JNP, 2004, 67, 2130 O O 2 12 9

O HO

OH

H O

O O

O

1116 Nuiinoalide A Type: Briarane diterpenoids. C28H37ClO12 Solid, [α]D = −15° (c = 1.2, CHCl3). Source: An unidentified octocoral. Pharm: Immunomodulatory. Ref: M. T. Hamann, et al, Heterocycles, 1996, 42, 325 O

O

O

O O O

OH O

H O O

Cl O O

388

3 Diterpenoids

1117 Praelolide Type: Briarane diterpenoids. C28H35ClO12 Source: Gorgonians Dichotella gemmacea (Beibuwan Bay, Guangxi, China), Gorgonella umbraculum, Junceella fragilis, Plexauroides praelonga and Menella praelonga. Pharm: Cytotoxic (A549, IC50 > 50.1 μmol/L, control Adriamycin, IC50 = 2.8 μmol/L; MG63, IC50 > 50.1 μmol/L, control Adriamycin, IC50 = 3.2 μmol/L). Ref: Y. Luo, et al, Bull. Chem. Soc. Jpn., 1983, 83│J. Dai, et al, Sci. Sin., Ser. B: (Engl. edn.), 1985, 28, 1132│J. Shin, et al, Tetrahedron, 1989, 45, 1633│C. Li, et al, BoMCL,2012, 22, 4368 O

O

O

O O

O

O Cl O

H O

O O

O

1118 12-Ptilosarcenol (2β,3Z,6α,7α,9β,12α)-6-Chloro-2,9-diacetoxy-8,12-dihydroxy-3,5(16),13-briaratrien-18,7olide Type: Briarane diterpenoids. C24H31ClO8 [α]D26 = −62.9° (c = 0.56, CH2Cl2). Source: Sea pen Ptilosarcus gurneyi. Pharm: Insecticide. Ref: R. L. Hendrickson, et al, Tetrahedron, 1986, 42, 6565 O O 2

HO

14

1

11

10 9

OH

Cl

H O O

O O

1119 Ptilosarcenone Type: Briarane diterpenoids. C24H29ClO8 Cryst., mp 153–155 °C, [α]D26 = −72.4° (c = 1.01, CH2Cl2). Source: Sea pen Ptilosarcus gurneyi (Northern Pacific Ocean). Pharm: Insecticide. Ref: S. J. Wratten, et al, Tet. Lett., 1977, 1559│R. L. Hendrickson, et al, Tetrahedron, 1986, 42, 6565

3.18 Briarane diterpenoids

389

O O

OH

O

Cl

H O

O O

O

1120 Ptilosarcone Type: Briarane diterpenoids. C28H37ClO10 Ptilosarcone decomposed in polar solvents to produce ptilosarcenone. Source: Sea pen Ptilosarcus gurneyi (Northern Pacific Ocean). Pharm: Toxic. Ref: S. J. Wratten, et al, Tet. Lett., 1977, 1559 O

O O

O

OH

O

Cl

H O

O O

O

1121 Renillafoulin B Type: Briarane diterpenoids. C25H34O9 Soluble in MeOH, CHCl3; poorly soluble in H2O. Source: Sea pen Renilla reniformis. Pharm: Antifoulant (inhibits barnacle larval settlement, EC50 = 0.02–0.2 pg/mL). Ref: P. A. Kiefer, et al, JOC, 1986, 51, 4450 O O 2 12 9

O HO

OH

H O O

O O

1122 Renillafoulin C Type: Briarane diterpenoids. C26H36O9 Soluble in MeOH, CHCl3; poorly soluble in H2O. Source: Sea pen Renilla reniformis. Pharm: Antifoulant (inhibits barnacle

390

3 Diterpenoids

larval settlement, EC50 = 0.02–0.2 pg/mL). Ref: P. A. Kiefer, et al, JOC, 1986, 51, 4450 O O 2 12 9

O

OH

H

HO

O

O O

O

1123 Solenolide A Type: Briarane diterpenoids. C28H41ClO9 Cryst. (Et2O), mp 132–133 °C, [α]D20 = −56° (c = 0.63, CHCl3). Source: Gorgonian Solenopodium sp., gorgonian Briareum violacea (depth of 15 m, Pingtung county, Taiwan, in May 2007). Pharm: Antiviral; anti-inflammatory. Ref: A. Groweiss, et al, JOC, 1988, 53, 2401│C. -C. Liaw, et al, Mar. Drugs, 2014, 12, 4677. O O O O O

OH

Cl

H OH

O O

1124 Stecholide A Type: Briarane diterpenoids. C28H38O11 White solid (Me2CO/hexane), mp 113–115 °C, [α]D = +54.8° (c = 0.23, CHCl3). Source: Gorgonian Solenopodium stechei (Great Barrier Reef). Pharm: Cytotoxic (P388, ED50 = 4.5 μg/mL). Ref: S. J. Bloor, et al, JOC, 1992, 57, 1205

3.18 Briarane diterpenoids

O

O

O O

O

391

O

O

OH

O O

H

O

1125 Stecholide B Type: Briarane diterpenoids. C27H36O11 Crystals (C6H6/hexane), mp 123–127 °C, [α]D = +89.0° (c = 0.09, CHCl3). Source: Gorgonian Solenopodium stechei (Great Barrier Reef). Pharm: Cytotoxic (P388, ED50 = 5.4 μg/mL). Ref: S. J. Bloor, et al, JOC, 1992, 57, 1205 O

O

O O

O

O

O

OH

O O

H

O

1126 Stecholide H Type: Briarane diterpenoids. C26H36O9 White powder, mp 84–88 °C, [α]D = −57.2° (c = 0.32, CHCl3). Source: Gorgonian Solenopodium stechei (Great Barrier Reef). Pharm: Cytotoxic (P388, ED50 = 10 μg/mL). Ref: S. J. Bloor, et al, JOC, 1992, 57, 1205 O

O O

O

HO

H OH

O O O

392

3 Diterpenoids

1127 Stylatulide Type: Briarane diterpenoids. C26H35ClO10 Cryst. (CH2Cl2/hexane), mp 179–181 °C, [α]D = +65 °C. Source: Sea pen Stylatula sp. Pharm: Toxic (to copepod larvae). Ref: S. J. Wratten, et al, JACS, 1977, 99, 2824│S. J. Wratten, et al, Tetrahedron, 1979, 35, 1907 O

O O

O

OH O

Cl

H O

O O

O

1128 Tubiporein Briarlide G Type: Briarane diterpenoids. C28H36O12 Needles (MeOH), mp 71–71.5 °C, [α]D27.5 = −36.6° (c = 1.0, CHCl3), [α]D = −73° (c = 0.2, MeOH). Source: Soft coral Tubipora sp., gorgonian Briareum sp. Pharm: Cytotoxic. Ref: T. Natori, et al, Tet. Lett., 1990, 31, 689│T. Iwagawa, et al, JNP, 2003, 66, 1412 O

O O O O 12

O

HO

H O O O

O O

1129 Violide A Type: Briarane diterpenoids. C32H46O12 Cryst. (EtOH), mp 183.8–184.1 °C, [α]D = +33° (c = 0.1, MeOH). Source: Soft coral Pachyclavularia violacea, gorgonian Briareum sp. Pharm: Ichthyotoxic. Ref: T. wagawa, et al, Heterocycles, 1998, 48, 123; 1999, 51, 1653

3.18 Briarane diterpenoids

393

O

O

OH

O

O

2

9

HO HO

H OO

O

O

O

1130 Violide B Type: Briarane diterpenoids. C28H36O13 Amorph. solid, [α]D = +50.7° (c = 0.07, CHCl3). Source: Soft coral Pachyclavularia violacea, gorgonian Briareum sp. Pharm: Ichthyotoxic. Ref: T. wagawa, et al, Heterocycles, 1998, 48, 123; 1999, 51, 1653 O

O

O O

O

O

2

HO

9

HO

H

O O

O

O O

1131 Violide N 8,17-Epoxy-4-octanoyloxy-2,9-diacetoxy-11,12,16-trihydroxy-5,13-briaradien-18,7-olide Type: Briarane diterpenoids. C32H46O12 Amorph., [α]D = –2.3° (c = 0.1, MeOH). Source: Gorgonian Briareum sp. (Japan waters). Pharm: Cytotoxic. Ref: T. Iwagawa, et al, Heterocycles, 1998, 48, 123; 2000, 53, 1789 O

O O

O

OH

13 11

HO

HO

H OO O

O

O

Index 1 Compound Name and Synonym Index This index lists in alphabetical order all active compound’s 1,278 entry names including both 1,131 key names and 147 synonym names contained in the bodies of compound entries. A equal sign ( = ) and compound code number (from 1 to 1,131) follow the name immediately for locating the compound in the “Handbook of Active Marine Natural Products Volume 1” book. Following symbols are ineffective in ordering: D-, L-, dl, R-, S-, E-, Z-, O-, N-, C-, H-, cis-, trans-, ent-, epi-, meso-, erythro-, threo-, sec-, seco-§, m-, o-, p-, n-, α-, β-, γ-, δ-, ε-, κ-, ξ-, ψ-, ω-, (+), (−), (±) etc., and: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, {, }, [,], (,), ,, ;, , *, ‘, ‘‘, ‘‘‘, →, etc. (§note: In the books regular “seco-” is effective in ordering as “nor-”.) A Abscisic acid = 76. Abscisin II = 76. (3Z,5E)-1-Acetoxy-8-bromo-4,7-dichloro-3,7dimethylocta-3,5-diene = 5. 2-Acetoxy-15-bromo-7,16-dihydroxy-3palmitoylneoparguera-4(19),9(11)- diene = 481. 8β-Acetoxycapnell-9(12)-ene-10α-ol = 310. 3β-Acetoxycapnellene-8β,10α,14-triol = 311. (1R,3Z,7E,11E,14S)-18-Acetoxy-3,7,11,15(17)cembratetraen-16,14-olide = 543. (7E)-1-Acetoxy-8-chloro-7-(dichloromethyl)3-methyloct-7-en-4-one = 6. (7Z)-1-Acetoxy-8-chloro-7-(dichloromethyl)3-methyloct-7-en-4-one = 7. 11-Acetoxy-4-deoxyasbestinin B = 942. 11-Acetoxy-4-deoxyasbestinin D = 943. 3-Acetoxy-9,7(11)-dien-7α-hydroxy-8oxoeremophilane = 162. 9-Acetoxy-5,8:12,13-diepoxycembr-15(17)— en-16,4-olide = 544. (3E)-6-Acetoxy-3,11-dimethyl-7methylidendodeca-1,3,10-triene = 51. 11-Acetoxy-8-drimen-12,11-olide = 196. 3-Acetoxy-E-γ-bisabolene = 85. 18-Acetoxy-3R,4S-epoxy-13R-Hydroxy-7,11,15 (17)-cembratrien-16,14-olide = 545. 18-Acetoxy-3R,4S-epoxy-13S-Hydroxy-7,11,15 (17)-cembratrien-16,14-olide = 546. 16-Acetoxy-isoparguerol = 489. 6-Acetoxy-litophynin E = 800. 6β-Acetoxyolepupuane = 197. 12-Acetoxypseudopterolide = 786. 13-Acetoxysarcocrassolide = 547. 13-Acetoxysarcophytoxide = 548. 19-Acetoxy-13(16),14-Spongiadiene = 493. 11α-Acetoxy-13-spongien-16-one = 494.

https://doi.org/10.1515/9783110655131-004

11β-Acetoxy-13-spongien-16-one = 495. 12-Acetoxytetrahydrosulphurin I = 517. 3-Acetylcladiellisin = 801. Acetylehrenberoxide B = 549. Acetylisoobtusol = 268. 14-Acetylthioxyfurodysinin lactone = 250. 4-O-Acetylverrol = 134. (2α,3β,6α)-2-Africananol = 309. 3(15)-Africanene = 308. 9(15)-Africanene = 308. Africanol = 309. Agallochaol K = 537. Agallochaol O = 538. Agallochaol P = 539. Agallochaol Q = 540. Agelasidine B = 371. (+)-Agelasidine C = 372. Agelasidine E = 373. Agelasidine F = 374. Agelasine A = 420. Agelasine B = 421. Agelasine C = 408. 5,9-diepi-Agelasine C = 409. Agelasine D = 422. Agelasine E = 375. Agelasine F = 376. Agelasine G = 423. Agelasine H = 424. Agelasine I = 425. Agelasine J = 410. Agelasine K = 426. Agelasine L = 427. Agelasine O = 411. Agelasine P = 428. Agelasine Q = 429. Agelasine R = 430. Agelasine S = 412.

396

Index 1 Compound Name and Synonym Index

Agelasine T = 431. Agelasine U = 432. Ageline A = 376. Ageline B = 433. (+)-Agelisamine A = 413. (+)-Agelisamine B = 414. Aignopsanoic acid = 289. Aignopsanoic acid methyl ester = 290. Ainigmaptilone A = 141. Albican-11,14-diol = 198. (+)-Albicanol = 199. (+)-Albicanol acetate = 200. Alcyonin = 802. Alcyopterosin A = 246. Alcyopterosin C = 247. Alcyopterosin E = 248. Alcyopterosin H = 249. (+)-Alloaromadendrene = 238. Alloisoobtusol = 257. Ambliofuran = 351. Ambliol A = 377. Ambliol B = 415. Ambliol C = 416. Ambliolide = 378. Americanolide D = 232. Anthogorgiene G = 222. (–)-Anthoplalone = 121. Anthoptilide A = 955. Anthoptilide B = 956. Anthoptilide C = 957. Anthoptilide D = 958. Anthoptilide E = 959. Antibiotic JBIR 28 = 163. Antibiotic RES-1149-2 = 201. Anverene = 8. Aplysiapyranoid A = 9. Aplysiapyranoid B = 10. Aplysiapyranoid C = 11. Aplysiapyranoid D = 12. Aplysiaterpenoid A = 36. 12-epi-Aplysillin = 496. Aplysistatin = 77. Aplysulphuride = 518. Arenaran A = 78. (1α,4β,5β,6α,7α)-10(14)-Aromadendren-4-ol = 243. Asbestinin 6 = 944. Asbestinin 7 = 945.

Asbestinin 8 = 946. Asbestinin 9 = 947. Asbestinin 10 = 948. seco-Asbestinin = 949. Asmarine A = 434. Asmarine B = 435. Asperdiol = 550. Aspergiterpenoid A = 86. Astrogorgin = 803. Astrogorgin B = 804. Astrogorgin C = 805. Astrogorgin D = 806. Astrogorgin N = 807. Atractylon = 153. Australin E = 808. Austrodorin = 417. B 12-O-Benzoyl-12-O-deacetylpteroidine = 960. 12-Benzoyl-2,9,14-triacetoxy-6-chloro-4, 8-epoxy-4,12-dihydroxy-5(16)- briaren18,7-olide = 960. Benzyl briaviolide A = 961. (–)-Bifurcadiol = 352. Bifurcane = 353. Bifurcanol = 354. Bipinnapterolide B = 787. Bipinnatin A = 551. Bipinnatin B = 552. Bipinnatin D = 553. 14(4→5),15(10→9)-Bisabeo-3-drimene11-carboxylic acid = 220. (R)-1,3,5,10-Bisabolatetraen-1-ol = 94. Bis(deacyl)solenolide D = 962. Bis(pseudopterane)amine = 788. Brasudol = 142. Briacavatolide C = 963. Briacavatolide D = 964. Briacavatolide E = 965. Briacavatolide F = 966. Briaexcavatin C = 967. Briaexcavatin E = 968. Briaexcavatolide B = 969. Briaexcavatolide F = 970. Briaexcavatolide L = 971. Briaexcavatolide P = 972. Brialalepolide A = 973.

Index 1 Compound Name and Synonym Index

Brialalepolide B = 974. Brialalepolide C = 975. Brianolide = 976. Brianthein A = 977. Brianthein B = 978. Brianthein C = 979. Brianthein X = 980. Brianthein Y = 981. Briarellin A = 809. Briarellin D = 810. Briarellin D hydroperoxide = 811. Briarellin E = 812. Briarellin J = 813. Briarellin K = 814. Briarellin K hydroperoxide = 815. Briarellin L = 816. Briarellin M = 817. Briarellin N = 818. Briarellin O = 819. seco-Briarellinone = 820. Briarellin P = 821. Briarellin S = 822. Briarenolide F = 982. Briarenolide G = 983. Briareolate ester D = 984. Briareolate ester G = 985. Briareolate ester I = 986. Briareolate ester K = 987. Briareolate ester L = 988. Briareolate ester M = 989. Briareolate ester N = 990. Briareolide A = 991. Briareolide B = 992. Briareolide C = 993. Briareolide D = 994. Briareolide E = 995. Briareolide K = 996. Briarlide G = 1128. Briaviolide A = 997. Briaviolide B = 998. Briaviolide C = 999. Briaviolide D = 1000. Briaviolide E = 1001. Briaviolide F = 1002. Briaviolide G = 1003. Briaviolide H = 1004. Briaviolide I = 1005. Briaviolide J = 1006. Briviolide J = 977.

397

4-Bromo-5-bromomethyl-1-(2-chloroethenyl)2,5-dichloro-1-methylcyclo- hexane = 37. 6-Bromo-3-(bromomethyl)-2,3-dichloro7-methyl-1,6-octadiene = 13. 6-Bromo-3-bromomethyl-3,7-dichloro-7-methyl1-octene = 14. 7-Bromo-3-bromomethyl-2,3,6-trichloro7-methyl-1-octene = 25. 10-Bromo-2,7(14)-chamigradiene = 252. 10-Bromo-1,7(14)-chamigradiene-3,9-diol = 253. 10S-Bromo-1,7(14)-chamigradiene-3,9-diol = 269. 10-Bromo-2,7-chamigradien-9-ol = 254. 10-Bromo-2-chloro-2,7(14)-chamigradien-9-ol = 266. 4-Bromo-2-chloro-1-(2-chloroethenyl)-1-methyl5-methylenecyclohexane = 41. 3,4-erythro-1-Bromo-7-dichloromethyl-3methyl-3,4,8-trichloro-1(E),5(E),7(E)octatriene = 15. (1β,7β)-1-Bromo-4(15)-eudesmen-11-ol = 142. 2-Bromo-11-eudesmen-5-ol = 143. 3-Bromo-11-eudesmen-5-ol = 144. (1β,7α)-1-Bromo-4(15)-eudesmen-11-ol = 145. 10-Bromo-7α,8α-epoxychamigr-1-en-3-ol = 255. 4-Bromohamigeran K = 341. (6R,9R,10S)-10-Bromo-9-hydroxy-chamigra2,7(14)-diene = 256. 3-Bromomethyl-3-chloro-7-methyl-1,6octadiene = 16. 3-(Bromomethyl)-2,3-dichloro-7-methyl1,6-octadiene = 17. Z-3-Bromomethylene-2-chloro-7-methyl1,6-octadiene = 18. 3-(Bromomethyl)-2,3,6-trichloro-7-methyl1,6-octadiene = 19. 4-Bromo-2-methyl-5-(1,2,2-trimethyl-3cyclopenten-1-yl)phenol = 124. Bromosphaerol = 952. Bromosphaerone = 953. (1E,3R,4S,5E)-8-Bromo-1,3,4,7-tetrachloro-7chloromethyl-3-methyl-1,5-octadiene = 20. 8-Bromo-1,3,4,7-tetrachloro-3,7-dimethyl-1,5octadiene = 21. 4-Bromo-1,6,8-trichloro-2-ochtodene = 27. (1R*,2R*,3R*,6S*,7S*,9R*,10R*,14R*)-3Butanoyloxycladiell-11(17)-en-6,7diol = 905.

398

Index 1 Compound Name and Synonym Index

C (–)-Cacofuran A = 389. Cacofuran B = 390. Cacospongionolide C = 355. 4,9-Cadinadien-14-oic acid = 193. Caespitane = 87. Caespitol = 88. Calicophirin A = 823. Calicophirin B = 824. Calyculaglycoside A = 554. Calyculaglycoside B = 555. Calyculaglycoside C = 556. Calyculone A = 771. Calyculone B = 772. Calyculone C = 773. Calyculone H = 774. Capillolide = 557. Capilloquinol = 67. 9(12)-Capnellene = 312. Capnell-9(12)-ene-8β,10α-diol = 313. 9(12)-Capnellen-8β-ol = 314. Cartilagineal = 22. Cartilagineol = 257. Caucanolide A = 789. Caucanolide B = 790. Caucanolide C = 791. Caucanolide D = 775. Caucanolide E = 776. Caucanolide F = 777. Caulerpenyne = 52. Caulerpenynol = 53. Cembranoid JNP98-237 = 558. Cembranolide C = 588. (all-E)-3,7,11,15-Cembratetraene = 560. (1Z,3E,7E,11E,14S)-1,3,7,11-Cembratetraen-14-ol = 717. (1S,2S,3E,7E,11E)-3,7,11,15-Cembratetraen-17, 2-olide = 559. (1R,3E,7E,11E)-3,7,11-Cembratrien-15-ol = 679. (1R,3E,7E,11E)-3,7,11-Cembratrien-1-ol = 720. Cembrene A = 560. Cerbinal = 47. Cespitol = 88. Chabranol = 122. Chamigrane epoxide = 258. Chelonaplysin C = 519. Chloroacetoxyhydroxyeremophiltrienone = 164.

4-Chloro-5-(2-chloroethenyl)-1-chloromethyl-5methylcyclohexene = 38. Chlorodesmin = 356. (2β,3Z,6α,7α,9β,12α)-6-Chloro-2,9-diacetoxy8,12-dihydroxy-3,5(16),13-briaratrien-18,7olide = 1118. (1S,2S,3Z,6S,7R,8R,9S,10S,11R, 12R,13S,14R,17R)-6-Chloro-13,14-epoxy2,9-diacetoxy-8,12-dihydroxybriaran-3(4), 5(16)-dien-18,7-olide = 997. 6-Chloro-4,8-epoxy-9-hydroxy-2,14-diacetoxy-5 (16),11-briaradien-18,7-olide = 1015. (1R,3E,7E,11S,12R,14S)-11-Chloro-12-hydroxy3,7,15(17)-cembratrien-16,14-olide = 565. 4-Chloro-2,6,8-illudalatriene = 246. Chlorolissoclimide = 391. (2β,3E,6α,7α,8α,9β,14α)-6-Chloro-2,9,14trihydroxy-8-hydroxy-3,5(16),11(20)briaratrien-18,7-olide = 1076. Chondrosterin A = 319. Chondrosterin J = 322. Chromodorolide A = 520. Citronellol = 1. Cladiella peroxide = 825. Cladiellin = 826. Cladiellisin = 827. Cladielloide B = 828. Cladieunicellin A = 829. Cladieunicellin B = 830. Cladieunicellin C = 831. Cladieunicellin D = 832. Cladieunicellin E = 833. Cladieunicellin F = 834. Cladieunicellin G = 938. Cladieunicellin L = 835. Cladieunicellin M = 836. Cladieunicellin N = 837. Cladieunicellin O = 838. Cladieunicellin P = 839. Cladieunicellin Q = 840. Claviolide = 561. Clavukerin A = 234. Clavularin A = 235. Clavularin B = 236. 4(15)-Copaen-3α-ol = 350. Crassarine F = 562. Crassarine H = 563. Crassin acetate = 564.

Index 1 Compound Name and Synonym Index

Crassocolide H = 565. Crassocolide I = 566. Crassocolide J = 567. Crassocolide K = 568. Crassocolide L = 569. Crassocolide M = 570. Crassocolide N = 571. Crassocolide O = 572. Crassocolide P = 573. Crassolide = 574. Crassolide‡ = 575. Crassumol A = 576. Crassumol B = 577. Crassumol C = 578. Crassumolide A = 579. Crassumolide C = 580. Crassumolide G = 581. Crassumolide H = 582. Crassumolide I = 583. Cryptosphaerolide = 175. Culobophylin A = 584. Culobophylin B = 585. Culobophylin C = 586. Cupalaurenol = 124. Cupalaurenol acetate = 125. Curcudiol = 89. (–)-Curcuhydroquinone = 90. (+)-Curcuhydroquinone = 91. Curcumene = 92. (+)-Curcuphenol = 93. Curcuphenol = 94. Curcuquinol = 90. 10,15-Cyclo-1,20-epoxy-1,3(20),6,11(18)phytatetraene = 379. Cycloeudesmol = 159. Cyclolaurene = 129. Cyclolaurenol = 130. Cyclolaurenol acetate = 131. (4E,6E,8Z)-10,15-Cyclo-1,2,4,6,8,10phytahexaen-1-one = 380. Cyclosinularane = 349. D (+)-Dactylol = 328. 14-Deacetoxycalicophirin B = 841. 7-Deacetoxyolepupuane = 202. Deacetylisoparguerol = 486. Debromohamigeran A = 330.

399

Debromolaurinterol = 132. 7-[5-(Decahydro-4a-hydroxy-1,2,5,5tetramethyl-1-naphthalenyl)-3-methyl-2pentenyl]-3,7-dihydro-2,3-dimethyl-6Hpurin-6-one = 418. Dechloroelatol = 259. Dehydroambliol A = 379. Dehydrocurcuphenol = 95. 9,10-Dehydrofurodysinin = 251. 11-Dehydrosinulariolide = 587. DehydroxymethoxyeremofortineC = 165. Dendrocarbin J = 203. Dendrolasin = 68. Denticulatolide = 588. Deodactol = 96. 8-Deoxo-euplotin B = 84. Deoxosarcophine = 589. 4-Deoxyasbestinin A = 950. 4-Deoxyasbestinin C = 951. (1R,3R,4S,7E,11E)-(–)-14-Deoxycrassin = 590. (1S,3S,4R,7E,11E)-(+)-14-Deoxycrassin = 591. 11-Deoxydiaporthein A = 458. 12-Deoxygorgiacerodiol = 793. 2-Deoxylemnacarnol = 182. 2-Deoxy-7-O-methyllemnacarnol = 183. Deoxyparguerene = 487. Deoxyparguerol = 487. 13-Deoxyphomenone = 166. Deoxyprepacifenol = 260. 12,13-Deoxyroridin E = 135. 2ʹ,3ʹ-Deoxyroritoxin D = 136. 3α,14-Diacetoxycapnell-9 (12)-ene-8β,10α-diol = 315. 3α,8β-Diacetoxycapnell-9(12)-ene-10a-ol = 316. 1,4-Diacetoxy-2-[2-(2,2-dimethyl-6methylenecyclohexyl)ethyl]-1,3-butadiene = 79. 2α,11β-Diacetoxy-7-drimen-12-al = 210. (4β,6α,8Z,13α)-4,12-Diacetoxy-6,13-epoxy-8eunicellene = 842. 2,12-Diacetoxy-8,17-epoxy-9-hydroxy-5,13briaradien-18,7-olide = 1007. 6α,11β-Diacetoxy-14α-hydroxy-12-spongien-16one = 497. 3,19-diacetoxy-13(16),14-Spongiadiene = 498. 7α,11α-Diacetoxy-13-spongien-16-one = 499. 6α,11β-Diacetoxy-13-spongien-16-one = 500. 4,9-Diacetoxyudoteal = 357.

400

Index 1 Compound Name and Synonym Index

3,6-Diacetylcladiellisin = 843. Diacetyl-12-nor-8,11-drimanediol = 221. Diaporthein A = 459. Diaporthein B = 460. (E)-9,15-Dibromo-1,3(15)-chamigradien-7-ol = 261. (3(15)Z,6S,9S,10R)-10,15-Dibromo-1,3(15),7(14)chamigratrien-9-ol = 262. (3(15)E,6S,9S,10R)-10,15-Dibromo-1,3(15),7(14)chamigratrien-9-ol = 263. 4,10-Dibromo-3-chloro-7,9-chamigradien-1-ol = 264. 3,10-Dibromo-2-chloro-7(14)-chamigren-9-ol = 273. 1,4-Dibromo-5-chloro-2-(2-chloroethenyl)-1,5dimethylcyclohexane = 46. 2,10-Dibromo-3-chloro-7,8:9,10diepoxychamigrane = 265. 1,6-Dibromo-2-chloro-3(8)-ochtoden-4-ol = 28. (1E,6S*,8S*)-1,6-Dibromo-8-chloro-1,3ochtodiene = 29. (1E,4S*,6S*)-1,6-Dibromo-1,3(8)-ochtodien-4-ol = 30. (1E,3R,4S,5E,7S)-1,8-Dibromo-3,4,7-trichloro3,7-dimethyl-1,5-octadiene = 23. 2,4-Dichloro-1-(2-chloroethenyl)-1-methyl-5methylenecyclohexane = 40. Dichlorolissoclimide = 392. Dichotellide T = 1008. (1E,4R*,6S*)-1,6-Dibromo-1,3(8)-ochtodien-4-ol = 31. Dictyodendrillin A = 69. Dictyodendrillin B = 70. Dictyodendrillin C = 71. 3R,4R:7S,8S-Diepoxy-11,15(17)-cembradien16,14-olide = 570. (2S,3E,7S,8S,11E)-2,16:7,8-Diepoxy-1(15),3,11cembratriene = 589. (2R,3E,7S,8S,11E)-2,16:7,8-Diepoxy-1(15),3,11cembratriene = 592. (1R,7S,8S,11S,12S,13R)-3,6:11,12-Diepoxy-7,13diacetoxy-8-hydroxy-18-oxo-3,5,15cembratrien-20,10-olide = 593. (6β,7β,8α,10β,11βOH)-6,7:8,13-Diepoxy-11,12eremophilanediol = 177. Diepoxygorgiacerodiol = 792. 7,18:11,12-Diepoxy-2-(3-methylbutanoyl)-14acetoxy-5,7,11,17-briaratetraen-3-one = 1009.

Dihydroflexibilide = 595. 8,11-Dihydro-12-hydroxy isolaurene = 291. 2ʹ,3ʹ-Dihydro-2ʹ-hydroxyroridin H = 139. 8,9-Dihydro-linderazulene = 223. 9,10-Dihydro-linderazulene = 223. (–)12,13-Dihydro-14-methoxy-14deacetoxyspirodysin = 292. Dihydrosinuflexolide = 594. Dihydrosinularin = 595. Dihydrovaldivone A = 844. (1R,3R,4S,7E,11E,13S,14R)-3,4-Dihydroxy-13acetoxy-7,11,15(17)-cembratrien-16,14olide = 566. (1S,2S,3E,6S,7E,11E,14S)-6,14-Dihydroxy-3,7,11,15 (17)-cembratetraen-16,2-olide = 645. (1R,3R,4S,7E,11E,14R)-3,4-Dihydroxy-7,11,15(17)cembratrien-16,14-olide = 567. 15,16-Dihydroxy-4(18)-erythroxylen-3-one = 485. (2α,10β)-2,10-Dihydroxy-4(15),6,8-hirsutatrien5-one = 321. ent-15,18-Dihydroxylabd-8(17),13E-diene = 393. (E,E)-6-(6ʹ,7ʹ-dihydroxy-2ʹ,4ʹ-octadienoyl)strobilactone A = 204. 2,3-Dihydroxypropyl-farnesicate = 54. 17-(N,N-Dimethyl)-amino-3,7,11-cembratrien16,2-olid-19-oic acid = 596. 17-Dimethylaminolobohedleolide = 597. 1,2-Dimethyl-2-(4-methylphenyl)bicyclo[3.1.0] hexane = 129. 3-(4,8-Dimethyl-3,7-nonadienyl)furan = 68. (3E,7E)-5-(2,6-Dimethyl-1,5,7-octatrienyl)-3furancarboxylic acid = 72. 3,7-Dimethyl-6-octen-1-ol = 1. ent-14,15-Dinor-4(18)-cleroden-13-one = 457. Disydonol A = 97. Disydonol C = 98. Drechslerine D = 280. Drechslerine G = 281. 11,12-Drimanolide = 205. 7-Drimen-11-carboxylic acid 2,3dihydroxypropyl ester = 206. (5α,9β,10β)-8(12)-Drimen-11-ol acetate = 200. Durumhemiketalolide A = 598. Durumhemiketalolide B = 599. Durumhemiketalolide C = 600. Durumolide A = 601. Durumolide B = 602. Durumolide C = 603. Durumolide D = 604.

Index 1 Compound Name and Synonym Index

Durumolide E = 605. Durumolide P = 606. Durumolide Q = 607. E Echinoclerodane A = 436. Echinohalimane A = 419. Echinolabdane A = 394. Ehrenbergol A = 608. Ehrenbergol B = 609. Ehrenbergol C = 610. Ehrenberoxide A = 611. Ehrenberoxide B = 612. Ehrenberoxide C = 613. Elatol = 266. Eleganolone = 358. Eleganonal = 359. Eleutherobin = 845. Eleuthoside A = 846. Emblide = 614. (1S*,4R*,7S*,10R*)-1,7-Epidioxy-5-guaiene = 224. Epiparthenin = 237. (1R,3S,4S,7S,11E,14S)-3,4-Epoxy-7-acetoxy-8 (19),11,15(17)-cembratrien- 16,14-olide = 568. 6,13-Epoxy-12-acetoxy-3,8-eunicelladiene = 841. 4,7-Epoxy-3-acetoxy-8-hydroxy-11-oxo-15(17)cembren-16,12-olide = 736. (11β,16α)-Epoxy-16-acetoxy-,17-O-(3Methylbutanoyl)dihydroxy-15isocopalanal = 501. 10,11-Epoxycaulerpenyne = 55. 7,8-Epoxy-3,11,15-cembratrien-18-al = 646. 4,10-Epoxy-2,7,11-cembratriene = 615. 11,12-Epoxy-1,3,7-cembratrien-15-ol = 616. (1R,3E,7E,11S,12S,14S)-11,12-Epoxy-3,7,15(17)cembratrien-16,14-olide = 663. (3S,4R,7E,12E,14S)-3,4-Epoxy-1(15),7,12cembratrien-16,14-olide = 719. (1S,3R,4R,6E,8R,12S,13R,14R)-3,4-Epoxy-8,13diacetoxy-6,15(17)- cembradien-16,14-olide = 617. (1S,3R,4R,6E,8S,12S,13R,14R)-3,4-Epoxy-8,13diacetoxy-6,15(17)- cembradien-16,14-olide = 618.

401

11α,12α-Epoxy-(1R,7S,8S,10S,13R)-3,6:7,8diepoxy-13-acetoxy-18-oxo- 3,5,11,15cembratetraen-20,10-olide = 671. 3,4-Epoxy-13,19-dihydroxy-1,7-cembradiene9,14-dione = 628. (1R,3S,4S,6E,8S,11R,12R)-3,4-Epoxy-8,11dihydroxy-6,15(17)-cembradien-16,12-olide = 633. (1S,3R,4S,7R,12S,13R,14R)-4,7-Epoxy-3,13dihydroxy-8(19),15(17)- cembradien-16,14olide = 760. 3,4-Epoxy-13,18-dihydroxy-7,11,15(17)cembratrien-16,14-olide = 740. 4,7-Epoxy-3,8-dihydroxy-11-oxo-15(17)-cembren16,12-olide = 735. Epoxyeleganolone = 360. (6β,7β,8α,10β)-6,7-Epoxy-11(13)-eremophilene8,12-diol = 171. (6β,8α,10β)-8,12-Epoxy-7(11)-eremophilene6,13-diol = 178. (6β,8α,10β)-6,12-Epoxy-7(11)-eremophilene8,13-diol = 179. 8,12-Epoxy-3,7,11-eudesmatriene = 154. (6α,9β,12β,13α)-6,13-Epoxy-4(18),8(19)eunicelladiene-12-acetoxy-9-ol = 801. 6,13-Epoxy-4(18),8(19)-eunicelladiene-9,12diol = 827. 1,2-Epoxy-6,10-farnesadien-15,1-olide = 69. 9,13-Epoxy-1,3,7,9,11(13)-farnesapentaen-12-oic acid = 72. (5β,8αH)-15,16-Epoxy-13(16),14-halimadien-5-ol = 415. (1R,3S,4S,6E,8S,11R,12R)-3,4-Epoxy-8hydroperoxide–11-oxo-6,15(17)cembradien-16,12-olide = 632. (11β,16α)-Epoxy-12α-hydroxy-16α-acetoxy-17-O(3-methylbutanoyl)-15-isocopalanal = 502. (1R,3S,4R,7S,8R,12R)-4,8-Epoxy-3-hydroxy-7acetoxy-11-oxo-15(17)-cembren-16,12-olide = 692. (1S,3R,4S,7E,12R,13R,14R)-4,13-Epoxy-3hydroxy-7,15(17)-cembradien-16,14-olide = 639. 3,4-Epoxy-13-hydroxy-18-oxo-7,11,15(17)cembratrien-16,14-olide = 605. 2,3-Epoxy-1-hydroxy-6,10,14-phytatrien-13-one = 360.

402

Index 1 Compound Name and Synonym Index

(6β,9α)-11,12-Epoxy-11-ketone-7-drimene-6-O(5-carboxy-2E,4E-pentadienoyl)-6,9-diol = 207. 7,2-Epoxy-7methoxy-1(1)-nardosinene = 183. 7,12-Epoxy-1(10)-nardosinen-7-ol = 182. 8,17-Epoxy-4-octanoyloxy-2,9-diacetoxy11,12,16-trihydroxy-5,13-briaradien-18,7olide = 1131. Epoxyphomalin A = 208. Epoxyphomalin B = 209. 3α,4α-Epoxyprecapnell-9(12)-ene = 329. 11,12-Epoxypukalide = 619. Epoxyrarisetenolide = 293. (+)-11S,12S-Epoxysarcophytol A = 620. (1R,2S,3R,4S,5R,7E,9S,11E,14R)-3,4-Epoxy5,9,14-triacetoxy-7,11,15(17)-cembratrien16,2-olide = 574. (1R,3S,4R,7S,8R,11R,12R)-4,7-Epoxy-3,8,11trihydroxy-15(17)-cembren-16,12-olide = 695. Erectathiol = 282. EremofortineCa = 167. EremofortineCb = 168. Eremophildiendiol = 169. (6β,7βOH,8α)-11(13)-Eremophilene-6,7,8,12tetrol = 172. (6β,7αOH,8α)-11(13)-Eremophilene-6,7,8,12tetrol = 173. Erythrolide A = 1010. (+)-12-Ethoxycarbonyl-11Z-sarcophine = 621. 11β-Ethoxy-7α-hydroxy-8-drimen-12,11-olide = 203. Eunicenolide = 622. Eunicin = 623. Eupalmerin acetate = 624. 12,13-bisepi-Eupalmerin epoxide = 625. 12-epi-Eupalmerone = 626. Euplotin C = 83. Excavatoid E = 1011. Excavatoid F = 1012. Excavatoid O = 1013. Excavatoid P = 1014. Excavatolide A = 1015. Excavatolide B = 1016. Excavatolide C = 1017. Excavatolide D = 1018. Excavatolide E = 1019. Excavatolide F = 1020.

Excavatolide G = 1021. Excavatolide H = 1022. Excavatolide I = 1023. Excavatolide J = 1024. Excavatolide K = 1025. Excavatolide M = 1026. Excavatolide N = 1027. Excavatolide O = 1028. Excavatolide P = 1029. Excavatolide Q = 1030. Excavatolide V = 1031. Excavatolide W = 1032. Excavatolide Y = 1033. Excavatolide Z = 1034. F Farnesylacetone epoxide = 384. Flabellatene A = 627. Flabellatene B = 628. Flaccidoxide acetate = 629. Flexibilide = 730. Flexibilisolide C = 630. Flexilarin B = 631. Flexilarin D = 632. Flexilarin G = 633. Flexilin = 56. Fragilide C = 1035. Fragilide E = 1036. 12-epi-Fragilide G = 1037. Fragilide J = 1038. Frajunolide A = 1039. Frajunolide B = 1040. Frajunolide C = 1041. Frajunolide E = 1042. Frajunolide F = 1043. Frajunolide I = 1044. Frajunolide J = 1045. Frajunolide L = 1046. Frajunolide M = 1047. Frajunolide N = 1048. Frajunolide O = 1049. Frajunolide S = 1085. Fulvoplumierin = 48. Funicolide A = 1050. 7-epi-Funicolide A = 1051. Funicolide B = 1052. Funicolide C = 1053. Funicolide D = 1054.

Index 1 Compound Name and Synonym Index

Funicolide E = 1055. Furanodiene = 118. Furanoeudesm-3-ene = 154. G Gelidene = 36. Gemmacolide B = 1056. (+)-Gemmacolide B = 1057. Gemmacolide D = 1058. Gemmacolide G = 1059. Gemmacolide H = 1037. Gemmacolide I = 1060. Gemmacolide J = 1061. Gemmacolide K = 1062. Gemmacolide M = 1063. Gemmacolide N = 1064. Gemmacolide O = 1065. Gemmacolide P = 1066. Gemmacolide Q = 1067. Gemmacolide R = 1068. Gemmacolide S = 1069. Gemmacolide T = 1070. Gemmacolide U = 1071. Gemmacolide V = 1072. Gemmacolide W = 1073. Gemmacolide X = 1008. Gemmacolide Y = 1074. Geraniol = 2. (+)-Germacrene D = 115. Gifhornenolone A = 461. ent-Gloeosteretriol = 320. Gorgiabisazulene = 233. 11-Gorgiacerol = 793. Gracilin A = 521. Gracilin H = 522. Gracilin I = 523. Gracilin J = 524. Gracilin K = 525. Gracilin L = 526. Granosolide A = 634. Granosolide B = 635. (1α,8α,10α)-4,7(11)-Guaiadien-12,8-olide = 232. Guaiazulene = 225. Gyrosanolide B = 769. Gyrosanolide C = 770. H Halomon = 24. Hamigeran A = 331.

403

Hamigeran A ethyl ester = 332. Hamigeran B = 333. Hamigeran F = 334. Hamigeran G = 335. Hamigeran H = 336. Hamigeran I = 337. Hamigeran J = 338. Hamigeran K = 339. 10-epi-Hamigeran K = 340. Hamigeran L = 294. Hamigeran L methyl ester = 295. Haterumaimide A = 395. Haterumaimide B = 396. Haterumaimide C = 397. Haterumaimide D = 398. Haterumaimide E = 399. Haterumaimide F = 400. Haterumaimide G = 401. Haterumaimide H = 402. Haterumaimide I = 403. Haumanamide = 503. Hedaol A = 385. Hedaol B = 386. Hedaol C = 387. Heterogorgiolide = 160. Hirsutalin A = 847. Hirsutalin B = 848. Hirsutalin C = 849. Hirsutalin D = 850. Hirsutalin E = 851. Hirsutalin F = 852. Hirsutalin H = 853. Hirsutalin I = 854. Hirsutalin J = 855. Hirsutalin K = 856. Hirsutalin L = 857. Hirsutalin M = 858. Hirsutalin N = 859. Hirsutalin O = 860. Hirsutalin P = 861. Hirsutalin Q = 862. Hirsutalin R = 863. Hirsutanol A = 321. Hodgsonal = 210. Hydrallmanol A = 50. 7-Hydroxy-10-bromo-laurene = 127. γ-Hydroxybutenolide = 296. 8-Hydroxy-4,9-cadinadien-14-oic acid = 190. 6-Hydroxy-Δ7(14)-caulerpenyne = 53.

404

Index 1 Compound Name and Synonym Index

(1R,3E,7E,10S,11E,14S)-10-Hydroxy-3,7,11,15(17)cembratetraen-16,14-olide = 579. (3E,7S,11Z)-7-Hydroxy-3,11,15-cembratrien-20,8olide = 636. 4-Hydroxy-7,11,15(17)-cembratrien-16,3-olide = 591. Hydroxycolorenone = 226. 8-Hydroxydendrolasin = 73. (4α,5β,10α)-14-Hydroxy-1,11-eudesmadien-3one = 141. 1-Hydroxy-4-eudesmaen-12,6-olide = 152. 15-Hydroxy-2,6,10-farnesatrien-1,15-olide = 70. 1-Hydroxy-2,6,10-farnesatrien-15,1-olide = 71. 5-Hydroxygeranyllinalol = 361. 1-Hydroxy-4,10(14)-germacradien-12,6-olide = 116. 12-Hydroxy isolaurene = 297. ent-17-Hydroxykaur-15-en-3-one = 541. 7-Hydroxylaurene = 126. (−)-5-(Hydroxymethyl)-2-(2′,6′,6′trimethyltetrahydro-2H-pyran-2-yl)phenol = 99. (Z)-5-(Hydroxymethyl)-2-(6′-methylhept-2′-en2′-yl)phenol = 100. 6-O-(4-Hydroxy-4-methyl-2E-pentenoyl)-1,6dihydroxy-13-nor-4(15)-eudesmen-11-one = 158. 6-O-(4-Hydroxy-4-methyl-2E-pentenoyl)-1,6dihydroxy-13-nor-4,10(14)-germacradien11-one = 119. 6-O-(4-Hydroxy-4-methyl-2E-pentenoyl)-6hydroxy-13-nor-1,3-elemadien-11-one = 114. 6-O-(4-Hydroxy-4-methyl-2E-pentenoyl)-6hydroxy-1-oxo-13-nor-4,10(14)germacradien-11-one = 120. 6-Hydroxy-α-muurolene = 189. 19-Hydroxy-3-nor-2,3-seco-13(16),14spongiadien-2,4-olide = 504. 1-Hydroxy-2,6,10,14-phytatetraen-13-one = 358. 3-Hydroxy-1,4,6,10-phytatetraen-13-one = 362. 20-Hydroxy-2-phyten-1,20-olide = 355. (–)-6α-Hydroxypolyanthellin A = 864. 12‘-Hydroxyroridin E = 137. (–)-8-Hydroxysclerosporin = 190. Hymenin = 237.

I Ineleganolide = 778. Insulicolide A = 211. Irciniketene = 380. Isishippuric acid B = 298. Isobrasudol = 145. Isocopalendial = 505. (14αH)-12-Isocopalene-15,16-dial = 505. (14αH)-12-Isocopalen-15-oic acid(3-acetoxy-2hydroxypropyl) ester = 506. 12-Isocopalen-15-oic acid (2-acetoxy-3hydroxypropyl) ester = 507. 12-Isocopalen-15-oic acid2S,3-dihydroxypropyl ester = 508. Isocycloeudesmol = 159. Isoechinofuran = 227. Isofuranodiene = 118. Isohalomon = 25. Isolauraldehyde = 299. Δ7 (14)-Isonakafuran 9 = 300. Δ7 (14)-Isonakafuran 9 hydroperoxide = 301. Isoobtusol = 267. Isoobtusol acetate = 268. Isoparguerol = 488. Isoparguerol 16-acetate = 489. Isopimara-8(14),15-diene = 462. (2α,3β,7α)-8(14),15-Isopimaradiene-2,3,7,19tetrol 19-O-β-D-altropyranoside = 477. Isoplocamenone = 3. 7-Isopropyl-1,4-dimethylazulene = 225. Isorigidol = 269. Isosarcophinone = 637. Isosarcophytoxide = 638. Isospongiadiol = 509. (+)-10-Isothiocyanato-4-amorphene = 191. J Jeunicin = 639. 13αH,14βH-Jeunicin = 640. JNP711819-11 = 696. Junceellolide A = 1075. Junceellolide B = 1076. Junceellolide C = 1077. Junceellolide D = 1078. Junceellolide K = 1079. Junceellonoid C = 1080. Junceellonoid D = 1081. Juncenolide D = 1082. Juncenolide J = 1083.

Index 1 Compound Name and Synonym Index

Juncenolide K = 1084. Juncenolide M = 1085. Juncenolide N = 1086. Juncenolide O = 1087. Junceol A = 1088. Junceol A‡ = 146. Junceol B = 1089. Junceol C = 1090. Junceol D = 1091. Junceol E = 1092. Junceol F = 1093. Junceol G = 1094. Junceol H = 1095. Juncin E = 1096. Juncin O = 1097. Juncin P = 1098. Juncin Q = 1099. Juncin R = 1100. Juncin S = 1101. Juncin T = 1102. Juncin U = 1103. Juncin V = 1104. Juncin W = 1105. Juncin X = 1106. Juncin Y = 1107. Juncin Z = 1087. Juncin Z2 = 1108. Juncin ZI = 1109. Juncin ZII = 1110. K Kallolide A = 794. Kallolide B = 795. Kandenol A = 147. Kandenol B = 148. Kandenol C = 149. Kandenol D = 150. Kandenol E = 151. ent-Kaur-15-en-3β,17-diol = 542. Kericembrenolide A = 641. Kericembrenolide B = 642. Kericembrenolide C = 643. Kericembrenolide D = 644. Kericembrenolide E = 645. Klymollin C = 865. Klymollin D = 866. Klymollin E = 867. Klymollin F = 868. Klymollin G = 869.

Klymollin H = 870. Klymollin Q = 837. Klymollin W = 871. Klymollin X = 872. Klysimplexin B = 873. Klysimplexin G = 874. Klysimplexin H = 875. Klysimplexin J = 876. Klysimplexin K = 877. Klysimplexin L = 878. Klysimplexin M = 879. Klysimplexin N = 880. Klysimplexin Q = 881. Klysimplexin R = 882. Klysimplexin S = 883. Klysimplexin sulfoxide A = 884. Klysimplexin sulfoxide B = 885. Klysimplexin sulfoxide C = 886. Klysimplexin T = 887. Knightal = 646. Knightol = 647. Krempfielin A = 888. Krempfielin B = 889. Krempfielin C = 890. Krempfielin D = 891. Krempfielin I = 892. Krempfielin J = 893. Krempfielin K = 894. Krempfielin L = 895. Krempfielin M = 896. Krempfielin N = 897. Krempfielin O = 898. Krempfielin P = 899. Kumepaloxane = 84. L Labdane aldehyde TL95-8673A = 404. Labdane aldehyde TL95-8673B = 405. Labiatin B = 900. Laurecomin B = 270. Laurencianol = 381. Laurinterol = 133. allo-Laurinterol = 127. allo-Laurinterol acetate = 128. Lemnalol = 350. Libertellenone A = 463. Libertellenone C = 464. Libertellenone G = 465. Linderazulene = 228.

405

406

Index 1 Compound Name and Synonym Index

Litophynin A = 901. Litophynin B = 902. Litophynin C = 903. Litophynin D = 904. Litophynin E = 905. Litophynin F = 906. Litophynin H = 907. Litophynin I = 908. Litophynin I 3-acetate = 909. Litophynin J = 910. Litophynol A = 911. Litophynol B = 912. Lobocrassin A = 648. Lobocrassin B = 649. Lobocrassin C = 650. Lobocrassin D = 651. Lobocrassin E = 652. Lobocrassin F = 653. (7Z)-Lobocrassolide = 654. Lobocrassolide = 655. (7E)-Lobohedleolide = 656. (7Z)-Lobohedleolide = 657. Lobolide = 658. Lobomichaolide = 659. Lobophylin A = 660. Lobophylin B = 661. Lobophynin C = 662. Lobophytolide = 663. Lobophytone U = 664. Lobophytone V = 665. Lobophytone W = 666. Lobophytone X = 667. Lobophytone Y = 668. Lobophytone Z = 669. Lobophytone Z1 = 670. Lochmolin A = 239. Lochmolin B = 240. Lochmolin C = 241. Lochmolin D = 242. Lophotoxin = 671. Lophotoxin-analog I = 552. Lophotoxin-analog V = 551. M (6S,9R,10S)-Ma’ilione = 271. Macfarlandin A = 527. Macfarlandin B = 528. Macfarlandin D = 529. Mailiohydrin = 272.

Malayenolide A = 1111. Malayenolide B = 1112. Malayenolide C = 1113. Malayenolide D = 1114. Malonganenone C = 363. Malonganenone H = 364. Membranolide C = 530. Membranolide D = 531. Menelloide D = 117. Menelloide E = 229. Mertensene = 39. Mertensene 1 = 39. Merulin A = 275. Methoxycolorenone = 230. 10-Methoxy-6-guaien-4-ol = 231. (1α,7β,10β)-11-Methoxy-4-guaien-3-one = 230. Methyl 2-butanoyl-12-hydroxy-14-acetoxy-9oxo-5,7-briaradien-18-oate = 985. Methyl (1R,7S,8R,10S)-3,6:7,8-Diepoxy3,5,11,15-cembratetraen-20,10-olid-18-oate = 691. 11-O-Methyl-11,12-epoxy-11-drimanol = 212. 6-Methyl ether of litophynol B = 913. O-Methylguaianediol = 231. Methyl sartortuoate = 672. (+)-Methyl sydowate = 101. Michaolide L = 673. Michaolide M = 674. Michaolide N = 675. Michaolide O = 676. Michaolide P = 677. Michaolide Q = 678. (–)-Microcionin1 = 302. Microsphaeropsisin = 176. Minabein 8 = 1115. Muconomycin A = 140. Muquketone = 382. Muricellin = 914. Murrayanolide = 510. 4,9-Muuroladien-6-ol = 189. Myrocin A = 482. N Nakafuran 8 = 303. Nakafuran 9 = 304. (–)-Nephthenol‡ = 679. 1-Nor-2,19-phytanediyl-di-O-sulfate = 388. Norrisolide = 532. 3ʹ-Norspongiolactone = 533.

Index 1 Compound Name and Synonym Index

Notandolide = 693. NPR07H239A = 170. Nuiinoalide A = 1116. Nuiinoalide C = 1049. Nyalolide = 680. O Obtusol = 273. 1,3(8)-Ochtodien-5,6-diol = 32. 2Z,4-Ochtodien-1,6-diol = 33. Onchidal = 80. Ophirin = 915. Opuntial = 357. 3-Oxobolene = 102. 1-Oxocurcuphenol = 103. 13-Oxo-2,6,10,14-phytatetraen-1-al = 359. 11-Oxo-5-silphiperfolen-13-oic acid = 323. Oxytoxin 1 = 57. P Pachycladin A = 916. Pachycladin B = 917. Pachycladin C = 918. Pachycladin D = 919. Pachyclavulariolide F = 681. Pachyclavulariolide I = 682. Pachyclavulariolide J = 683. Pacifenol = 274. Pacifigorgiol = 286. Paesslerin A = 342. Paesslerin B = 343. Palmadorin A = 437. Palmadorin B = 438. Palmadorin C = 439. Palmadorin D = 440. Palmadorin E = 441. Palmadorin F = 442. Palmadorin G = 443. Palmadorin H = 444. Palmadorin I = 445. Palmadorin J = 446. Palmadorin K = 447. Palmadorin L = 448. Palmadorin M = 449. Palmadorin N = 450. Palmadorin O = 451. Palmadorin P = 452. Palmadorin Q = 453. Palmadorin R = 454.

Palmadorin S = 455. Pannosane = 287. Pannosanol = 288. Parahigginic acid = 104. Parahigginin = 105. Parahigginol B = 106. Parahigginol C = 107. Parahigginol D = 108. Parahigginone = 109. Paralemnolide A = 184. Paralemnolin M = 185. Paralemnolin N = 186. Paralemnolin Q = 187. Paralemnolin S = 188. 9(11)-Pargueren-16-al = 490. Parguerene = 491. Parguerol = 491. Parguerol 16-acetate = 492. Pavidolide A = 684. Pavidolide B = 685. Pavidolide C = 686. Pavidolide D = 687. Pavidolide E = 688. Peribysin A = 171. Peribysin B = 177. Peribysin C = 178. Peribysin D = 179. Peribysin E = 283. Peribysin F = 172. Peribysin G = 173. Peribysin H = 180. Peribysin I = 181. Peribysin J = 174. Petronigrione = 689. 1,18-Phytanediyl disulfate = 365. (4E,6E,10E)-1,4,6,10,14-Phytapentaen-3-ol = 366. Picrotin = 284. Picrotoxinin = 285. Pinnatin A = 779. Pinnatin B = 780. Pinnatin C = 781. Pinnatin D = 782. Pinnatin E = 783. Plocamene D = 40. Plocamene D’ = 41. epi-Plocamene D = 42. Plocamenone = 4. Plumericin = 49.

407

408

Index 1 Compound Name and Synonym Index

(−)-Polyanthelin A = 920. (+)-Polyanthelin A = 921. Polyanthellin A = 922. Polygodial = 213. Popolohuanone F = 456. Praelolide = 1117. 3-Precapnellen-6β-ol = 328. Preraikovenal = 58. Presinularolide B = 603. Preuplotin = 59. Pseudoplexaurol = 690. Pseudopteradiene = 796. Pseudopteradienoic acid = 797. Pseudopteranoic acid = 798. Pseudopterolide = 799. 11-Pseudopteronol = 793. 12-Ptilosarcenol = 1118. Ptilosarcenone = 1119. Ptilosarcone = 1120. Pukalide = 691. Purpurogemutantidin = 214. Purpurogemutantin = 215. Q Quadrone = 324. Querciformolide A = 692. Querciformolide B = 693. Querciformolide C = 694. Querciformolide D = 695. R Raikovenal = 305. Rarisetenolide = 306. epi-Rarisetenolide = 307. Renillafoulin A = 1115. Renillafoulin B = 1121. Renillafoulin C = 1122. Rhipocephalin = 60. Rhipocephenal = 61. Robustolide J = 1077. Roridin Q = 138. Roridin R = 139. Rumphellaone A = 123. S Sarcocrassocolide A = 697. Sarcocrassocolide B = 698. Sarcocrassocolide C = 699. Sarcocrassocolide D = 700.

Sarcocrassocolide E = 701. Sarcocrassocolide F = 702. Sarcocrassocolide G = 703. Sarcocrassocolide H = 704. Sarcocrassocolide I = 705. Sarcocrassocolide J = 706. Sarcocrassocolide K = 707. Sarcocrassocolide L = 708. Sarcocrassocolide M = 709. Sarcocrassocolide N = 710. Sarcocrassocolide O = 711. Sarcocrassolide = 712. Sarcocrassolide B = 626. Sarcodictyin A = 923. Sarcodictyin B = 924. Sarcoglaucol = 713. Sarcolactone A = 714. Sarcophine = 715. Sarcophinone = 716. Sarcophyocrassolide B = 626. Sarcophytol A = 717. Sarcophytol B = 718. Sarcophytolide‡ = 719. Sarcophytol M = 720. Sarcophytonin G = 578. Sarcotal acetate = 784. Sarcotol = 785. Sarcrassin A = 721. Sarcrassin B = 722. Sarcrassin D = 723. Sarcrassin E = 724. Scabralin A = 192. Sclerophytin A = 925. Sclerophytin A methyl ether = 926. Sclerophytin B = 927. Sclerophytin F = 928. (+)-Sclerosporin = 193. Scopararane B = 466. Scopararane C = 467. Scopararane D = 468. Scopararane E = 469. Scopararane F = 470. Scopararane G = 471. Simplexin A = 929. Simplexin D = 930. Simplexin E = 931. Simplexin M = 932. Simplexin N = 933. Simplexin O = 934.

Index 1 Compound Name and Synonym Index

Simplexin P = 935. Simplexin Q = 936. Simplexin R = 937. Simplexin S = 938. Sinuflexibilin = 725. Sinuflexolide = 726. Sinugibberol = 727. Sinularcasbane B = 728. Sinularcasbane E = 729. Sinularianin C = 244. Sinularianin D = 245. Sinularianin E = 62. Sinularianin F = 74. Sinularin = 730. (–)-Sinulariol B = 731. Sinulariolide = 732. 11-epi-Sinulariolide = 733. Sinulariol J = 734. Sinulariolone = 735. Sinulariolone 3-acetate = 736. Sinulariol P = 737. Sinulariol Z = 738. Sinularolide B = 739. Sinularolide C = 740. 5-epi-Sinuleptolide acetate = 741. Sinumaximol B = 742. Sinumaximol C = 743. Solenolide A = 1123. (−)-Solenopodin C = 939. Spathulenol‡ = 243. Sphaerococcenol A = 954. Sphaerolabdiene-3,14-diol = 407. Spirotubipolide = 161. Stecholide A = 1124. Stecholide B = 1125. Stecholide H = 1126. Steperoxide B = 275. Strobilactone A = 216. Stylatulide = 1127. Styxenol A = 367. Subergorgic acid = 323. Suberosanone = 344. Suberosenol A = 345. Suberosenol A acetate = 346. Suberosenol B = 347. Suberosenol B acetate = 348. Suberosenone = 325.

409

(–)-Sydonic acid = 110. (+)-Sydonic acid = 111. (–)-Sydonol = 112. (+)-Sydowic acid = 113. T Tagalsin Q = 483. Tagalsin R = 484. Tagalsin U = 485. Talaperoxide A = 276. Talaperoxide B = 277. Talaperoxide C = 278. Talaperoxide D = 279. Tanyolide A = 81. Tanyolide B = 82. Tavacfuran = 75. T-cadinthiol = 194. Tedanol = 472. Terrecyclic acid A = 326. Terrecyclol = 327. Tetrahydroaplysulphurin 1 = 518. Thespone = 195. Thioflexibilolide A = 744. Thuridillin A = 368. Thuridillin B = 383. 2α,8β,13-Triacetoxycapnell-9(12)-ene-10α-ol = 317. 3α,8β,14-Triacetoxycapnell-9(12)-ene-10a-ol = 318. (1S,2S,3E,6S,7E,10S,11E,14S)-6,10,14Triacetoxy-3,7,11,15(17)-cembratetraen16,2-olide = 745. Triangulene A = 746. Triangulene B = 747. 1,6,8-Tribromo-2-chloro-3(8)-ochtodene = 34. (2R,3E,6R,7S)-1,1,7-Tribromo-2,6,8-trichloro3,7-dimethyl-3-octene = 26. (1S,2R,4R,5S)-1,2,4-Trichloro-5-(2-chloroethenyl)1,5-dimethylcyclohexane = 43. (1S,2R,4S,5S)-1,2,4-Trichloro-5-(2-chloroethenyl)1,5-dimethylcyclohexane = 44. (1S,2R,4R,5R)-1,2,4-Trichloro-5-(2-chloroethenyl)1,5-dimethylcyclohexane = 45. 1,6,8-Trichloro-2,4-ochtodadiene = 35. 3,4,11-Trihydroxy-7,15(17)-cembradien-16,12olide = 557. 3,5,8-Trimethylazuleno[6,5-b]furan = 228. (3Z,5E)-3,7,11-Trimethyl-9-oxododeca-1,3,5triene = 63.

410

Index 1 Compound Name and Synonym Index

(3E,5E)-3,7,11-Trimethyl-9-oxododeca-1,3,5triene = 64. (2E,4E,7Z)-2,6,10-Trimethylundeca-2,4,7,9tetraenal = 65. (2E,4E)-2,6,10-Trimethylundeca-2,4,9-trienal = 66. Tubipofuran = 155. Tubipolide B = 156. Tubipolide G = 157. Tubiporein = 1128. U Udoteal = 369. Uproeunicin = 748. Uproeuniolide = 749. Uprolide A acetate = 750. 8-epi-Uprolide A acetate = 751. Uprolide B = 752. 8-epi-Uprolide B = 753. Uprolide B acetate = 754. 8-epi-Uprolide B acetate = 755. Uprolide C = 756. Uprolide C acetate = 757. 7-epi-Uprolide C acetate = 758. 7-epi-Uprolide C diacetate = 759. Uprolide D = 760. Uprolide D acetate = 761. 12,13-bisepi-Uprolide D acetate = 762. Uprolide E acetate = 763. Uprolide F diacetate = 764. Uprolide G acetate = 765. Uprolide H = 766. Ustusolate A = 217.

Ustusolate C = 218. Ustusolate E = 219. V Valdivone A = 940. Valdivone B = 941. Verrol 4-acetate = 134. Verrucarin A = 140. Verrucosin 1 = 511. Verrucosin 2 = 536. Verrucosin 3 = 534. Verrucosin 4 = 370. Verrucosin 5 = 406. Verrucosin 6 = 512. Verrucosin 7 = 513. Verrucosin 8 = 535. Verrucosin 9 = 514. Verrucosin A = 515. Verrucosin B = 516. Violide A = 1129. Violide B = 1130. Violide N = 1131. Virescenoside A = 473. Virescenoside B = 474. Virescenoside C = 475. Virescenoside M = 476. Virescenoside N = 477. Virescenoside O = 478. Virescenoside P = 479. Virescenoside Q = 480. Y Yalongene A = 767. Yalongene B = 768.

Index 2 Compound Molecular Formula Index The Molecular Formula Index of HAMNP Volume 1 lists the molecular formulae of all 1,131 active isolated compounds from marine organisms given in the HAMNP Volume 1 in Hill convention order. Under a bold formula, all related compound names following code numbers are listed in the code number order too. C10 C10H10BrCl5 – 3,4-erythro-1-Bromo-7-dichloromethyl-3methyl-3,4,8-trichloro-1(E),5(E),7(E)octatriene, 15. C10H11Cl3O – Cartilagineal, 22. C10H12BrCl3O – Isoplocamenone, 3. – Plocamenone, 4. C10H12BrCl5 – (1E,3R,4S,5E)-8-Bromo-1,3,4,7-tetrachloro7-chloromethyl-3-methyl-1,5-octadiene, 20. C10H13BrCl2 – Plocamene D’, 41. C10H13BrCl4 – 8-Bromo-1,3,4,7-tetrachloro-3,7-dimethyl-1,5octadiene, 21. C10H13Br2Cl – (1E,6S*,8S*)-1,6-Dibromo-8-chloro-1,3ochtodiene, 29. C10H13Br2Cl3 – (1E,3R,4S,5E,7S)-1,8-Dibromo-3,4,7-trichloro3,7-dimethyl-1,5-octadiene, 23. – 4-Bromo-5-bromomethyl-1-(2-chloroethenyl)2,5-dichloro-1-methylcyclohexane, 37. C10H13Cl3 – 1,6,8-Trichloro-2,4-ochtodadiene, 35. – 4-Chloro-5-(2-chloroethenyl)-1-chloromethyl5-methylcyclohexene, 38. – Plocamene D, 40. – epi-Plocamene D, 42. C10H14BrCl – Z-3-Bromomethylene-2-chloro-7-methyl-1,6octadiene, 18. C10H14BrCl3 – 3-(Bromomethyl)-2,3,6-trichloro-7-methyl-1,6octadiene, 19. – 4-Bromo-1,6,8-trichloro-2-ochtodene, 27. – Mertensene, 39.

C10H14Br2Cl2 – 6-Bromo-3-(bromomethyl)-2,3-dichloro-7methyl-1,6-octadiene, 13. – 1,4-Dibromo-5-chloro-2-(2-chloroethenyl)-1,5dimethylcyclohexane, 46. C10H14Br2O – (1E,4S*,6S*)-1,6-Dibromo-1,3(8)-ochtodien-4ol, 30. – (1E,4R*,6S*)-1,6-Dibromo-1,3(8)-ochtodien-4ol, 31. C10H14Br3Cl – 1,6,8-Tribromo-2-chloro-3(8)-ochtodene, 34. C10H14Br3Cl3 – (2R,3E,6R,7S)-1,1,7-Tribromo-2,6,8-trichloro3,7-dimethyl-3-octene, 26. C10H14Cl4 – Aplysiaterpenoid A, 36. – (1S,2R,4R,5S)-1,2,4-Trichloro-5-(2-chloroethenyl)-1,5-dimethylcyclohexane, 43. – (1S,2R,4S,5S)-1,2,4-Trichloro-5-(2-chloroethenyl)-1,5-dimethylcyclohexane, 44. – (1S,2R,4R,5R)-1,2,4-Trichloro-5-(2-chloroethenyl)-1,5-dimethylcyclohexane, 45. C10H15BrCl2 – 3-(Bromomethyl)-2,3-dichloro-7-methyl-1,6octadiene, 17. C10H15BrCl2O – Aplysiapyranoid C, 11. – Aplysiapyranoid D, 12. C10H15Br2ClO – Aplysiapyranoid A, 9. – Aplysiapyranoid B, 10. – 1,6-Dibromo-2-chloro-3(8)-ochtoden-4-ol, 28. C10H15Br2Cl3 – Halomon, 24. – Isohalomon, 25. C10H15Br3Cl2 – Anverene, 8. C10H16BrCl – 3-Bromomethyl-3-chloro-7-methyl-1,6-octadiene, 16.

412

Index 2 Compound Molecular Formula Index

C10H16Br2Cl2 – 6-Bromo-3-bromomethyl-3,7-dichloro-7methyl-1-octene, 14. C10H16O2 – 1,3(8)-Ochtodien-5,6-diol, 32. – 2Z,4-Ochtodien-1,6-diol, 33. C10H18O – Geraniol, 2. C10H20O – Citronellol, 1. C10H20O4

C14H20O4 – Talaperoxide C, 278. – Talaperoxide D, 279. C14H22O – (2E,4E)-2,6,10-Trimethylundeca-2,4,9-trienal, 66. C14H22O4 – Steperoxide B, 275. – Isishippuric acid B, 298. C14H24O3 – Chabranol, 122.

C11 C11H8O4 – Cerbinal, 47.

C15 C15H12O3 – Thespone, 195. C15H14O6 – Plumericin, 49. C15H15O – Linderazulene, 228. C15H16O – 8,9-Dihydro-linderazulene, 223. C15H16O6 – Picrotoxinin, 285. C15H17NO5 – Alcyopterosin E, 248. C15H18 – Guaiazulene, 225. C15H18O – Tubipofuran, 155. – Isoechinofuran, 227. – 9,10-Dehydrofurodysinin, 251. – Isolauraldehyde, 299. C15H18O2 – Tavacfuran, 75. – Tubipolide B, 156. C15H18O3 – (3E,7E)-5-(2,6-Dimethyl-1,5,7-octatrienyl)- 3furancarboxylic acid, 72. – Parahigginol D, 108. – Hirsutanol A, 321. C15H18O4 – Menelloide E, 229. – Hymenin, 237. C15H18O7 – Picrotin, 284. C15H19BrO – Cupalaurenol, 124. – allo-Laurinterol, 127.

C12 C12H17BrCl2O2 – (3Z,5E)-1-Acetoxy-8-bromo-4,7dichloro-3,7-dimethylocta3,5-diene, 5. C12H17Cl3O3 – (7E)-1-Acetoxy-8-chloro-7-(dichloromethyl)-3methyloct-7-en-4-one, 6. – (7Z)-1-Acetoxy-8-chloro-7-(dichloromethyl)-3methyloct-7-en-4-one, 7. C12H18 – Clavukerin A, 234. C12H18O2 – Clavularin A, 235. – Clavularin B, 236. C12H20BrClO – Kumepaloxane, 84. C12H24O5 – Talaperoxide A, 276. – Talaperoxide B, 277. C14 C14H12O4 – Fulvoplumierin, 48. C14H15ClO4 – Chloroacetoxyhydroxyeremophiltrienone, 164. C14H19BrO2 – (6S,9R,10S)-Ma’ilione, 271. C14H20O – (2E,4E,7Z)-2,6,10-Trimethylundeca-2,4,7,9tetraenal, 65.

Index 2 Compound Molecular Formula Index

– Cyclolaurenol, 130. – Laurinterol, 133. C15H19NO4 – Alcyopterosin C, 247. C15H20 – Cyclolaurene, 129. C15H20Br2O – (3(15)Z,6S,9S,10R)-10,15-Dibromo-1,3(15), 7(14)-chamigratrien-9-ol, 262. – (3(15)E,6S,9S,10R)-10,15-Dibromo-1,3(15), 7(14)-chamigratrien-9-ol, 263. C15H20O – Dehydrocurcuphenol, 95. – Furanodiene, 118. – 7-Hydroxylaurene, 126. – Debromolaurinterol, 132. – Atractylon, 153. – Furanoeudesm-3-ene, 154. – 12-Hydroxy isolaurene, 297. – Δ7 (14)-Isonakafuran 9, 300. – Nakafuran 8, 303. – Nakafuran 9, 304. C15H20O2 – 3-Oxobolene, 102. – 1-Oxocurcuphenol, 103. – Parahigginone, 109. – Americanolide D, 232. – Rarisetenolide, 306. – epi-Rarisetenolide, 307. – Chondrosterin A, 319. C15H20O3 – Rhipocephenal, 61. – Menelloide D, 117. – 13-Deoxyphomenone, 166. – Epoxyrarisetenolide, 293. – γ-Hydroxybutenolide, 296. – Subergorgic acid, 323. – Quadrone, 324. – Terrecyclic acid A, 326. C15H20O4 – Abscisic acid, 76. – (+)-Sydowic acid, 113. – Antibiotic JBIR 28, 163. C15H21BrO3 – Aplysistatin, 77. C15H21Br2ClO – Deoxyprepacifenol, 260. – 4,10-Dibromo-3-chloro-7,9-chamigradien1-ol, 264.

413

C15H21Br2ClO2 – 2,10-Dibromo-3-chloro-7,8:9,10-diepoxychamigrane, 265. – Pacifenol, 274. C15H21Cl – Alcyopterosin A, 246. C15H21NO4 – Alcyopterosin H, 249. C15H22 – Curcumene, 92. C15H22BrClO – Elatol, 266. C15H22Br2O – (E)-9,15-Dibromo-1,3(15)-chamigradien-7-ol, 261. C15H22Br2O2 – Mailiohydrin, 272. C15H22O – Dendrolasin, 68. – (+)-Curcuphenol, 93. – Curcuphenol, 94. – 8,11-Dihydro-12-hydroxy isolaurene, 291. – (–)-Microcionin1, 302. – Suberosenone, 325. C15H22O2 – 8-Hydroxydendrolasin, 73. – (–)-Curcuhydroquinone, 90. – (+)-Curcuhydroquinone, 91. – (Z)-5-(Hydroxymethyl)-2-(6′-methylhept-2′-en2′-yl)phenol, 100. – Ainigmaptilone A, 141. – (+)-Sclerosporin, 193. – Polygodial, 213. – Lochmolin A, 239. – Terrecyclol, 327. C15H22O3 – Dictyodendrillin A, 69. – Dictyodendrillin B, 70. – Dictyodendrillin C, 71. – (−)-5-(Hydroxymethyl)-2-(2′,6′,6′-trimethyltetrahydro-2H-pyran-2-yl)phenol, 99. – Parahigginin, 105. – 1-Hydroxy-4,10(14)-germacradien-12, 6-olide, 116. – Kandenol E, 151. – 1-Hydroxy-4-eudesmaen-12,6-olide, 152. – Paralemnolin Q, 187. – Paralemnolin S, 188. – (–)-8-Hydroxysclerosporin, 190.

414

Index 2 Compound Molecular Formula Index

– Sinularianin D, 245. – Drechslerine D, 280. – Aignopsanoic acid, 289. – Chondrosterin J, 322. C15H22O4 – (–)-Sydonic acid, 110. – (+)-Sydonic acid, 111. – Strobilactone A, 216. C15H22O5 – Paralemnolide A, 184. C15H22S – Erectathiol, 282. C15H23Br – 10-Bromo-2,7(14)-chamigradiene, 252. C15H23BrO – 10-Bromo-2,7-chamigradien-9-ol, 254. – (6R,9R,10S)-10-Bromo-9-hydroxy-chamigra2,7(14)-diene, 256. – Dechloroelatol, 259. – Laurecomin B, 270. C15H23BrO2 – 10-Bromo-1,7(14)-chamigradiene-3, 9-diol, 253. – 10-Bromo-7α,8α-epoxychamigr-1-en-3-ol, 255. – Isorigidol, 269. C15H23Br2ClO – Cartilagineol, 257. – Chamigrane epoxide, 258. – Isoobtusol, 267. – Obtusol, 273. C15H24 – (+)-Germacrene D, 115. – (+)-Alloaromadendrene, 238. – 3 (15)-Africanene, 308. – 9(12)-Capnellene, 312. – Cyclosinularane, 349. C15H24BrClO – Pannosane, 287. – Pannosanol, 288. C15H24O – (3Z,5E)-3,7,11-Trimethyl-9-oxododeca-1,3,5triene, 63. – (3E,5E)-3,7,11-Trimethyl-9-oxododeca-1,3,5triene, 64. – 6-Hydroxy-α-muurolene, 189. – Spathulenol‡, 243. – 9 (12)-Capnellen-8β-ol, 314. – 3α,4α-Epoxyprecapnell-9(12)-ene, 329.

– Suberosanone, 344. – Suberosenol A, 345. – Suberosenol B, 347. – Lemnalol, 350. C15H24O2 – Preraikovenal, 58. – Aspergiterpenoid A, 86. – Curcudiol, 89. – Eremophildiendiol, 169. – 2-Deoxylemnacarnol, 182. – Scabralin A, 192. – 11,12-Drimanolide, 205. – (1S*,4R*,7S*,10R*)-1,7-Epidioxy-5-guaiene, 224. – Hydroxycolorenone, 226. – Raikovenal, 305. – Capnell-9 (12)-ene-8β,10α-diol, 313. C15H24O3 – (–)-Sydonol, 112. – Rumphellaone A, 123. – Kandenol A, 147. – Peribysin A, 171. – Peribysin C, 178. – Peribysin D, 179. – Lochmolin C, 241. – Lochmolin D, 242. – Drechslerine G, 281. C15H24O4 – Kandenol B, 148. – Kandenol D, 150. – Peribysin B, 177. – Peribysin H, 180. – Peribysin I, 181. C15H24O5 – Kandenol C, 149. C15H25BrO – Brasudol, 142. – 2-Bromo-11-eudesmen-5-ol, 143. – 3-Bromo-11-eudesmen-5-ol, 144. – Isobrasudol, 145. C15H25Br2ClO – Caespitane, 87. C15H25Br2ClO2 – Caespitol, 88. – Deodactol, 96. C15H26O – Arenaran A, 78. – Cycloeudesmol, 159. – (+)-Albicanol, 199.

Index 2 Compound Molecular Formula Index

– Pacifigorgiol, 286. – Africanol, 309. – (+)-Dactylol, 328. C15H26O2 – Albican-11,14-diol, 198. C15H26O3 – ent-Gloeosteretriol, 320. C15H26O4 – Peribysin F, 172. – Peribysin G, 173. C15H26O5 – Peribysin J, 174. C15H26S – T-cadinthiol, 194. C16 C16H20O3 – Heterogorgiolide, 160. C16H20O4 – Parahigginic acid, 104. C16H22O4 – (+)-Methyl sydowate, 101. – Microsphaeropsisin, 176. – Sinularianin C, 244. C16H24O3 – Sinularianin F, 74. – Aignopsanoic acid methyl ester, 290. C16H24O4 – Sinularianin E, 62. – Δ7 (14)-Isonakafuran 9 hydroperoxide, 301. C16H25NS – (+)-10-Isothiocyanato-4-amorphene, 191. C16H26O2 – (–)-Anthoplalone, 121. – 2-Deoxy-7-O-methyllemnacarnol, 183. – 14(4→5),15(10→9)-Bisabeo-3-drimene-11carboxylic acid, 220. – Methoxycolorenone, 230. – (–)12,13-Dihydro-14-methoxy-14-deacetoxyspirodysin, 292. C16H26O4 – Peribysin E, 283. C16H28O2 – 11-O-Methyl-11,12-epoxy-11-drimanol, 212. – 10-Methoxy-6-guaien-4-ol, 231. C17 C17H18O4 – Tubipolide G, 157.

415

C17H20O5 – Spirotubipolide, 161. C17H21BrO2 – Cupalaurenol acetate, 125. – allo-Laurinterol acetate, 128. – Cyclolaurenol acetate, 131. C17H22O4S – 14-Acetylthioxyfurodysinin lactone, 250. C17H22O6 – EremofortineCa, 167. – EremofortineCb, 168. C17H24O3 – Onchidal, 80. C17H24O4 – Euplotin C, 83. – Parahigginol B, 106. – 3-Acetoxy-9,7(11)-dien-7α-hydroxy-8oxoeremo- philane, 162. – 11-Acetoxy-8-drimen-12,11-olide, 196. C17H25Br2ClO2 – Isoobtusol acetate, 268. C17H26O2 – (3E)-6-Acetoxy-3,11-dimethyl-7-methylidendodeca-1,3,10-triene, 51. – 3-Acetoxy-E-γ-bisabolene, 85. – Paesslerin A, 342. – Suberosenol A acetate, 346. – Suberosenol B acetate, 348. C17H26O3 – Parahigginol C, 107. – 7-Deacetoxyolepupuane, 202. – 8β-Acetoxycapnell-9 (12)-ene-10α-ol, 310. C17H26O4 – Dendrocarbin J, 203. C17H26O5 – 3β-Acetoxycapnellene-8β,10α, 14-triol, 311. C17H28O2 – (+)-Albicanol acetate, 200. C17H28O3 – Junceol A‡, 146. C17H30O2 – Lochmolin B, 240. C18 C18H21BrO3 – Hamigeran B, 333. C18H22Br2O3 – 4-Bromohamigeran K, 341.

416

Index 2 Compound Molecular Formula Index

C18H23BrO3 – Hamigeran K, 339. – 10-epi-Hamigeran K, 340. C18H24O6 – Dehydroxymethoxyeremofortine C, 165. C18H26O2 – Tagalsin Q, 483. C18H26O4 – Paesslerin B, 343. C18H30O – Muquketone, 382. – ent-14,15-Dinor-4(18)-cleroden13-one, 457. C18H30O2 – Farnesylacetone epoxide, 384. – Hedaol A, 385. – Hedaol B, 386. – Hedaol C, 387. C18H30O4 – 2,3-Dihydroxypropyl-farnesicate, 54. – 7-Drimen-11-carboxylic acid 2,3dihydroxypropyl ester, 206. – Diacetyl-12-nor-8,11-drimanediol, 221. C19 C19H22O5 – Ineleganolide, 778. C19H23BrO3 – Hamigeran G, 335. C19H24O5 – Oxytoxin 1, 57. C19H24O6 – Gyrosanolide B, 769. C19H25BrO4 – Hamigeran I, 337. C19H26O4 – 19-Hydroxy-3-nor-2,3-seco-13(16),14-spongiadien-2,4-olide, 504. C19H26O5 – Preuplotin, 59. C19H28O2 – Gifhornenolone A, 461. C19H28O4 – Flexilin, 56. – 1,4-Diacetoxy-2-[2-(2,2-dimethyl-6-methylenecyclohexyl)ethyl]-1,3-butadiene, 79. – Paralemnolin M, 185. – Paralemnolin N, 186. – Tagalsin R, 484.

C19H28O5 – Hodgsonal, 210. – 3α,8β-Diacetoxycapnell-9(12)-ene-10a-ol, 316. C19H28O6 – 3α,14-Diacetoxycapnell-9 (12)-ene-8β,10αdiol, 315. C19H30O3 – Sinulariol P, 737. C19H40O8S2 – 1-Nor-2,19-phytanediyl-di-O-sulfate, 388. C20 C20H20O5 – Pseudopteradienoic acid, 797. C20H22O5 – Pseudopteranoic acid, 798. C20H22O6 – Myrocin A, 482. C20H24O3 – Kallolide B, 795. C20H24O4 – Pinnatin A, 779. – Kallolide A, 794. C20H24O5 – Pinnatin C, 781. – Pinnatin D, 782. – Pinnatin E, 783. C20H24O6 – Bipinnapterolide B, 787. C20H25BrO5 – Hamigeran A, 331. – Hamigeran J, 338. C20H26O – Irciniketene, 380. C20H26O3 – Crassocolide O, 572. C20H26O4 – Crassocolide N, 571. – (7E)-Lobohedleolide, 656. – (7Z)-Lobohedleolide, 657. – Pavidolide B, 685. C20H26O5 – Debromohamigeran A, 330. – Durumolide E, 605. – Flexibilisolide C, 630. C20H26O6 – Gyrosanolide C, 770. C20H27BrO5 – Hamigeran L, 294.

Index 2 Compound Molecular Formula Index

C20H27Cl2NO4 – Haterumaimide B, 396. – Haterumaimide C, 397. – Haterumaimide D, 398. C20H28ClNO4 – Haterumaimide G, 401. – Haterumaimide H, 402. – Haterumaimide I, 403. C20H28O2 – (1S,2S,3E,7E,11E)-3,7,11,15-Cembratetraen17,2-olide, 559. C20H28O3 – Scopararane C, 467. – Crassolide‡, 575. – Crassumolide A, 579. – Isosarcophinone, 637. – Lobophytolide, 663. – Sarcocrassolide, 712. – Sarcolactone A, 714. – Sarcophine, 715. – Sarcophinone, 716. – Sarcophytolide‡, 719. C20H28O4 – Libertellenone A, 463. – Scopararane D, 468. – Isospongiadiol, 509. – Crassocolide M, 570. – Crassumolide I, 583. – 11-Dehydrosinulariolide, 587. – Durumolide C, 603. – 12-epi-Eupalmerone, 626. – Kericembrenolide E, 645. – Sarcocrassocolide C, 699. – Sarcocrassocolide D, 700. – Sarcocrassocolide K, 707. – Sarcocrassocolide L, 708. – Uproeuniolide, 749. C20H28O5 – 6-O-(4-Hydroxy-4-methyl-2E-pentenoyl)-6hydroxy-1-oxo-13-nor-4,10(14)-germacradien-11-one, 120. – Libertellenone C, 464. – Scopararane E, 469. – Durumhemiketalolide A, 598. – Sarcocrassocolide J, 706. – Sarcocrassocolide O, 711. – Sinularolide B, 739. – Sinularolide C, 740.

417

C20H28O6 – Diaporthein B, 460. – Scopararane B, 466. – Flexilarin D, 632. – Uprolide H, 766. – seco-Briarellinone, 820. C20H29BrO2 – Sphaerococcenol A, 954. C20H29ClO3 – Crassocolide H, 565. C20H29ClO4 – Lobocrassin A, 648. C20H29Cl2NO4 – Dichlorolissoclimide, 392. – Haterumaimide E, 399. C20H30Br2O3 – Bromosphaerone, 953. C20H30ClNO4 – Chlorolissoclimide, 391. – Haterumaimide F, 400. C20H30O – Ambliofuran, 351. – 10,15-Cyclo-1,20-epoxy-1,3(20),6,11(18)phytatetraene, 379. – 9(11)-Pargueren-16-al, 490. C20H30O2 – Bifurcane, 353. – Eleganonal, 359. – Styxenol A, 367. – Isocopalendial, 505. – ent-17-Hydroxykaur-15-en-3-one, 541. – Crassarine H, 563. – Deoxosarcophine, 589. – (2R,3E,7S,8S,11E)-2,16:7, 8-Diepoxy-1(15),3, 11-cembratriene, 592. – Isosarcophytoxide, 638. – Knightal, 646. – Lobocrassin F, 653. – Sinularcasbane B, 728. C20H30O3 – Cacofuran B, 390. – Echinohalimane A, 419. – Agallochaol K, 537. – Culobophylin A, 584. – Culobophylin C, 586. – (1R,3R,4S,7E,11E)-(–)-14-Deoxycrassin, 590. – (1S,3S,4R,7E,11E)-(+)-14-Deoxycrassin, 591.

418

Index 2 Compound Molecular Formula Index

– (3E,7S,11Z)-7-Hydroxy-3,11,15-cembratrien20,8-olide, 636. – Lobocrassin B, 649. – Pachycladin D, 919. C20H30O4 – 6-O-(4-Hydroxy-4-methyl-2E-pentenoyl)-6hydroxy-13-nor-1,3-elemadien-11-one, 114. – Scopararane G, 471. – Crassocolide J, 567. – Eunicin, 623. – Flabellatene A, 627. – Jeunicin, 639. – 13αH,14βH-Jeunicin, 640. – (7Z)-Lobocrassolide, 654. – Sinularin, 730. – Sinulariolide, 732. – 11-epi-Sinulariolide, 733. C20H30O5 – 6-O-(4-Hydroxy-4-methyl-2E-pentenoyl)-1,6dihydroxy-13-nor-4,10(14)-germacradien11-one, 119. – 6-O-(4-Hydroxy-4-methyl-2E-pentenoyl)-1,6dihydroxy-13-nor-4(15)-eudesmen-11-one, 158. – 11-Deoxydiaporthein A, 458. – Scopararane F, 470. – Crassocolide K, 568. – 12,13-bisepi-Eupalmerin epoxide, 625. – Flabellatene B, 628. – Flexilarin G, 633. – Pachyclavulariolide I, 682. – Uprolide D, 760. C20H30O6 – Diaporthein A, 459. – Eunicenolide, 622. – Sinulariolone, 735. – Uproeunicin, 748. – Uprolide B, 752. – 8-epi-Uprolide B, 753. – Uprolide C, 756. C20H31BrO4 – Deacetylisoparguerol, 486. C20H31Br2O5S–1 – Tedanol, 472. C20H32 – Isopimara-8(14),15-diene, 462. – Cembrene A, 560. – Yalongene A, 767. – Yalongene B, 768.

C20H32Br2O – Bromosphaerol, 952. C20H32O – (4E,6E,10E)-1,4,6,10,14-Phytapentaen-3-ol, 366. – 4,10-Epoxy-2,7,11-cembratriene, 615. – Sarcophytol A, 717. C20H32O2 – Eleganolone, 358. – 3-Hydroxy-1,4,6,10-phytatetraen-13-one, 362. – Ambliol A, 377. – Ambliol B, 415. – Ambliol C, 416. – Agallochaol Q, 540. – ent-Kaur-15-en-3β,17-diol, 542. – Crassarine F, 562. – 11,12-Epoxy-1,3,7-cembratrien-15-ol, 616. – (+)-11S,12S-Epoxysarcophytol A, 620. – Knightol, 647. – Lobocrassin C, 650. – Lobocrassin E, 652. – Lobophylin B, 661. – Pseudoplexaurol, 690. – Sarcophytol B, 718. – Sinularcasbane E, 729. – Triangulene A, 746. – Triangulene B, 747. – Calyculone A, 771. – Calyculone B, 772. – Calyculone C, 773. – Calyculone H, 774. C20H32O3 – Epoxyeleganolone, 360. – Tagalsin U, 485. – Asperdiol, 550. – Culobophylin B, 585. – Lobophylin A, 660. – Sinugibberol, 727. – Cladiellisin, 827. – Cladieunicellin A, 829. C20H32O4 – Crassumol B, 577. – Dihydrosinularin, 595. – Cladiella peroxide, 825. – Cladieunicellin B, 830. C20H32O5 – Tanyolide B, 82. – Capillolide, 557.

Index 2 Compound Molecular Formula Index

– Sinuflexolide, 726. – Cladieunicellin D, 832. C20H32O6 – Querciformolide D, 695. C20H33BrO2 – Sphaerolabdiene-3,14-diol, 407. C20H33O3 – Agallochaol P, 539. C20H34O – (–)-Nephthenol‡, 679. – Sarcophytol M, 720. – Klysimplexin R, 882. C20H34O2 – (–)-Bifurcadiol, 352. – Bifurcanol, 354. – 5-Hydroxygeranyllinalol, 361. – ent-15,18-Dihydroxylabd-8(17), 13E-diene, 393. – Labdane aldehyde TL95-8673A, 404. – Labdane aldehyde TL95-8673B, 405. – Pavidolide D, 687. – Pavidolide E, 688. – (–)-Sinulariol B, 731. – (−)-Solenopodin C, 939. C20H34O3 – Crassumol A, 576. – Ehrenberoxide B, 612. – Ehrenberoxide C, 613. – Sinulariol Z, 738. – Sarcotol, 785. – Cladieunicellin F, 834. C20H34O4 – Sinulariol J, 734. – Sclerophytin A, 925. C20H34O5 – Dihydrosinuflexolide, 594. C20H35Br2ClO3 – Laurencianol, 381. C20H36O3 – Cacospongionolide C, 355. C20H42O8S2 – 1,18-Phytanediyl disulfate, 365. C20H66O3 – Libertellenone G, 465. C21 C21H22O5 – Pseudopteradiene, 796.

419

C21H22O6 – Pseudopterolide, 799. C21H24O6 – Pukalide, 691. – 11-Gorgiacerol, 793. C21H24O7 – 11,12-Epoxypukalide, 619. C21H24O9 – Diepoxygorgiacerodiol, 792. C21H25BrO5 – Hamigeran F, 334. C21H26O5 – Macfarlandin A, 527. – Macfarlandin B, 528. C21H26O6 – Caulerpenyne, 52. – Ustusolate E, 219. – Caucanolide D, 775. – Caucanolide E, 776. – Caucanolide F, 777. – Caucanolide A, 789. C21H26O7 – Caulerpenynol, 53. – 10,11-Epoxycaulerpenyne, 55. – (6β,9α)-11,12-Epoxy-11-ketone-7-drimene-6O-(5-carboxy-2E,4E-pentadienoyl)-6,9-diol, 207. – 5-epi-Sinuleptolide acetate, 741. – Sinumaximol B, 742. C21H27BrO5 – Hamigeran A ethyl ester, 332. C21H28O4 – Crassumolide C, 580. C21H28O5 – Sarcrassin E, 724. C21H28O6 – Rhipocephalin, 60. C21H28O7 – Caucanolide C, 791. C21H29BrO5 – Hamigeran L methyl ester, 295. C21H30O3 – Echinolabdane A, 394. – Echinoclerodane A, 436. C21H30O4 – Lobophynin C, 662. – Pavidolide A, 684. – Sarcoglaucol, 713.

420

Index 2 Compound Molecular Formula Index

C21H30O5 – Pavidolide C, 686. C21H30O6 – Ehrenbergol C, 610. C21H30O7 – 6β-Acetoxyolepupuane, 197. – 2α,8β,13-Triacetoxycapnell-9(12)-ene-10α-ol, 317. – 3α,8β,14-Triacetoxycapnell-9(12)-ene-10a-ol, 318. C21H30O8 – Gracilin K, 525. C21H31NO4 – 17-Dimethylaminolobohedleolide, 597. C21H32O3 – Cembranoid JNP98-237, 558. C21H32O4 – Ehrenbergol A, 608. – Flexilarin B, 631. C21H32O5 – Durumolide P, 606. – Durumolide Q, 607. C21H34O4 – Ambliolide, 378. C21H35NO2 – Malonganenone C, 363. – Malonganenone H, 364. C21H36O4 – Sclerophytin A methyl ether, 926. C21H36O6 – Sinuflexibilin, 725. C22 C22H24O8 – Lophotoxin, 671. C22H25NO8 – Insulicolide A, 211. C22H26O3 – Capilloquinol, 67. C22H26O5 – 12-Acetoxypseudopterolide, 786. C22H26O6 – Pinnatin B, 780. C22H28O2 – Hydrallmanol A, 50. C22H28O8 – Gracilin H, 522. – Gracilin I, 523. – Sinumaximol C, 743.

C22H29ClO9 – Bis(deacyl)solenolide D, 962. C22H30O4 – (1R,3Z,7E,11E,14S)-18-Acetoxy-3,7,11,15(17)cembratetraen-16,14-olide, 543. – Crassocolide P, 573. – Kericembrenolide A, 641. – Kericembrenolide B, 642. – Lobocrassolide, 655. C22H30O5 – Hamigeran H, 336. – 13-Acetoxysarcocrassolide, 547. – Durumolide B, 602. – (+)-12-Ethoxycarbonyl-11Z-sarcophine, 621. – Kericembrenolide D, 644. – Lobolide, 658. – Michaolide P, 677. – Briarenolide G, 983. C22H30O6 – 18-Acetoxy-3R,4S-epoxy-13R-Hydroxy-7,11,15 (17)-cembratrien-16,14-olide, 545. – 18-Acetoxy-3R,4S-epoxy-13S-Hydroxy-7,11,15 (17)-cembratrien-16,14-olide, 546. – Crassumolide H, 582. – Denticulatolide, 588. – Durumhemiketalolide B, 599. – Durumhemiketalolide C, 600. – Durumolide D, 604. – Michaolide L, 673. – JNP711819-11, 696. – Sarcocrassocolide A, 697. – Sarcocrassocolide B, 698. – Sarcocrassocolide H, 704. – Sarcocrassocolide I, 705. C22H30O7 – Crassocolide L, 569. – Durumolide A, 601. – Sarcocrassocolide F, 702. – Sarcocrassocolide G, 703. – Sarcocrassocolide M, 709. – Sarcocrassocolide N, 710. C22H31Cl2NO5 – Haterumaimide A, 395. C22H32O3 – 19-Acetoxy-13(16),14-Spongiadiene, 493. C22H32O4 – Epoxyphomalin B, 209. – Purpurogemutantidin, 214. – (–)-Cacofuran A, 389.

Index 2 Compound Molecular Formula Index

– 11α-Acetoxy-13-spongien-16-one, 494. – 11β-Acetoxy-13-spongien-16-one, 495. – 13-Acetoxysarcophytoxide, 548. – Astrogorgin N, 807. C22H32O5 – Epoxyphomalin A, 208. – Aplysulphuride, 518. – Chelonaplysin C, 519. – Macfarlandin D, 529. – Norrisolide, 532. – Crassin acetate, 564. – Eupalmerin acetate, 624. – Sarcrassin A, 721. – Briarellin J, 813. – Asbestinin 10, 948. C22H32O6 – 9-Acetoxy-5,8:12,13-diepoxycembr-15(17)- en16,4-olide, 544. – Crassocolide I, 566. – Granosolide A, 634. – Sarcrassin B, 722. – Uprolide A acetate, 750. – 8-epi-Uprolide A acetate, 751. – 7-epi-Uprolide C acetate, 758. – Uprolide D acetate, 761. – 12,13-bisepi-Uprolide D acetate, 762. – Uprolide E acetate, 763. – Briarellin K, 814. – seco-Asbestinin, 949. C22H32O7 – Querciformolide A, 692. – Sinulariolone 3-acetate, 736. – Uprolide B acetate, 754. – 8-epi-Uprolide B acetate, 755. – Uprolide C acetate, 757. – Briarellin K hydroperoxide, 815. C22H33BrO4 – Deoxyparguerol, 487. C22H33BrO5 – Isoparguerol, 488. – Parguerol, 491. C22H33BrO6 – Parguerol 16-acetate, 492. C22H33NO4 – 17-(N,N-Dimethyl)-amino-3,7,11-cembratrien16,2-olid-19-oic acid, 596. C22H34O3 – Lobocrassin D, 651.

– Cladiellin, 826. – 14-Deacetoxycalicophirin B, 841. C22H34O4 – Crassumol C, 578. – Ehrenberoxide A, 611. – 3-Acetylcladiellisin, 801. – Pachycladin C, 918. – Sclerophytin F, 928. – 11-Acetoxy-4-deoxyasbestinin B, 942. – 11-Acetoxy-4-deoxyasbestinin D, 943. C22H34O5 – Cladieunicellin C, 831. C22H34O6 – Tanyolide A, 81. – Alcyonin, 802. C22H34O7 – Querciformolide B, 693. – Briarellin M, 817. C22H36O4 – Acetylehrenberoxide B, 549. – Ehrenbergol B, 609. – Sarcotal acetate, 784. – Klysimplexin T, 887. – (−)-Polyanthelin A, 920. – (+)-Polyanthelin A, 921. – Polyanthellin A, 922. C22H36O5 – Hirsutalin Q, 862. – (–)-6α-Hydroxypolyanthellin A, 864. – Sclerophytin B, 927. – Simplexin S, 938. C22H36O6 – Cladieunicellin E, 833. – Krempfielin L, 895. C23 C23H30O5 – Antibiotic RES-1149-2, 201. C23H32O5 – Sarcocrassocolide E, 701. C23H32O6 – Ustusolate C, 218. – Emblide, 614. – Sarcrassin D, 723. C23H32O7 – 4-O-Acetylverrol, 134. – (E,E)-6-(6ʹ,7ʹ-dihydroxy-2ʹ,4ʹ-octadienoyl)strobilactone A, 204.

421

422

Index 2 Compound Molecular Formula Index

C23H34O4 – Membranolide C, 530. – Membranolide D, 531. C23H34O5 – Ustusolate A, 217. – Gracilin A, 521. C23H34O6 – Palmadorin I, 445. – Palmadorin K, 447. – Gracilin L, 526. C23H36O5 – Palmadorin G, 443. C23H36O6 – Palmadorin E, 441. – Palmadorin J, 446. C23H36O7 – Uprolide G acetate, 765. – Briarellin N, 818. C23H38O4 – Palmadorin A, 437. – Palmadorin D, 440. – Palmadorin M, 449. – Palmadorin N, 450. – 12-Isocopalen-15-oic acid2S,3dihydroxypropyl ester, 508. C23H38O5 – Palmadorin C, 439. – Palmadorin F, 442. – Palmadorin S, 455. – Krempfielin J, 893. C23H39ClO5 – Palmadorin L, 448. C23H39N3O3S – Agelasidine F, 374. C23H40O4 – Austrodorin, 417. C23H40O5 – Palmadorin B, 438. – Palmadorin P, 452. – Palmadorin Q, 453. C23H40O6 – Hirsutalin P, 861. C23H41N3O2S – Agelasidine B, 371. – (+)-Agelasidine C, 372. C23H41N3O3S – Agelasidine E, 373.

C24 C24H26O9 – Bipinnatin D, 553. C24H26O10 – Bipinnatin B, 552. C24H28O10 – (1R,7S,8S,11S,12S,13R)-3,6:11,12-Diepoxy7,13-diacetoxy-8-hydroxy-18-oxo-3,5,15cembratrien-20,10-olide, 593. C24H29ClO8 – Ptilosarcenone, 1119. C24H30O9 – Excavatolide Q, 1030. C24H31ClO8 – Excavatolide A, 1015. – 12-Ptilosarcenol, 1118. C24H31ClO9 – Brianthein X, 980. – Briaviolide A, 997. – Junceellonoid D, 1081. C24H31ClO10 – Brianolide, 976. – Briaviolide D, 1000. – Junceellonoid C, 1080. C24H32N2O6 – Caucanolide B, 790. C24H32O6 – Claviolide, 561. – Kericembrenolide C, 643. C24H32O7 – Crassumolide G, 581. – Lobomichaolide, 659. – Funicolide E, 1055. C24H32O8 – Thuridillin A, 368. – Thuridillin B, 383. – 2,12-Diacetoxy-8,17-epoxy-9-hydroxy-5,13briaradien-18,7-olide, 1007. C24H32O9 – Excavatolide N, 1027. – Minabein 8, 1115. C24H32O10 – Gracilin J, 524. C24H32O11 – Briacavatolide D, 964. C24H34O5 – Udoteal, 369.

Index 2 Compound Molecular Formula Index

– 3,19-diacetoxy-13(16),14-Spongiadiene, 498. C24H34O6 – Purpurogemutantin, 215. – 7α,11α-Diacetoxy-13-spongien-16-one, 499. – 6α,11β-Diacetoxy-13-spongien-16-one, 500. – 7-epi-Funicolide A, 1051. C24H34O7 – 6α,11β-Diacetoxy-14α-hydroxy-12-spongien16-one, 497. – 12-Acetoxytetrahydrosulphurin I, 517. – (1S,3R,4R,6E,8R,12S,13R,14R)-3,4-Epoxy-8,13diacetoxy-6,15(17)-cembradien-16,14-olide, 617. – (1S,3R,4R,6E,8S,12S,13R,14R)-3,4-Epoxy-8,13diacetoxy-6,15(17)-cembradien-16,14-olide, 618. – Granosolide B, 635. – 7-epi-Uprolide C diacetate, 759. C24H34O8 – Chromodorolide A, 520. – Juncenolide N, 1086. C24H34O9 – Briaviolide H, 1004. – Excavatolide E, 1019. C24H34O10 – Briaviolide I, 1005. – Excavatolide M, 1026. C24H35BrO6 – Isoparguerol 16-acetate, 489. C24H36O4 – 3ʹ-Norspongiolactone, 533. – 3,6-Diacetylcladiellisin, 843. C24H36O5 – Flaccidoxide acetate, 629. – Calicophirin B, 824. – Asbestinin 9, 947. C24H36O6 – Astrogorgin B, 804. – Briarellin D, 810. C24H36O7 – Briarellin D hydroperoxide, 811. – Hirsutalin K, 856. – Klymollin D, 866. C24H36O8 – Querciformolide C, 694. – Uprolide F diacetate, 764. C24H38O3 – Litophynin A, 901.

C24H38O4 – Litophynin C, 903. – Litophynin F, 906. – 4-Deoxyasbestinin A, 950. – 4-Deoxyasbestinin C, 951. C24H38O5 – (4β,6α,8Z,13α)-4,12-Diacetoxy-6, 13-epoxy-8-eunicellene, 842. – Litophynin H, 907. – Litophynin J, 910. – Litophynol A, 911. C24H38O6 – Hirsutalin M, 858. – Hirsutalin O, 860. – Klymollin W, 871. – Klymollin X, 872. C24H38O7 – Briarellin O, 819. – Cladieunicellin N, 837. – Cladieunicellin Q, 840. – Hirsutalin N, 859. – Krempfielin M, 896. C24H38O8 – Simplexin R, 937. C24H40O5 – Hirsutalin E, 851. – Litophynin E, 905. C24H40O6 – Litophynin I, 908. – Litophynol B, 912. C24H40O7 – Klysimplexin G, 874. C25 C25H28O11 – Bipinnatin A, 551. C25H32O7 – Anthoptilide C, 957. C25H34O5 – Valdivone A, 940. C25H34O6 – Funicolide A, 1050. C25H34O7 – Briareolate ester I, 986. – Funicolide B, 1052. C25H34O9 – Renillafoulin B, 1121.

423

424

Index 2 Compound Molecular Formula Index

C25H36O5 – Dihydrovaldivone A, 844. C25H37N5O – Asmarine A, 434. – Asmarine B, 435. C25H38O6 – Murrayanolide, 510. C25H40O5 – Verrucosin 4, 370. – Verrucosin 5, 406. – Palmadorin O, 451. – (14αH)-12-Isocopalen-15-oic acid(3-acetoxy-2hydroxypropyl) ester, 506. – 12-Isocopalen-15-oic acid (2-acetoxy-3hydroxypropyl) ester, 507. – Verrucosin 1, 511. – Verrucosin 6, 512. – Verrucosin A, 515. – Verrucosin B, 516. – Verrucosin 3, 534. – Verrucosin 8, 535. – Verrucosin 2, 536. C25H40O6 – Palmadorin H, 444. – Palmadorin R, 454. C25H40O7 – Briarellin P, 821. C25H41ClO5 – Verrucosin 7, 513. – Verrucosin 9, 514. C25H42O5 – 6-Methyl ether of litophynol B, 913. C25H42O6 – Krempfielin B, 889. – Krempfielin N, 897. C26 C26H31ClO10 – Erythrolide A, 1010. C26H32O10 – Michaolide N, 675. C26H33ClO9 – Junceellolide B, 1076. C26H33ClO10 – Junceellolide A, 1075. – Junceellolide C, 1077. C26H33ClO11 – Briaviolide G, 1003. – Fragilide J, 1038.

– Juncin ZI, 1109. C26H34O7 – Anthoptilide B, 956. C26H34O8 – Michaolide Q, 678. – (1S,2S,3E,6S,7E,10S,11E,14S)-6, 10,14-Triacetoxy-3,7,11,15(17)cembratetraen- 16, 2-olide, 745. – Brianthein A, 977. C26H34O9 – Crassolide, 574. – Michaolide M, 674. – Juncenolide K, 1084. C26H34O10 – Brianthein B, 978. – Briareolide D, 994. C26H34O11 – Brialalepolide A, 973. – Brianthein C, 979. C26H34O13 – Juncin Q, 1099. C26H35ClO10 – Briaexcavatolide F, 970. – Stylatulide, 1127. C26H36O6 – Funicolide D, 1054. C26H36O8 – Briareolide K, 996. C26H36O9 – Renillafoulin C, 1122. – Stecholide H, 1126. C26H36O10 – Briaviolide J, 1006. – Junceellolide K, 1079. C26H36O11 – Michaolide O, 676. – Briareolide B, 992. – Excavatolide D, 1018. C26H38O7 – Astrogorgin D, 806. – Briarellin L, 816. – Ophirin, 915. C26H38O8 – Pachyclavulariolide J, 683. – Astrogorgin C, 805. – Calicophirin A, 823. – Labiatin B, 900. – Muricellin, 914.

Index 2 Compound Molecular Formula Index

C26H38O9 – Klymollin C, 865. C26H40N51+ – Agelasine E, 375. – Agelasine F, 376. – Agelasine C, 408. – 5,9-diepi-Agelasine C, 409. – Agelasine J, 410. – Agelasine A, 420. – Agelasine B, 421. – Agelasine D, 422. – Agelasine K, 426. – Agelasine L, 427. C26H40N5O1+ – Agelasine H, 424. – Agelasine I, 425. – Agelasine U, 432. C26H40N5O21+ – Agelasine S, 412. C26H40O7 – Virescenoside C, 475. – 12-epi-Aplysillin, 496. – Cladielloide B, 828. – Hirsutalin D, 850. – Klysimplexin B, 873. – Krempfielin P, 899. C26H40O8 – Virescenoside P, 479. – Cladieunicellin O, 838. C26H40O9 – Virescenoside M, 476. – Cladieunicellin L, 835. C26H42N5O1+ – Agelasine T, 431. C26H42O6 – 6-Acetoxy-litophynin E, 800. – Simplexin A, 929. C26H42O7 – Cryptosphaerolide, 175. – Virescenoside B, 474. – Virescenoside Q, 480. – Hirsutalin H, 853. – Klysimplexin S, 883. – Krempfielin C, 890. – Litophynin I 3-acetate, 909. – Pachycladin B, 917. – Simplexin P, 935. – Simplexin Q, 936.

425

C26H42O8 – Virescenoside A, 473. – Virescenoside O, 478. – Hirsutalin I, 854. – Krempfielin A, 888. – Krempfielin K, 894. C26H42O9 – Virescenoside N, 477. C26H44O7 – Pachycladin A, 916. C27 C27H34O7 – Anthoptilide A, 955. C27H34O9 – Verrucarin A, 140. C27H35ClO10 – Briaviolide B, 998. C27H35ClO11 – Fragilide C, 1035. C27H36O6 – NPR07H239A, 170. – Malayenolide C, 1113. C27H36O7 – 7,18:11,12-Diepoxy-2-(3-methylbutanoyl)-14acetoxy-5,7,11,17-briaratetraen-3-one, 1009. – Malayenolide D, 1114. C27H36O8 – Anthoptilide E, 959. – Funicolide C, 1053. C27H36O11 – Excavatolide Y, 1033. – Stecholide B, 1125. C27H36O13 – Juncin V, 1104. C27H40O8 – Briareolate ester G, 985. – Briareolate ester L, 988. C27H40O9 – Briareolate ester D, 984. C27H40O11 – Klymollin H, 870. C27H42N4O2 – 7-[5-(Decahydro-4a-hydroxy-1,2,5,5tetramethyl-1-naphthalenyl)-3-methyl-2pentenyl]-3,7-dihydro-2,3-dimethyl- 6Hpurin-6-one, 418.

426

Index 2 Compound Molecular Formula Index

C27H42O6 – (11β,16α)-Epoxy-16-acetoxy-,17-O-(3Methylbutanoyl)dihydroxy-15isocopalanal, 501. C27H42O7 – (11β,16α)-Epoxy-12α-hydroxy-16α-acetoxy-17O-(3-methylbutanoyl)-15-isocopalanal, 502. C27H43N5O – (+)-Agelisamine A, 413. C27H44O8 – Krempfielin D, 891. C27H45N5O – (+)-Agelisamine B, 414. C27H46O6S – Klysimplexin sulfoxide A, 884. C28 C28H34O5 – Valdivone B, 941. C28H35ClO12 – 12-epi-Fragilide G, 1037. – Frajunolide C, 1041. – Frajunolide F, 1043. – Frajunolide I, 1044. – Juncenolide M, 1085. – Praelolide, 1117. C28H35ClO13 – Gemmacolide D, 1058. – Juncin P, 1098. C28H36N2O6 – Sarcodictyin A, 923. C28H36O3 – Klysimplexin Q, 881. C28H36O11 – Briaexcavatin C, 967. C28H36O12 – Briaviolide C, 999. – Excavatolide P, 1029. – Tubiporein, 1128. C28H36O13 – Violide B, 1130. C28H36O14 – Juncin W, 1105. C28H37ClO10 – Brianthein Y, 981. – Ptilosarcone, 1120.

C28H37ClO11 – Frajunolide O, 1049. C28H37ClO12 – Frajunolide N, 1048. – Nuiinoalide A, 1116. C28H37ClO13 – Fragilide E, 1036. C28H37NO3 – Haumanamide, 503. C28H38O9 – Chlorodesmin, 356. – 4,9-Diacetoxyudoteal, 357. – Excavatoid E, 1011. C28H38O10 – Briaexcavatolide B, 969. – Briareolide C, 993. C28H38O11 – Excavatolide G, 1021. – Frajunolide A, 1039. – Frajunolide E, 1042. – Frajunolide L, 1046. – Junceellolide D, 1078. – Stecholide A, 1124. C28H38O12 – Excavatoid F, 1012. – Excavatolide C, 1017. C28H38O18 – Frajunolide M, 1047. C28H39ClO10 – Briaviolide F, 1002. C28H40O9 – Astrogorgin, 803. C28H40O10 – Briarenolide F, 982. – Briareolide E, 995. C28H40O11 – Briareolide A, 991. – Excavatolide Z, 1034. C28H40O12 – Briacavatolide E, 965. C28H41ClO9 – Solenolide A, 1123. C28H42O7 – Hirsutalin R, 863. – Litophynin D, 904. C28H42O11 – Klymollin E, 867.

Index 2 Compound Molecular Formula Index

C28H44O5 – Litophynin B, 902. – Asbestinin 8, 946. C28H44O7 – Australin E, 808. – Briarellin S, 822. – Hirsutalin A, 847. – Hirsutalin C, 849. C28H44O8 – Briarellin A, 809. – Hirsutalin F, 852. – Hirsutalin J, 855. – Hirsutalin L, 857. C28H44O9 – Cladieunicellin M, 836. – Cladieunicellin P, 839. – Klysimplexin N, 880. – Krempfielin O, 898. C28H44O10 – Simplexin O, 934. C28H46O6 – Briarellin E, 812. C29 C29H32O7 – Anthoptilide D, 958. C29H32O10 – 2ʹ,3ʹ-Deoxyroritoxin D, 136. C29H34O6 – Malayenolide A, 1111. C29H34O7 – Malayenolide B, 1112. C29H36O5 – Agallochaol O, 538. C29H38N2O6 – Sarcodictyin B, 924. C29H38O7 – 12,13-Deoxyroridin E, 135. C29H38O9 – 12‘-Hydroxyroridin E, 137. – Roridin R, 139. C29H38O13 – Gemmacolide N, 1064. – Juncenolide O, 1087. C29H39ClO11 – Briaviolide E, 1001. C29H40O11 – Excavatolide W, 1032. – Frajunolide J, 1045.

C29H46O7 – Pachyclavulariolide F, 681. C30 C30H34O3 – Anthogorgiene G, 222. C30H37ClO14 – Dichotellide T, 1008. – Gemmacolide G, 1059. – Juncin E, 1096. C30H37ClO15 – Gemmacolide O, 1065. C30H38O13 – Excavatolide O, 1028. C30H39ClO14 – Gemmacolide V, 1072. C30H40O11 – Excavatolide F, 1020. C30H40O13 – Frajunolide B, 1040. – Juncin Y, 1107. C30H40O14 – Juncin X, 1106. C30H42O11 – Brialalepolide B, 974. – Junceol E, 1092. – Junceol H, 1095. C30H42O12 – Excavatolide B, 1016. C30H42O13 – Briacavatolide C, 963. – Briacavatolide F, 966. – Briaexcavatolide P, 972. – Excavatoid O, 1013. C30H43ClO14 – Excavatoid P, 1014. C30H44O13 – Briaexcavatolide L, 971. – Excavatolide K, 1025. C30H46O5 – Disydonol A, 97. – Disydonol C, 98. C30H46O9 – Hirsutalin B, 848. C30H48O6 – Asbestinin 6, 944. C30H48O7 – Asbestinin 7, 945. C30H48O8

427

428

Index 2 Compound Molecular Formula Index

– Calyculaglycoside A, 554. – Calyculaglycoside B, 555. – Calyculaglycoside C, 556. – Krempfielin I, 892. C30H48O9 – Klysimplexin H, 875. – Klysimplexin L, 878. – Simplexin M, 932. C30H48O10 – Klysimplexin M, 879. – Simplexin N, 933. C30H48O10S – Klysimplexin sulfoxide C, 886. C31 C31H32O2 – Gorgiabisazulene, 233. C31H37ClO9 – Benzyl briaviolide A, 961. C31H40BrN6O31+ – Agelasine P, 428. – Agelasine Q, 429. – Agelasine R, 430. C31H40O15 – Juncenolide D, 1082. C31H41ClO12 – Gemmacolide I, 1060. C31H42BrN6O21+ – Agelasine O, 411. – Agelasine G, 423. C31H43ClO12 – Juncenolide J, 1083. C31H43ClO14 – Juncin R, 1100. – Juncin S, 1101. C31H43N6O21+ – Ageline B, 433. C31H44O11 – Junceol A, 1088. – Junceol F, 1093. – Junceol G, 1094. C31H52O9S – Klysimplexin sulfoxide B, 885. C32 C32H42O13 – Excavatolide V, 1031. C32H44O13 – Excavatolide I, 1023.

– Excavatolide J, 1024. C32H45ClO13 – Juncin ZII, 1110. C32H46O11 – Brialalepolide C, 975. C32H46O12 – Violide A, 1129. – Violide N, 1131. C33 C33H39ClO12 – 12-O-Benzoyl-12-O-deacetylpteroidine, 960. C33H43ClO14 – Gemmacolide J, 1061. – Gemmacolide Y, 1074. – Juncin O, 1097. C33H43ClO15 – Gemmacolide K, 1062. C33H44O15 – Gemmacolide P, 1066. C33H44O16 – Gemmacolide Q, 1067. – Gemmacolide R, 1068. C33H45ClO14 – Gemmacolide B, 1056. – (+)-Gemmacolide B, 1057. – Gemmacolide T, 1070. – Gemmacolide U, 1071. C33H46O13 – Briaexcavatin E, 968. C33H50O9 – Briareolate ester M, 989. – Briareolate ester N, 990. C33H50O10 – Briareolate ester K, 987. C33H52O11 – Simplexin E, 931. C34 C34H46O14 – Juncin U, 1103. C34H46O15 – Gemmacolide M, 1063. C34H47ClO14 – Juncin Z2, 1108. C34H48O13 – Excavatolide H, 1022. C34H56O11 – Simplexin D, 930.

Index 2 Compound Molecular Formula Index

C35 C35H46O11 – Roridin Q, 138. C35H48N2O10 – Eleutherobin, 845. C35H49ClO14 – Junceol B, 1089. C35H50O13 – Junceol D, 1091. C36 C36H48N2O11 – Eleuthoside A, 846. C36H48O17 – Juncin T, 1102. C38 C38H53ClO16 – Gemmacolide W, 1073. C38H55ClO14 – Junceol C, 1090. C38H63BrO6 – 2-Acetoxy-15-bromo-7,16-dihydroxy-3palmitoyl-neoparguera-4(19),9(11)-diene, 481. C40 C40H62O8S – Thioflexibilolide A, 744. C41 C41H62O8 – Lobophytone Z, 669. – Methyl sartortuoate, 672. – Petronigrione, 689.

C41H64O8 – Lobophytone X, 667. C41H64O9 – Lobophytone U, 664. C41H64O10 – Lobophytone V, 665. C41H68O11 – Klymollin F, 868. C42 C42H47NO12 – Bis(pseudopterane)amine, 788. C42H57NO3 – Popolohuanone F, 456. C42H74O8 – Klysimplexin J, 876. C43 C43H60O18 – Gemmacolide S, 1069. C43H66O8 – Lobophytone Y, 668. C43H66O10 – Nyalolide, 680. C43H68O9 – Lobophytone W, 666. – Lobophytone Z1, 670. C43H72O11 – Klymollin G, 869. C44 C44H78O8 – Klysimplexin K, 877.

429

Index 3 Compound Organism Source Index This index lists in alphabetical order all 439 marine organism in Latin names in HAMNP Volume 1, following a code sequence of related active compounds. When one hopes to know the English type name of any marine organism, please see an entry of a related compound in the code sequence. For example, if one hopes to know the English common type name of “Acanthella montereyensis” (just in the second line of this index), from entry 506 or 507, one will know that the Acanthella montereyensis is a sponge. A Acalycigorgia sp. 233. Acanthella montereyensis 506, 507. Acremonium neo-caledoniae 134, 140. Acremonium striatisporum KMM 4401 473, 474, 475, 476, 477, 478, 479, 480. Agelas cf. mauritiana 410, 426, 427. Agelas citrina 373, 374. Agelas dispar 372. Agelas mauritiana 409, 413, 414, 418, 424, 425. Agelas nakamurai 371, 372, 375, 376, 408, 420, 421, 422, 433. Agelas sp. 375, 376, 376, 376, 408, 411, 412, 420, 421, 422, 422, 423, 428, 429, 430, 431, 432, 433, 433. Ainigmaptilon antarcticus 141. Alcyonium flaccidum 718. Alcyonium paessleri 246, 247, 248, 249, 342, 343. Alcyonium sp. 225. Alcyonium valdivae 844, 940, 941. Amphiroa nidifica 133. Anthogorgia sp. 222. Anthopleura pacifica 121. Anthoptilum cf. kukenthali 955, 956, 957, 958, 959. Apiospora montagnei 482, 482. Aplysia angasi 77. Aplysia brasiliana 142, 145. Aplysia californica 20, 22, 23, 260. Aplysia dactylomela 15, 37, 46, 87, 88, 96, 124, 125, 128, 129, 130, 131, 261, 263, 265, 266, 267, 268, 273, 274, 328, 487, 488, 489, 491, 492. Aplysia kurodai 9, 10, 11, 12, 36, 171, 177, 178, 179, 180, 181. Aplysia punctata 5, 6, 7, 39, 46. Aplysia sp. 133. Aplysia spp. 129.

Aplysilla sp. 517. Aplysilla tango 521. Archidoris montereyensis 206, 507, 508. Archidoris odhneri 54. Archidoris pseudoargus 506, 507. Archidoris tuberculata 506, 507. Arthrinium sacchari 464. Arthrinium sp. 482. Ascidia mentula 365, 388. Ascobulla fragilis 57. Aspergillus insuetus OY-207 204, 216. Aspergillus insulicola 211. Aspergillus sp. 76, 86, 97, 98, 99, 100, 101, 110, 111, 112, 113. Aspergillus terreus 324, 326, 327. Aspergillus ustus 201, 201, 204, 207, 217, 218, 219, 219, 219. Aspergillus versicolor 198, 211. Astrogorgia sp. 803, 804, 805, 806, 807, 823, 824, 841, 914, 915. Austrodoris kerguelenensis 417, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455. Axinella sp. 237. Axinyssa fenestratus 191. Axinyssa sp. 224. B Bathydoris hodgsoni 210. Bifurcaria bifurcata 352, 353, 354, 358, 359, 360. Briareum asbestinum 809, 810, 812, 820, 822, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 981, 984, 985, 986, 987, 988, 989, 990, 996. Briareum excavatum 963, 964, 965, 966, 967, 968, 969, 970, 971, 972, 977, 978, 979, 1007, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, 1019, 1020, 1021, 1022, 1023, 1024, 1025, 1026, 1027,

Index 3 Compound Organism Source Index

1028, 1029, 1030, 1031, 1032, 1033, 1034. Briareum polyanthes 810, 811, 813, 814, 815, 816, 817, 818, 819, 821, 920, 922, 980, 981. Briareum sp. 973, 974, 975, 976, 982, 983, 991, 992, 993, 994, 995, 1128, 1129, 1130, 1131. Briareum sp. DD6 1007. Briareum stechei 976. Briareum violacea 961, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006, 1015, 1123. Bruguiera gymnorrhiza 201, 217, 218, 219. C Cacospongia mycofijiensis 289, 290. Cacospongia sp. 389, 390. Cadlina luteomarginata 68, 199, 199, 200, 518. Cadophora malorum 190, 193. Calicogorgia sp. 823, 824, 915. Capnella imbricata 310, 311, 312, 313, 314, 315. Caulerpa bikiniensis 79. Caulerpa flexilis 56. Caulerpa prolifera 52. Caulerpa taxifolia 52, 53, 55, 57. Cerbera manghas 47. Ceriops tagal 483, 484, 485. Cespitularia sp. 118, 153, 234. Chelonaplysilla spp. 379, 519. Chelonaplysilla violacea 532. Chlorodesmis fastigiata 356. Chondria oppositiclada 159. Chondrococcus hornemanni 19, 25. Chondrostereum sp. 319, 322. Chromodoris capensis 304. Chromodoris cavae 520. Chromodoris geminus 496. Chromodoris luteorosea 496, 527. Chromodoris macfarlandi 527, 528, 529. Chromodoris maridadilus 304. Chromodoris maridadulis 303. Chromodoris norrisi 532. Cladiella australis 801, 827, 927. Cladiella hirsuta 847, 848, 849, 850, 851, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 905.

431

Cladiella kashmani 629. Cladiella krempfi 800, 801, 864, 888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898, 899, 905, 906, 909, 912, 913, 925, 926, 927, 928. Cladiella pachyclados 801, 826, 843, 874, 916, 917, 918, 919, 921, 925, 926. Cladiella shaeroides 825. Cladiella similis 827. Cladiella sp. 808, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 890, 895, 938, 939. Cladiella sphaeroides 827. Cladiella spp. 826. Clavularia koellikeri 234, 235, 236, 641, 642, 643, 644, 645, 745. Clavularia violacea 561. Clavularia viridis 238, 349. Cliona caribboea 49. Codium fragile 198. Corallina chilensis 133. Corallina pilulifera 133. Cryptosphaeria eunomia var. eunomia 458. Cryptosphaeria sp. 175. Curvularia lunata 76. Cyerce nigricans 356. Cymbastela hooperi 194. Cystophora moniliformis 384. Cystoseira balearica 358, 359, 360. D Darwinella oxeata 518. Dasystenella acanthina 154. Dendrilla membranosa 530, 531. Dendrilla sp. 532. Dendrilla spp. 379. Dendrobeania murrayana 510. Dendrodoris carbunculosa 203. Dendrodoris grandiflora 197, 202. Dendrodoris krebsii 213. Dendrodoris limbata 202, 213. Dendrodoris nigra 213. Dendrodoris tuberculosa 213. Dendronephthya rubeola 310, 311, 313, 314, 315, 316, 317, 318, 329. Diacarnus cf. spinopoculum 382, 457. Diacarnus erythraenus 231. Dichotella gemmacea 101, 111, 113, 1008, 1059, 1060, 1061, 1062, 1063, 1064, 1065, 1066,

432

Index 3 Compound Organism Source Index

1067, 1068, 1069, 1070, 1071, 1072, 1073, 1074, 1082, 1083, 1097, 1100, 1101, 1103, 1117. Dictyodendrilla sp. 69, 70, 71. Didemnum molle 163, 166. Didiscus flavus 93. Doris verrucosa 370, 406, 511, 512, 513, 514, 515, 516, 534, 535, 536. Drechslera dematioidea 280, 281. Dysidea amblia 351, 377, 378, 415, 416. Dysidea arenaria 78. Dysidea cf. arenaria 494, 495, 497, 499, 500, 501, 502. Dysidea fragilis 292, 303, 304. Dysidea herbacea 250, 296. Dysidea sp. 75, 196, 202, 205, 212, 213, 220, 221, 250, 300, 301, 456. Dysidea spp. 379, 532. E Echinogorgia complexa 223, 227. Echinomuricea sp. 394, 419, 436. Ectyoplasia ferox 208, 208, 209, 209. Efflatounaria sp. 118. Eleutherobia aurea 846, 923. Eleutherobia cf. albiflora 845. Eleutherobia sp. 1115. Ellisella robusta 1037, 1077. Elysia sp. 356. Enteromorpha sp. 190, 193. Epipolasis sp. 95. Erythropodium caribaeorum 845, 1010. Eunicea asperula 550. Eunicea calyculata 771, 772, 773. Eunicea fusca 115. Eunicea knighti 646, 647. Eunicea mammosa 617, 618, 623, 624, 639, 640, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 763, 764, 765. Eunicea palmari 624. Eunicea pinta 626, 766. Eunicea sp. 114, 116, 119, 120, 152, 158, 554, 555, 556, 774. Eunicea succinea 622, 623, 624, 625, 639, 748, 749, 762. Eunicea tourneforti 550, 636. Eunicella cavolini 842. Eunicella labiata 900.

Eupentacta fraudatrix 473, 474, 475, 476, 477, 478, 479, 480. Euplexaura erecta 225. Euplexaura nuttingi 363, 364. Euplotes crassus 59, 83. Euplotes raikovi 58, 305. Euplotes rariseta NZ2 293. Euplotes rariseta PBH1, BR1 and GRH5 306, 307. Eutypella scoparia 458, 459, 460, 462, 463, 466, 467, 468, 469, 470, 471. Eutypella sp. D-1 465. Excoecaria agallocha 393, 537, 538, 539, 540, 541, 542. F Fasciospongia cavernosa 355. Fasciospongia sp. 302. Flustra foliacea 1, 2. Funiculina quadrangularis 1050, 1051, 1052, 1053, 1054, 1055. G Gelidium sesquipedale 36. Geodia cydonium 482. Gorgonella umbraculum 1117. H Haliclona sp. 320, 321. Halimeda opuntia 357. Halimeda spp. 357. Hamigera tarangaensis 294, 295, 330, 330, 331, 331, 332, 332, 333, 333, 334, 335, 336, 337, 338, 339, 340, 341. Haminoea cymbalum 84. Heterogorgia uatumani 160. Heteroxenia sp. 189. Hydrallmania falcata 50. Hypselodoris californiensis 303. Hypselodoris cantabrica 75. Hypselodoris capensis 303. Hypselodoris ghiselini 303. Hypselodoris ghisleni 304. Hypselodoris godeffoyana 304. Hypselodoris godeffroyana 303. Hypselodoris tricolor 75. Hypselodoris villafranca 75. Hypselodoris webbi 251.

Index 3 Compound Organism Source Index

I Ircinia selaginea 380. Isis hippuris 298, 323, 344, 345, 346, 347, 348. J Jackiella javanica 115. Junceella fragilis 1035, 1036, 1038, 1039, 1040, 1041, 1042, 1043, 1044, 1045, 1046, 1047, 1048, 1049, 1075, 1075, 1075, 1076, 1076, 1076, 1077, 1077, 1078, 1078, 1078, 1079, 1080, 1081, 1081, 1085, 1087, 1107, 1109, 1117. Junceella gemmacea 1056, 1058. Junceella juncea 1056, 1056, 1057, 1077, 1083, 1084, 1085, 1086, 1087, 1087, 1088, 1089, 1090, 1091, 1092, 1093, 1094, 1095, 1096, 1097, 1098, 1099, 1100, 1101, 1102, 1103, 1104, 1105, 1106, 1107, 1108, 1109, 1110. K Kandelia candel 147, 148, 149, 150, 151. Klyxum molle 837, 865, 866, 867, 868, 869, 870, 871, 872, 925, 927. Klyxum simplex 873, 874, 875, 876, 877, 878, 879, 880, 881, 882, 883, 884, 885, 886, 887, 929, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938. L Laurencia caespitosa 87, 88. Laurencia cartilaginea 257, 266, 271. Laurencia chondrioides 262, 266. Laurencia claviformis 260, 274. Laurencia composita 270. Laurencia elata 260, 266. Laurencia intermedia 132, 133. Laurencia johnstonii 132. Laurencia majuscula 256, 260, 262, 263, 274. Laurencia marianensis 260, 274. Laurencia nidifica 133, 264, 265, 274. Laurencia nipponica 159, 260. Laurencia obtusa 127, 267, 273, 291, 297, 299, 381, 481, 486. Laurencia okamurai 132, 133, 255, 258. Laurencia pacifica 274. Laurencia pannosa 287, 288.

433

Laurencia pinnatifida 258. Laurencia poitei 328. Laurencia rigida 85, 252, 253, 254, 259, 266. Laurencia saitoi 490. Laurencia scoparia 266, 269. Laurencia sp. 124, 126, 127, 258, 272. Laurencia spp. 129. Lemnalia africana 182, 309. Lemnalia cervicorni 350. Lemnalia laevis 182. Lemnalia tenuis 350. Leptogorgia gilchristi 363. Leptogorgia laxa 671. Leptogorgia setacea 619. Leptogorgia virgulata 691. Liagora viscida 280, 281. Libertella sp. 463, 464. Lissoclinum sp. 395, 396, 397, 398, 399, 400, 401, 402, 403. Lissoclinum voeltzkowi 391, 392. Lissodendoryx flabellate 627, 628. Litophyton sp. 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911, 912. Litophyton viridis 679. Lobiger serradifalci 57. Lobophytum crassum 543, 545, 546, 548, 558, 573, 574, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 589, 601, 602, 603, 648, 649, 650, 651, 652, 653, 655, 656, 657, 658, 660, 661, 663, 690, 696, 739, 740. Lobophytum cristagalli 663. Lobophytum denticulatum 588. Lobophytum durum 543, 545, 546, 579, 580, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 739, 740. Lobophytum hedleyi 656, 657. Lobophytum michaelae 574, 659, 673, 674, 675, 676, 677, 678. Lobophytum pauciflorum 592, 664, 665, 666, 667, 668, 669, 670, 672, 680. Lobophytum schoedei 662. Lobophytum sp. 559, 596, 597, 620, 654, 657, 660, 661, 715. Lophogorgia alba 671, 691. Lophogorgia chilensis 691. Lophogorgia cuspidata 671, 691. Lophogorgia rigida 671, 691. Lophogorgia violacea 593.

434

Index 3 Compound Organism Source Index

M Marginisporum aberrans 133. Menella praelonga 1117. Menella sp. 117, 229. Microcladia spp. 40. Microsphaeropsis sp. 176. Minabea sp. 1115. Muricella sp. 803, 823, 824, 841, 914. Muricella spp. 915. Mycale sp. 457. Myrmekioderma dendyi 94, 95. Myrmekioderma sp. 102, 103. Myrmekioderma styx 361, 362, 366, 367. Myrothecium roridum 135. Myrothecium roridum TUF 98F42 136, 137, 138. Myrothecium sp. TUF 98F2 139. Myxilla incrustans 176. N Neomeris annulata 143, 144. Nephthea chabroli 122, 845. Nephthea chabrolii 226, 230. Nephthea erecta 282. Nephthea sp. 183. Nephthea spp. 679. Nerita albicilla 48. Niphates olemda 76. O Occurs in algae 211. Occurs in corals 560. Occurs in essential oils 1. Occurs in higher plants 560. Oceanapia bartschi 377. Ochtodes crockeri 28, 29, 30, 31, 32, 33. Ochtodes secundiramea 34. Oligoceras hemorrhages 68. Onchidella binneyi 80. Oxynoe olivacea 57. P Pachyclavularia violacea 681, 682, 683, 1129, 1130. Pacifigorgia cf. adamsii 286. Pacifigorgia media 118. Pacifigorgia pulchraexilis 118. Pantoneura plocamioides 20. Paraconiothyrium cf. sporulosum 208, 209. Parahigginsia sp. 104, 105, 106, 107, 108, 109.

Paralemnalia thyrsoides 182, 182, 183, 184, 185, 186, 187, 188. Paramuricea chamaeleon 228. Penicillium purpurogenum 214, 215. Penicillium sp. 163, 166. Penicillium sp. BL27-2 162. Penicillium sp. PR19 N-1 164, 165, 167, 168, 169. Penicillus capitatus 211. Periconia byssoides 171, 177, 178, 179, 180, 181. Periconia byssoides OUPS-N133 172, 173, 174, 283. Petrosia nigricans 689. Phoma sp. 208, 209. Phyllidia pustulosa 191. Planaxis sulcatus 595, 639, 733. Pleurobranchaea meckelii 404, 405. Plexaurella grisea 51, 63, 64, 65, 66. Plexauroides praelonga 1117. Plocamium angustum 3, 4. Plocamium cartilagineum 8, 15, 20, 22, 26, 37, 38, 41, 42, 43, 44, 45, 46. Plocamium cruciferum 26. Plocamium hamatum 36, 37, 39, 41, 43. Plocamium mertensii 39, 41. Plocamium oregonum 20. Plocamium spp. 20, 21, 23. Plocamium violaceum 40, 41, 42. Polysiphonia violacea 482. Portieria hornemanni 13, 16, 19, 25, 27, 35. Portieria hornemannii 14, 17, 18, 24, 34. Preissia quadrata 115. Psammaplysilla purpurea 962. Psammocinia sp. 204, 216. Pseudoplexaura porosa 564, 591, 690. Pseudoplexaura sp. 623. pseudoplexaura spp. 564. Pseudopterogorgia acerosa 90, 788, 792, 793, 796, 797, 798, 799. Pseudopterogorgia americana 90, 115, 232. Pseudopterogorgia bipinnata 551, 552, 553, 775, 776, 777, 779, 780, 781, 782, 783, 787, 789, 790, 791, 794. Pseudopterogorgia elisabethae 786. Pseudopterogorgia kallos 794, 795. Pseudopterogorgia rigida 89, 90, 91, 92, 93, 94. Pseudopterogorgia sp. 118.

Index 3 Compound Organism Source Index

Pteroeides laboutei 960. Ptilosarcus gurneyi 1118, 1119, 1120. R Raspailia spp. 434. Renilla reniformis 1115, 1121, 1122. Rhipocephalus phoenix 60, 61. Rhodomela californica 133. Ritterella rete 73. Rumphella antipathies 123. S Sarcodictyon roseum 923, 924. Sarcophyton acutangulum 238, 349. Sarcophyton crassocaule 547, 565, 566, 567, 568, 569, 570, 575, 588, 626, 697, 698, 699, 700, 701, 712, 721, 722, 723, 724. Sarcophyton crassocaule 20070402 709, 710, 711. Sarcophyton decaryi 716. Sarcophyton ehrenbergi 549, 608, 609, 610, 611, 612, 613, 621. Sarcophyton glaucum 589, 614, 680, 713, 715, 718, 719, 720. Sarcophyton infundibuliforme 714. Sarcophyton molle 637, 716. Sarcophyton sp. 578, 592, 615, 638, 717, 784, 785. Sarcophyton spp. 589. Sarcophyton tortuosum 319, 672. Sarcophyton trocheliophorum 589, 767, 768. Sargassum sp. 385, 386, 387. Sclerodoris tanya 81, 82. Sclerophytum capitalis 925, 927, 928. Scytalium tentaculatum 1009. Sea hare 174. Sidnyum turbinatum 365, 388. Sinularia abrupta 691. Sinularia capillosa 67, 72, 544, 557, 730, 732. Sinularia crassa 562, 563. Sinularia crassocaule 571, 572, 573, 702, 703, 704, 705, 706, 707, 708. Sinularia erecta 308, 691. Sinularia flexibilis 560, 587, 594, 595, 630, 631, 632, 633, 725, 726, 730, 732, 733, 735, 736, 744, 802. Sinularia gibberosa 616, 715, 727, 739, 740. Sinularia granosa 634, 635, 693, 694.

435

Sinularia gyrosa 769, 770. Sinularia inelegans 778. Sinularia kavarattiensis 243. Sinularia leptoclados 308. Sinularia lochmodes 239, 240, 241, 242. Sinularia maxima 742, 743. Sinularia mayi 115, 588, 731. Sinularia microclavata 557. Sinularia notanda 693. Sinularia pavida 684, 685, 686, 687, 688. Sinularia polydactyla 308, 671, 691. Sinularia querciformis 692, 693, 694, 695, 735, 736. Sinularia rigida 734, 737, 738. Sinularia scabra 192. Sinularia sp. 62, 74, 244, 245, 557, 616, 717, 718, 728, 729, 730, 741. Sinularia spp. 72. Sinularia tenella 557. Sinularia triangula 590, 595, 730, 746, 747. Smenospongia sp. 574. Solenopodium sp. 1123. Solenopodium stechei 1124, 1125, 1126. Sonneratia apetala 275, 276, 277, 278, 279. Sphaerococcus coronopifolius 407, 952, 953, 954. Spirastrella inconstans 284, 285. Spongia matamata 504. Spongia officinalis 505. Spongia sp. 493, 498, 503. Spongia spp. 509. Spongionella gracilis 521. Spongionella sp. 518, 521, 522, 523, 524, 525, 526, 533. Streptomyces sp. 147, 148, 149, 150, 151. Stylatula sp. 1127. Subergorgia suberosa 323, 325. Suberites domuncula 201, 204, 207, 219, 219. T Talaromyces flavus 275, 276, 277, 278, 279. Tedania ignis 472. Terrestrial ant Dendrolasius fuliginosus 68. Terrestrial fungus Acremonium luzulae 473, 475. Terrestrial fungus edible mushroom Strobilurus ohshimae 216. Terrestrial fungus Oospora virescens 474. Terrestrial fungus Sclerotinia fruticula 193.

436

Index 3 Compound Organism Source Index

Terrestrial plants Plumeria spp. 49. Terrestrial plants Polygonum hydropiper and Drimys lanceolata 213. Thespesia populnea 195. Thuridilla hopei 368, 383. Tochuina tetraquetra 691. Tubipora musica 155, 156, 157, 161. Tubipora sp. 1128.

Unidentified octocoral 1116. Unidentified soft coral 322. Unidentified sponge 139, 464, 520.

U Udotea argentea 369. Udotea flabellum 369. Unidentified alga 76. Unidentified ascidian 175, 461. Unidentified marine-derived fungus 320, 321.

X Xestospongia testudinaria 86, 97, 98, 99, 100, 110, 112. Xylaria sp. 170. Xylocarpus granatum 275.

V Veretillum malayense 1111, 1112, 1113, 1114. Verrucosispora gifhornensis 461. Virgularia juncea 146, 827.

Index 4 Compound Sampling Geographic Locality Index In this index, all geographic locations in HAMNP Volume 1 have been devided as 15 large areas: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

CHINA JAPAN KOREA WATERS ASIA AUSTRALIA OCEANIA EUROPE AFRICA USA NORTH AMERICA CARIBBEAN SEA SOUTH AMERICA PACIFIC OCEAN ATLANTIC OCEAN ANTARCTIC/ARCTIC

For all 148 compound sampling geographic locations, each of them has put into one large area, and then within the area, all related geographic places are listed in alphabetical order with the detail information in the texts of the “Handbook of Active Marine Natural Products” books and a number code sequence of the related compounds follows the detail information immediately. There are 843 related compounds with geographic information in HAMNP Volume 1. 1 CHINA China, Beibuwan Bay, Guangxi 803, 804, 805, 806, 807, 823, 824, 841, 914, 915, 1008, 1070, 1071, 1072, 1073, 1074, 1083, 1117. China, Bohai Bay, Tianjin 214, 215. China, China waters 101, 111, 113, 201, 217. China, Dalian, Liaoning 198. China, Dongluo I., Hainan 62, 74, 244, 245, 557, 730. China, Dongsha Atoll, South China Sea 67, 548, 576, 577, 578, 578, 581, 582, 583, 606, 607, 611, 612, 613, 630, 660, 661, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 769, 770, 873, 874, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938. China, Guangxi 380, 393, 537, 538, 539, 540, 541, 542. China, Hainan 275, 276, 277, 278, 279, 319, 483, 484, 485, 664, 665, 666, 667, 668, 669, 670, 672, 680.

China, Meishan I., Hainan 1008. China, Pingtan I., Fujian 270. China, Rongcheng 255. China, Sanya Bay, Hainan 684, 685, 686, 687, 688, 734, 737, 738. China, Sanya, Hainan 1110. China, Weizhou coral reef, Guangxi 86, 99, 100, 110, 112, 714. China, Weizhou I., Guangxi 97, 98, 222. China, Wenchang, Hainan 218, 219. China, Xiamen, Fujian 147, 148, 149, 150, 151. China, Ximao I., Hainan, South China Sea 728, 729. China, Yalong Bay, Hainan 767, 768. South China Sea, South China Sea 458, 459, 460, 462, 463, 466, 467, 468, 469, 470, 471, 1037, 1056, 1059, 1060, 1061, 1062, 1063, 1064, 1065, 1066, 1067, 1068, 1069, 1075, 1076, 1077, 1078, 1080, 1081, 1082, 1097, 1098, 1099,

438

Index 4 Compound Sampling Geographic Locality Index

1100, 1101, 1102, 1103, 1104, 1105, 1107, 1108, 1109. Taiwan, along coast of Penghu Is. 871, 872, 925, 927. Taiwan, Green I. 182, 183, 185, 186, 187, 188, 282. Taiwan, Kenting 569, 571, 572, 573. Taiwan, Northeast Taiwan 648, 649, 650, 651, 652, 653, 690. Taiwan, northern coast of Taiwan 239, 240, 241, 242. Taiwan, off coast of Penghu is. 800, 801, 892, 893, 894, 895, 896, 897, 898, 899, 906, 909, 912, 913, 925, 927, 928. Taiwan, off coast of Sianglu Islet, Penghu Is. 851, 859, 860, 861, 862, 863, 905. Taiwan, off coast of Southern Taiwan 967, 968. Taiwan, Orchid I. 963, 964, 965, 966. Taiwan, Penghu Is. 865, 866, 867, 868, 869, 870, 888, 889, 890, 891, 905. Taiwan, Pingtung County 584, 585, 586, 659, 660, 661, 673, 674, 675, 676, 677, 678, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006, 1015, 1123. Taiwan, Sansiantai, Taitung County 549, 562, 563, 610. Taiwan, Sianglu Islet, Penghu Is. 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858. Taiwan, Siaoliouciou I. 122. Taiwan, South Bay, Kenting, Southernmost tip 971, 1007. Taiwan, Southern coast of Taiwan 229, 587, 631, 632, 633. Taiwan, Southern Taiwan 117, 192. Taiwan, Taitung County 184, 590, 595, 608, 609, 621, 730, 741, 744, 746, 747, 1046, 1047, 1048, 1049, 1085, 1085, 1086, 1087. Taiwan, Taiwan waters 104, 105, 106, 107, 108, 109, 156, 157, 161, 394, 419, 436, 547, 561, 565, 566, 567, 568, 570, 574, 575, 594, 655, 712, 725, 726, 727, 778, 835, 836, 838, 839, 840, 890, 895, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, 1019, 1020, 1021, 1022, 1023, 1024, 1025, 1026, 1031, 1032, 1033, 1034, 1035, 1036, 1037, 1038, 1039, 1040, 1041, 1042, 1043, 1044, 1045,

1075, 1076, 1077, 1078, 1079, 1081, 1084, 1087, 1088, 1089, 1090, 1091, 1092, 1093, 1094, 1095, 1107, 1109. 2 JAPAN Japan, Atami-shi, Shizuoka 464. Japan, Hiroshima 461. Japan, Japan waters 155, 163, 166, 180, 181, 233, 238, 238, 349, 349, 385, 386, 387, 662, 731, 784, 785, 825, 911, 1131. Okinawa, Okinawa 256, 371, 372, 375, 376, 389, 390, 395, 396, 397, 398, 399, 400, 401, 402, 403, 408, 411, 412, 420, 421, 422, 423, 428, 429, 430, 431, 432, 433, 494, 495, 497, 500, 501, 502, 641, 642, 643, 644, 645, 745. 3 KOREA WATERS Korea waters, 823, 841, 914. 4 ASIA Bering Sea 162. India waters 292. India Kavaratti I., Lakshadweep Is. 864. India Southern India 308. Indian Ocean 1057. Indian Ocean Andaman and Nicobar Is. 827, 927. Indian Ocean, Tuticorin coast 1056. Indonesia 76, 139, 226, 230, 311, 314, 422, 574, 828, 829, 830, 831, 832, 833, 834, 938, 939, 1111, 1112, 1113, 1114. Indo-Pacific Sea Indo-Pacific 320. Israel Sdot-Yam 204, 216. Malaysia 287, 288. Malaysia N. Borneo I., Sabah 124, 258. Philippines Baler, Aurora 376. Philippines 189, 272, 596, 735. Philippines West Angaur 521, 522, 523, 524, 525, 526, 533. Red Sea 231, 801, 826, 843, 874, 916, 917, 918, 919, 921, 925, 926. Saudi Arabia Jiddah 291, 297, 299. Sea of Japan 476. Thailand 78, 615. Thailand Phi-Phi I., Krabi province 102, 103. Vietnam 559, 654. Vietnam Haivan, Danang 689. Vietnam Nha trang Bay 742, 743.

Index 4 Compound Sampling Geographic Locality Index

5 AUSTRALIA Australia 3, 4, 46, 69, 70, 71, 85, 252, 253, 254, 520, 620, 955, 956, 957, 958, 959. Australia Great Australian Bight 237. Great Barrier Reef, Australia Bowden Reef 616, 718. Great Barrier Reef, 37, 92, 260, 300, 301, 558, 1124, 1125, 1126. Great Barrier Reef, Australia Kelso Reef 194. Queensland Townsville area 182. Southern Australia 457. Tasmania 56. Western Australia 1027, 1028, 1029, 1030. 6 OCEANIA Federated States of Micronesia 1056, 1058. Federated States of Micronesia Pohnpei I. 503, 808, 1058. Federated States of Micronesia Yap 424, 425, 504. Fiji 191. New Zealand 26, 26, 220. New Zealand Cape Karikari, North I. 294, 295, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341. Palau, Oceania 135, 136, 137, 138, 296, 433. Palau, Oceania Palau, Western Caroline I. 376. Papua New Guinea 382, 457, 681. Papua New Guinea Kimbe Bay 289, 290. Papua New Guinea Pass Reef of Madang 1075, 1076, 1078. Solomon Is. 382, 410, 414, 426, 427, 457. Vanuatu 973, 974, 975. 7 EUROPE Adriatic Sea 219, 355. Adriatic Sea, Italy Adriatic Sea 482. English English Channel 46. France Brittany 353. France Cap Martin 52, 53. Mediterranean Sea 201, 204, 207, 219, 365, 365, 370, 388, 404, 405, 406, 511, 512, 513, 514, 534, 535, 536, 842, 1050, 1051, 1052, 1053, 1054, 1055. Mediterranean Sea Monaco region of Mediterranean Sea 55. North Sea 482. Spain 46.

439

Spain Cádiz 5, 6, 7. Spain Canary Is. 261. 8 AFRICA Eritrea near Nakora I., Dahlak Archipielago, Red Sea 434, 435. Madagascar Nosy Be Is. 434. Morocco 354. Mozambique 629. Mozambique near Ponto Malongane 363. South Africa 844, 846, 940, 941. Tanzania Pemba I. 363, 364. 9 USA California, USA 23, 68. California, USA Pt. Loma 351, 416. Florida, USA 142, 145. Florida, USA Boca Raton 987, 988, 989, 990. Florida, USA Florida Keys 786. Guam, USA 143, 144, 196, 202, 205, 212, 213, 221. Hawaii, USA 257, 271, 303, 691. Hawaii, USA Hawaii, Black Point 25. Kwajalein Atoll 143, 144. La Jolla, USA 81, 82. La Jolla, USA 400 miles northwest of La Jolla 22. Puerto Rico 232, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 821, 920, 922, 944, 945, 946, 947, 948. Puerto Rico Mona I. 622, 625, 748, 749, 762, 949. Puerto Rico near La Parguera 128, 263, 266, 268, 487, 488, 489, 491, 492. 10 NORTH AMERICA Canada Nova Scotia 510. Canada Vancouver 199, 200. Panama Bocas del Toro, Caribbean Sea 820, 822, 949. 11 CARIBBEAN SEA Bahamas Caribbean Sea 175, 211, 362, 366, 367, 373, 374, 788. Bahamas Bimini Is. 96, 623. Bahamas Sweeting Cay, Grand Bahama I. 472. Caribbean Sea 51, 63, 64, 65, 66, 89, 93, 114, 116, 119, 120, 152, 158, 208, 209, 211, 361,

440

Index 4 Compound Sampling Geographic Locality Index

617, 618, 690, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 763, 764, 765, 779, 780, 781, 782, 783, 795. Dominica 127, 208, 209. Dominica Lauro Club Reef, Dominica, Caribbean Sea 208, 209. Jamaica 639. Tobago 34. 12 SOUTH AMERICA Brazil 160, 265, 269, 593. Chile 43, 44, 45. Columbia 554, 555, 556, 787. Colombia Old Providence I. 774. Colombia Santa Marta Bay, Caribbean Sea 115, 646, 647. 13 PACIFIC OCEAN Marshall Is., Pacific Ocean Enewetak Atoll, Marshall Is. 925, 927. New Caledoinia (Fr.) 134. Northern Pacific Ocean 1119, 1120. Oahu 264, 265.

Pacific Ocean 375, 376, 408, 420, 421, 422, 433. Western Pacific Ocean 976. 14 ATLANTIC OCEAN Atlantic Ocean near South Georgia I. 246, 247, 248, 249, 342, 343. Atlantic Ocean, Morocco Atlantic coast 407, 953. 15 ANTARCTIC/ARCTIC Antarctic 8, 21, 38, 41, 42, 154, 210, 437, 438, 439, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 627, 628. Antarctic Antarctic Ocean 164, 165, 167, 168, 169. Antarctic Antarctic south coast of England 37. Antarctic Antarctic, along Anvers Islclose to Palmer Station 440. Antarctica Anvers I. 530, 531. Antarctica Eastern Weddell Sea, Western Antarctica 141. Arctic 465.

Index 5 Compound Pharmacological Activity Index In this index, a set of very formatted pharmacological activity codes have been used, specially for all types of cancer cells, please see “List of Cancer Cells Codes”. A special note is that the word “Cytotoxic” means in vitro anticancer activities, while the word “Antineoplastic” means in vivo anticancer activities. A A anticancer drug target implicated in apoptosis 175. Abscission-accelerating substance 76. Acaricide 44, 45. Acetylcholine esterase inhibitor 715. Acetylcholine-histamine antagonist 359, 358. Activator of SHIP1 808. Active in an anti-quorum-sensing bioassay 646, 647. α1-Adrenergic blockade 414. Algicide 15, 37, 39, 87, 88, 261, 273, 309, 313, 377, 415, 416, 589, 624, 733. Alzheimer’s Disease AD is a multifactorial neurodegenerative disorder, main 10 scientific hypotheses show in details (Russo, 2016) 521. Androgen antagonist 461. Antagonist of plant growth hormones 76. Anthelmintic 191. Anthelmintic, parasitant stage of Nippostrongylus brasiliensis 269, 271. Anti-AD, preclinical trial 521. Antiangiogenic 464. Antibacterial 15, 39, 43, 46, 48, 261, 312, 371, 372, 381, 623. Antibacterial inactive, Bacillus cereus 86, 99, 110, 112. Antibacterial inactive, Bacillus megaterium 1064, 1069. Antibacterial inactive, Bacillus subtilis 86, 112. Antibacterial inactive, Chromobacterium violaceum 288. Antibacterial inactive, Escherichia coli 99. Antibacterial inactive, inhibits bioluminescence reaction 202, 205, 212, 221. Antibacterial inactive, Micrococcus tetragenus 99. Antibacterial inactive, Proteus mirabilis 288.

Antibacterial inactive, Sarcina lutea 86, 99, 100, 112. Antibacterial inactive, Staphylococcus albus 86, 110. Antibacterial inactive, symbiotic luminous bacterium Photobacterium leiognathi of tropical fish 202, 205, 212, 221. Antibacterial inactive, Vibrio anguillarum 86, 99, 100, 112. Antibacterial inactive, Vibrio cholera 288. Antibacterial inactive, Vibrio parahaemolyticus 86, 99, 100, 112. Antibacterial, Alcaligenes aquamarinus 256. Antibacterial, Azomonas agilis 256. Antibacterial, Azotobacter beijerinckii 256. Antibacterial, Bacillus cereus 100. Antibacterial, Bacillus megaterium 37, 1061, 1063, 1065, 1066, 1067, 1068, 1069, 1082, 1100, 1101, 1103. Antibacterial, Bacillus subtilis 99, 100, 110, 147, 148, 149, 150, 151, 220, 320, 321, 376, 411, 412, 428, 429, 430, 431, 432, 465, 529. Antibacterial, Bacillus subtilis ATCC 6633 291, 297, 299. Antibacterial, broad spectrum gram-positive and -negative bacteria both aerobes and anaerobes 422. Antibacterial, Chromobacterium violaceum 287. Antibacterial, Enterobacter aerogenes ATCC13048 282. Antibacterial, Erwinia amylovora 256. Antibacterial, Escherichia coli 86, 100, 110, 112, 198, 256, 411, 412, 428, 429, 430, 431, 432, 465, 1064, 1065, 1066, 1067, 1068, 1069, 1082, 1100, 1101, 1103. Antibacterial, gram-negative bacteria 530, 531. Antibacterial, gram-positive bacteria 118, 730, 732.

442

Index 5 Compound Pharmacological Activity Index

Antibacterial, inhibits bioluminescence reaction 213. Antibacterial, Klebsiella pneumonia 942, 943, 950, 951. Antibacterial, marine gram-positive bacteria 647. Antibacterial, Micrococcus luteus 302, 411, 412, 428, 429, 430, 431, 432. Antibacterial, Micrococcus tetragenus 86, 100, 110, 112. Antibacterial, Mycobacterium vaccae 147, 148, 149, 150, 151. Antibacterial, Salmonella enteritidis 543, 545, 546, 601, 602, 603, 604, 605, 739, 740. Antibacterial, Salmonella enteritidis ATCC13076 282. Antibacterial, Salmonella sp. 124. Antibacterial, Sarcina lutea 110. Antibacterial, Serratia marcescens ATCC25419 282. Antibacterial, Shigella sonnei ATCC11060 282. Antibacterial, Staphylococcus albus 99, 100, 112. Antibacterial, Staphylococcus aureus 54, 90, 92, 93, 101, 111, 113, 124, 198, 376, 407, 411, 412, 428, 429, 430, 431, 432, 433, 465, 953, 954. Antibacterial, Staphylococcus aureus ATCC 29213 291, 297, 299. Antibacterial, Staphylococcus epidermis 422. Antibacterial, Staphylococcus sp. 124, 258. Antibacterial, symbiotic luminous bacterium Photobacterium leiognathi of tropical fish 213. Antibacterial, Vibrio anguillarum 90, 92, 93, 110. Antibacterial, Vibrio cholera 124. Antibacterial, Vibrio parahaemolyticus 110. Antibacterial, VREF 8. Antibacterial, Yersinia enterocolitica ATCC23715 282. Antibarnacle, larval antisettlement agent and development inhibitor 191. Antibiotic 49, 69, 70, 71, 126, 141, 159, 327. Antibiotic, very effective 133. Anticontractive 358, 359, 360. Anticonvulsant 39, 384. Antifeedant 36, 68, 75, 79, 145, 200, 202, 243, 251, 266, 369, 486, 1010.

Antifeedant, aphids 274. Antifeedant, Brontispa longissima, an insect pest of coconut palms 483, 484, 485. Antifeedant, Eupomacentrus leucostictus 60, 61. Antifeedant, fish 82, 84, 142, 143, 144, 206, 303, 304, 508, 593. Antifeedant, herbivorous fish Pomacentrus coeruleus 28, 29, 30, 31, 32, 33. Antifeedant, insect 213. Antifeedant, insects 505. Antifeedant, lepidopteran insect cutworm Spodoptera litura second-instar larvae 1097, 1098, 1099, 1108. Antifoulant 85, 115, 252, 253, 254, 266, 615, 691, 733. Antifoulant inactive, to larval mortality 422. Antifoulant, barnacle 864. Antifoulant, barnacle Balanus amphitrite 222, 734, 738, 803, 804, 805, 806, 807, 823, 841, 914, 915, 1110. Antifoulant, barnacle Balanus amphitrite cypris larvae 224. Antifoulant, blue mussel Mytilus edulis 296. Antifoulant, blue mussel Mytilus galloprovincialis 296. Antifoulant, bryozoan Bugula neritina 737, 738. Antifoulant, Chlorella fusca 37. Antifoulant, inhibits barnacle larval settlement 1115, 1121, 1122. Antifoulant, inhibits larval settlement of Balanus amphitrite with low cytotoxicity 686, 687. Antifoulant, inhibits settlement of cypris larvae of barnacle Balanus amphitrite strongly 422. Antifoulant, larvae of acorn barnacle Balanus amphitrite 1108. Antifoulant, larval settlement of barnacle Balanus amphitrite at nontoxic concentrations 1102, 1104, 1105, 1106, 1107, 1109. Antifoulant, Ulva sp. spores 409. Antifoulant, US Navy program 1102, 1104, 1105, 1106, 1107, 1109. Antifoulant, US Navy program, larval settlement of barnacle Balanus amphitrite 1100, 1101, 1103.

Index 5 Compound Pharmacological Activity Index

Antifoulant, US Navy program, larval settlement of barnacle Balanus amphitrite at nontoxic concentrations 1087. Antifungal 20, 21, 23, 38, 40, 41, 42, 45, 46, 47, 49, 124, 125, 129, 189, 193, 243, 261, 270, 273, 373, 374, 530, 531. Antifungal inactive, Aspergillus flavus 291, 297, 299. Antifungal inactive, Aspergillus fumigatus 291, 297, 299. Antifungal inactive, Candida albicans 291, 297, 299. Antifungal inactive, Microbotryum violaceum 1064, 1068, 1103. Antifungal inactive, Saccharomyces cerevisiae 425. Antifungal, Aspergillus niger 376, 411, 412, 420, 424, 428, 429, 430, 431, 432. Antifungal, Candida albicans 292, 376, 411, 412, 428, 429, 430, 431, 432, 433. Antifungal, Candida utilis 376, 433. Antifungal, Cryptococcus neoformans 411, 412, 428, 429, 430, 431, 432. Antifungal, Eurotium repens 176. Antifungal, Inhibits RS321 636. Antifungal, Microbotryum violaceum 1066, 1082, 1065, 1067, 1069, 1100, 1101. Antifungal, Mycotypha microspora 37, 176. Antifungal, Neurospora crassa 204, 216. Antifungal, Saccharomyces cerevisiae 139, 335, 376, 420, 421, 424, 433. Antifungal, Septoria tritici 1061, 1063, 1064, 1065, 1066, 1067, 1068, 1069, 1082, 1100, 1101, 1103. Antifungal, Trichophyton mentagrophytes 220, 301, 411, 412, 428, 429, 430, 431, 432. Antifungal, Ustilago violacea 37, 176, 558. Anti-HCMV inactive, confluent HEL cells 964, 965. Anti-HCMV, confluent HEL cells 963, 966. Anti-HIV 48, 597, 656, 657. Anti-HIV-1, cell-based assay, inhibits cytopathic effect of HIV-1 infection 596. Antihypertensive 359, 360, 358. Anti-infective 243. Anti-inflammatory 72, 308, 393, 472, 532, 537, 538, 539, 540, 541, 542, 554, 555, 556, 717, 718, 792, 793, 796, 797, 798, 803, 824, 826, 844, 848, 848, 849, 850, 851, 851,

443

853, 859, 859, 860, 860, 861, 861, 862, 862, 863, 915, 940, 941, 976, 991, 992, 993, 994, 995, 1035, 1036, 1038, 1039, 1042, 1043, 1044, 1045, 1050, 1051, 1052, 1053, 1054, 1055, 1075, 1076, 1077, 1078, 1079, 1084, 1088, 1089, 1090, 1092, 1093, 1094, 1095, 1123. Anti-inflammatory hmn neutrophils, inhibits generation of superoxide anion 648. Anti-inflammatory immunoblot analysis assay, RAW264.7 cells, inhibition of LPS induced upregulation of iNOS and COX-2 586. Anti-inflammatory, exceed potency of indomethacin 794. Anti-inflammatory, fMLP/CB-induced hmn neutrophils 863. Anti-inflammatory, fMLP/CB-induced hmn neutrophils, elastase release inhibitor 893, 894, 895, 896, 897, 898, 899, 905, 912, 928, 961, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006. Anti-inflammatory, hmn neutrophils in response to fMLP/CB, elastase release inhibitor 652, 1085, 1086, 1087, 1046, 1047, 1048, 1049. Anti-inflammatory, hmn neutrophils in response to fMLP/CB, inhibits superoxide anion O2•− generation 1085, 1086, 1087. Anti-inflammatory, hmn neutrophils in response to fMLP/CB, superoxide anion O2•− generation 1046, 1047, 1048, 1049. Anti-inflammatory, hmn neutrophils, elastase release inhibitor 1013, 1014. Anti-inflammatory, hmn neutrophils, inhibits generation of superoxide anion 649, 650, 651, 652. Anti-inflammatory, hmn neutrophils, response to fMLP/CB, superoxide anion O2•− generation inhibitor 829, 831, 832, 833. Anti-inflammatory, immunoblot analysis, RAW264.7 cells, inhibition of LPS induced upregulation of iNOS and COX-2 584, 585, 590, 660, 661, 730. Anti-inflammatory, inhibitor of superoxide anion generation 897, 899, 905, 961, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006.

444

Index 5 Compound Pharmacological Activity Index

Anti-Inflammatory, inhibits accumulation of iNOS 800, 913. Anti-inflammatory, inhibits accumulation of pro-inflammatory proteins iNOS and COX-2 656, 696. Anti-inflammatory, Inhibits expression of iNOS and COX-2 in LPS-stimulated RAW264.7 cells 865, 866, 868, 869, 870. Anti-inflammatory, inhibits expression of iNOS in LPS-stimulated RAW264.7 cells 867. Anti-inflammatory, iNOS and COX-2s expression inhibitor, in macrophages 886. Anti-inflammatory, iNOS expression inhibitor in macrophages 884, 885. Anti-inflammatory, LPS-induced mouse RAW264.7 macrophage cell, IL-6 release inhibitor 872. Anti-inflammatory, LPS-stimulated murine macrophage cells, inhibits up-regulation of iNOS and COX-2s 579, 580. Anti-inflammatory, LPS-stimulated RAW264.7 cells, doesn’t inhibit up-regulation of COX2 but inhibis iNOS 545. Anti-inflammatory, LPS-stimulated RAW264.7 cells, doesn’t inhibit up-regulation of COX2, but inhibis iNOS, MMOA - iNOS and COX-2 inhibition 602. Anti-inflammatory, LPS-stimulated RAW264.7 cells, doesn’t inhibit up-regulation of COX2, but inhibis iNOS 604, 605. Anti-inflammatory, LPS-stimulated RAW264.7 cells, inhibits accumulation of COX-2, reduces level of COX-2 239, 240, 241, 242. Anti-inflammatory, LPS-stimulated RAW264.7 cells, inhibits expression of iNOS and induction of iNOS 709, 710, 711. Anti-inflammatory, LPS-stimulated RAW264.7 cells, inhibits iNOS and COX-2 expression, but for inhibition of β-actin protein with cytotoxic activity 543, 546. Anti-inflammatory, LPS-stimulated RAW264.7 cells, inhibits LPS-induced upregulation of iNOS and COX-2 192. Anti-inflammatory, LPS-stimulated RAW264.7 cells, inhibits up-regulation of iNOS and COX-2, protein β-actin is not changed 598.

Anti-inflammatory, LPS-stimulated RAW264.7 cells, inhibits up-regulation of iNOS, but doesn’t inhibit COX-2 expression, protein β-actin is not changed 599. Anti-inflammatory, LPS-stimulated RAW264.7 cells, inhibits up-regulation of iNOS and COX-2, protein β-actin is not changed 600. Anti-inflammatory, LPS-stimulated RAW264.7 cells, inhibits up-regulation of iNOS and COX-2, MMOA - iNOS and COX-2 inhibition 603. Anti-inflammatory, LPS-stimulated RAW264.7 cells, inhibits up-regulation of iNOS 694. Anti-inflammatory, LPS-stimulated RAW264.7 cells, inhibits up-regulation of COX-2 735. Anti-inflammatory, LPS-stimulated RAW264.7 cells, inhibits up-regulation of iNOS and COX-2 736, 739, 740, 931. Anti-Inflammatory, LPS-stimulated RAW264.7 cells, reduces COX-2 expression 906. Anti-Inflammatory, LPS-stimulated RAW264.7 cells, reduces expression of COX-2 913. Anti-inflammatory, microglial cells, reduced iNOS expression without cytotoxicity 744. Anti-inflammatory, NO production inhibitor, LPS-stimulated macrophages 820, 822. Anti-inflammatory, RAW264.7 cells, iinhibition of LPS induced upregulation of iNOS 563. Anti-inflammatory, RAW264.7 cells, inhibition of LPS induced upregulation of COX-2 562. Anti-inflammatory, RAW264.7 cells, inhibition of LPS induced upregulation of COX-2 and iNOS 595. Anti-inflammatory, RAW264.7 cells, inhibition of LPS induced upregulation of iNOS 746, 747, 888, 889, 890, 891, 912. Anti-inflammatory, RAW264.7 cells, inhibition of LPS induced upregulation of iNOS, inhibited iNOS 876, 877, 878, 879, 880. Anti-inflammatory, RAW264.7 cells, inhibition of LPS induced upregulation of iNOS and COX-2, inhibited iNOS and COX-2 882, 883. Anti-inflammatory, reduced level of iNOS and COX-2 282. Anti-inflammatory, superoxide anion O2•− generation and elastase release by hmn

Index 5 Compound Pharmacological Activity Index

neutrophils, MMOA - superoxide anion and elastase inhibition 1040, 1041. Anti-inflammatory, superoxide anion O2•− generation inhibitor 834, 939. Anti-inflammatory, superoxide anion O2•− generation inhibitor, fMLP/CB stimulated neutrophils 982, 983. Anti-inflammatory, TPA-induced mouse ear edema assay 115. Anti-invasive activity, PC3 874, 916, 921, 925, 926. Antimalarial 771, 772, 773, 774. Antimalarial, Plasmodium falciparum 410, 427. Antimicroalgal, Brachiomonas submaria [Chlorophyceae] 409. Antimicroalgal, Oscillatoria amphibian [Cyanophyceae] 409. Antimicroalgal, Prorocentrum micans [Dinophyceae] 409. Antimicroalgal, Skeletonema costatum [Diatomophyceae] 409. Antimicrobial 26, 52, 80, 91, 94, 125, 127, 129, 222, 225, 357, 375, 408, 418, 527, 528. Antimicrobial, wide range 719. Antimicrobial, wide spectrum 326. Anti-migration, PC3 801, 826, 843, 874, 916, 917, 918, 919, 921, 925, 926, 927. Antimitotic 274. Antimutagenic 266, 273. Antimycobacterial 77, 132, 259, 266, 459, 460, 638. Antineoplastic, in vivo 49, 89, 96, 140, 312, 326, 846. Antineoplastic, in vivo, P388 564. Antinociceptive 213. Antioxidant, DPPH radical scavenger 456. Antioxidant, superoxide anion ∙O2– scavenger 229, 394, 419, 436, 653. Antiplasmodial, CRPF FcB1 954. Antiplasmodial, CRPF W2 116, 119, 120, 152, 158, 775, 776, 777, 789, 790, 791. Antiplasmodial, CSPF D6 194. Antiplasmodial, Plasmodium falciparum 280, 281, 422, 426, 810, 811, 813, 814, 815, 816, 817, 819, 821, 920, 922. Antiproliferative inactive, IGR-1 365. Antiproliferative inactive, J774 365. Antiproliferative inactive, P388 365. Antiproliferative inactive, WEHI-164 365, 365.

445

Anti-proliferative, DU145 627. Antiproliferative, K562 310, 313, 315, 316, 317, 318, 329. Antiproliferative, L929 310, 313, 315, 316, 317, 318, 329. Antiproliferative, MCF7 627. Antiproliferative, WEHI-164 388. Antipsoriatic 718, 717. Antispasmodic 371, 372. Antitrypanosomal, Trypanosoma brucei 289, 290. Antituberculosis 375. Antituberculosis, inhibits some drug-resistant strains of Mycobacterium tuberculosis 376. Antituberculosis, Mycobacterium tuberculosis 422. Antituberculosis, Mycobacterium tuberculosis H37Rv 114, 120, 152, 158, 376, 787, 810, 814, 818, 920. Antitumour promoter 717, 720. Antitumour promoting activity 199, 200. Antiviral 509, 611, 612, 613, 1050, 1051, 1052, 1053, 1054, 1055, 1123. Antiviral inactive, HSV 264. Antiviral, hmn cytomegalovirus 549. Antiviral, hmn cytomegalovirus HCMV 607, 608, 609, 621. Antiviral, hmn embryonic lung HEL cell line 608, 609, 621. Antiviral, HSV virus 265. ATPase inhibitor 375, 376, 408, 433, 715. B Biofilm formation and biofouling inhibitor 962. Blocker of AP-1 activation 537, 540. Blocker of NF-κB activation 393, 537, 538, 539, 540, 541, 542. C Ca2+-channel antagonistic action 414. Ca2+-channel antagonistic action and α1 adrenergic blocker 413. Calcium antagonist 589, 638. cAMP inhibitor 803. cAMP PDE inhibitor 826, 824. Cardiotoxic 323. Cell cleavage inhibitor 799. Cell cycle regulators 810, 814. Cell division inhibitor 795.

446

Index 5 Compound Pharmacological Activity Index

Cell division inhibitor, fertilized sea urchin eggs 233. Cell growth inhibitor 413, 656. Cell growth/division Inhibitor, fertilised sea urchin eggs 389, 390. Cell proliferation inhibitor 927, 871. Cell-adhesion inhibitor 171, 172, 173, 177, 178, 179, 283. Cell-adhesion inhibitor, immune system activity 174. Cell-adhesion inhibitor, inhibits adhesion of HL60 cells to HUVEC cells 180, 181. CNS depressant 981. Convulstant, less active than picrotoxinin 284. COX-2 proinflammatory proteins 630. Cytoprotective, cells injured with H2O2 767, 768. Cytotoxic 50, 77, 79, 93, 155, 185, 186, 195, 235, 236, 237, 291, 299, 305, 357, 380, 395, 396, 397, 398, 399, 414, 509, 543, 546, 551, 552, 553, 595, 617, 618, 623, 630, 639, 640, 697, 698, 699, 700, 701, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 765, 781, 782, 783, 785, 786, 799, 802, 803, 824, 846, 915, 942, 943, 944, 945, 946, 947, 948, 950, 951, 1128, 1131. Cytotoxic inactive, 786-0 382. Cytotoxic inactive, A278 311. Cytotoxic inactive, A2780CisR 482. Cytotoxic inactive, A375 684, 685, 686, 687, 688. Cytotoxic inactive, A549 65, 67, 86, 99, 100, 109, 110, 112, 122, 169, 184, 217, 219, 231, 323, 562, 563, 576, 577, 578, 594, 608, 609, 621, 676, 684, 685, 686, 687, 688, 717, 848, 849, 850, 851, 851, 853, 859, 860, 861, 862, 863, 876, 877, 879, 880, 881, 882, 883, 887, 892, 905, 913, 963, 964, 965, 966, 1008, 1015, 1016, 1018, 1021, 1022, 1023, 1027, 1029, 1030, 1031, 1032, 1033, 1034, 1037, 1062, 1064, 1065, 1066, 1082, 1083, 1097, 1098, 1099, 1103, 1117. Cytotoxic inactive, A549/ATCC 382. Cytotoxic inactive, B16 9, 10, 11, 12, 121. Cytotoxic inactive, BEAS2B 892, 913. Cytotoxic inactive, BGC823 214, 215, 684, 685, 686, 687, 688.

Cytotoxic inactive, BT-483 892. Cytotoxic inactive, Ca9-22 847, 851, 881, 887. Cytotoxic inactive, CCRF-CEM 116, 829, 830, 831, 833, 929, 935, 936, 938, 1095. Cytotoxic inactive, CHO-K1 232. Cytotoxic inactive, DLD-1 586, 590, 730, 829, 831, 833, 1091, 1095. Cytotoxic inactive, Doay 634, 635, 692, 693, 694, 695, 706, 735, 736, 929, 930, 931. Cytotoxic inactive, DU145 419, 436. Cytotoxic inactive, G402 311, 314. Cytotoxic inactive, GXF-251L 209. Cytotoxic inactive, H1299 892, 913. Cytotoxic inactive, HCT8 684, 685, 686, 687, 688. Cytotoxic inactive, HCT116 586. Cytotoxic inactive, HEL 608, 609, 621, 676, 964, 965, 966. Cytotoxic inactive, HeLa 232, 566, 567, 568, 570, 572, 631, 634, 635, 692, 693, 694, 695, 735, 736, 809, 812, 929, 930, 931. Cytotoxic inactive, Hep2 634, 635, 692, 693, 694, 695, 706, 735, 736, 929, 930, 931. Cytotoxic inactive, Hep3B 881. Cytotoxic inactive, HepG2 648, 650, 651, 656, 684, 685, 686, 687, 688, 881, 887, 892, 913. Cytotoxic inactive, HepG2, Hep3B, MDA-MB231, MCF7 and A549 579, 580. Cytotoxic inactive, HL60 86, 99, 100, 110, 112, 116, 169, 218, 294, 311, 314, 337, 338, 586, 684, 687, 688, 829, 830, 835, 836, 837, 838, 839, 840. Cytotoxic inactive, HT115 314. Cytotoxic inactive, HT29 65, 67, 109, 122, 184, 231, 323, 576, 577, 578, 594, 608, 609, 621, 657, 676, 717, 851, 863, 964, 965, 966, 1015, 1016, 1021, 1022, 1023, 1027, 1029, 1030, 1031, 1032, 1033. Cytotoxic inactive, Huh7 650, 651. Cytotoxic inactive, IGROV1 382. Cytotoxic inactive, K562 436, 482, 650, 651, 851, 863, 929, 935, 936, 938. Cytotoxic inactive, KB 567, 568, 570, 572, 573, 594, 717, 1016, 1021, 1022, 1023, 1032, 1033. Cytotoxic inactive, KM12 382. Cytotoxic inactive, KYSE70 363.

Index 5 Compound Pharmacological Activity Index

Cytotoxic inactive, KYSE180 363. Cytotoxic inactive, KYSE520 363. Cytotoxic inactive, L1210 138, 557. Cytotoxic inactive, LXF-526L 209. Cytotoxic inactive, LXF-H460 209. Cytotoxic inactive, MCF12 363. Cytotoxic inactive, MCF7 116, 311, 314, 458, 459, 462, 466, 467, 469, 470, 471, 631, 634, 635, 656, 690, 692, 693, 694, 695, 706, 735, 736, 851, 852, 881, 929, 930. Cytotoxic inactive, MDA-MB-231 585, 586, 656, 851, 881, 887. Cytotoxic inactive, MDCK 9, 10, 11, 12. Cytotoxic inactive, MEL28 65, 271, 1027, 1028, 1029, 1030. Cytotoxic inactive, MG63 1008, 1037, 1059, 1061, 1062, 1064, 1065, 1066, 1082, 1083, 1103, 1117. Cytotoxic inactive, Molt4 116, 929, 935, 936, 938. Cytotoxic inactive, NBT-T2 494, 495, 499, 500. Cytotoxic inactive, NCI-H460 458, 462, 463, 466, 467, 468, 469, 470, 471. Cytotoxic inactive, P388 65, 323, 387, 401, 403, 548, 557, 576, 577, 578, 676, 727, 851, 964, 965, 966, 1015, 1016, 1021, 1022, 1023, 1032, 1126. Cytotoxic inactive, P388D1 829, 830, 831, 833. Cytotoxic inactive, panel of NCI′s hmn tumour cell lines 16, 17, 35. Cytotoxic inactive, PC3 801, 826, 843, 874, 916, 917, 918, 919, 921, 925, 926, 927. Cytotoxic inactive, PS 128, 262, 263, 268. Cytotoxic inactive, RPMI8226 116. Cytotoxic inactive, SAS 892, 913. Cytotoxic inactive, SF268 458, 462, 466, 467, 468, 469, 470, 471. Cytotoxic inactive, T47D 929, 935, 936, 937, 938. Cytotoxic inactive, Vero 9, 10, 11, 12. Cytotoxic inactive, WHCO1 363. Cytotoxic inactive, WHCO5 363. Cytotoxic inactive, WHCO6 363. Cytotoxic inactive, WiDr 706, 709, 710, 711. Cytotoxic, A278 314. Cytotoxic, A2780 313, 482. Cytotoxic, A498 591. Cytotoxic, A549 5, 6, 7, 51, 63, 64, 66, 78, 104, 105, 106, 107, 108, 164, 165, 167, 168, 218,

447

257, 271, 298, 319, 344, 345, 346, 347, 348, 352, 434, 435, 547, 548, 559, 561, 574, 575, 654, 655, 656, 657, 659, 673, 674, 675, 677, 678, 696, 712, 725, 726, 800, 841, 847, 873, 875, 906, 970, 1017, 1019, 1020, 1024, 1025, 1026, 1028, 1059, 1060, 1061, 1067, 1068, 1069, 1070, 1071, 1072, 1073, 1074, 1100, 1101. Cytotoxic, A549 NSCL 435. Cytotoxic, anti-oesophageal cancers 363. Cytotoxic, antitumour, induces tubulin polymerization 923, 924. Cytotoxic, B16 481, 641, 642, 643, 644, 645. Cytotoxic, BEAS2B 800, 906. Cytotoxic, BT-483 800, 906, 913. Cytotoxic, BXF-1218L 208, 209. Cytotoxic, BXF-T24 208, 209. Cytotoxic, BXPC3 growth inhibitor 988, 989, 990. Cytotoxic, Ca9-22 579, 580, 656, 696, 873, 875. Cytotoxic, CaCo-2 973, 974, 975. Cytotoxic, CCRF-CEM 123, 590, 648, 649, 650, 651, 690, 730, 871, 927, 937, 1091, 1093, 1094. Cytotoxic, CCRF-CEM with some selectivity 170. Cytotoxic, CCRF-CEMT 761. Cytotoxic, CHO-K1 949. Cytotoxic, CNE2 319. Cytotoxic, CNXF-498NL 208, 209. Cytotoxic, CNXF-SF268 208, 209. Cytotoxic, CXF-HCT116 208, 209. Cytotoxic, CXF-HT29 208, 209. Cytotoxic, DLAT 308. Cytotoxic, DLD-1 419, 436, 584, 585, 741, 745, 830. Cytotoxic, Doay 192, 565, 566, 567, 568, 569, 570, 571, 572, 573, 587, 631, 632, 633, 702, 703, 704, 705, 707, 708, 709, 710, 711. Cytotoxic, DU145 435. Cytotoxic, EAC 291, 299, 308, 473, 474, 475, 476, 477, 478, 479, 480, 637, 716. Cytotoxic, echinoderms 417. Cytotoxic, farnesyl protein transferase FPT inhibitor 663. Cytotoxic, G402 313. Cytotoxic, GXF-251L 208.

448

Index 5 Compound Pharmacological Activity Index

Cytotoxic, H460 616, 718. Cytotoxic, H1299 800, 906. Cytotoxic, HCT15 352, 841. Cytotoxic, HCT29 78. Cytotoxic, HCT116 175, 211, 584, 585, 591, 690, 761, 788. Cytotoxic, HEL 659, 673, 674, 675, 677, 678. Cytotoxic, HeLa 163, 166, 214, 215, 275, 276, 277, 278, 279, 310, 313, 315, 316, 317, 318, 329, 565, 569, 571, 573, 587, 632, 633, 760, 761, 763, 764, 788, 949. Cytotoxic, Hep2 192, 246, 247, 248, 249, 587, 631, 632, 633, 702, 703, 704, 705, 707, 708, 709, 710, 711. Cytotoxic, Hep3B 851, 887, 847, 852, 656, 873, 875, 696. Cytotoxic, HepG2 275, 276, 277, 278, 279, 649, 696, 800, 851, 852, 873, 875, 906. Cytotoxic, high active 391. Cytotoxic, HL60 135, 164, 165, 167, 168, 214, 215, 217, 219, 295, 313, 330, 331, 332, 333, 334, 335, 336, 339, 340, 341, 382, 419, 436, 584, 585, 685, 686, 831, 833. Cytotoxic, hmn colon tumour cell lines 900. Cytotoxic, hmn embryonic stem cells BG02 growth inhibitor 987, 988, 989, 990. Cytotoxic, hmn tumour cell lines 12, 342, 343. Cytotoxic, HNXF-536L 208, 209. Cytotoxic, HT29 5, 6, 7, 51, 63, 64, 66, 78, 104, 105, 106, 107, 108, 246, 247, 249, 257, 271, 298, 344, 345, 346, 347, 348, 350, 434, 435, 435, 547, 548, 559, 561, 574, 575, 654, 655, 659, 673, 674, 675, 677, 678, 712, 725, 726, 727, 1007, 1017, 1018, 1019, 1020, 1024, 1025, 1026, 1028, 1034. Cytotoxic, HT29, potent 102, 103. Cytotoxic, HT115 313. Cytotoxic, HTC116 741. Cytotoxic, HTCLs cells 97, 98, 322, 689. Cytotoxic, Huh7 648, 649. Cytotoxic, IGROV-ET 435. Cytotoxic, inhibits cell division in fertilized sea urchin eggs 564. Cytotoxic, Jak2/STAT5-dependent hmn erythroleukemia cells 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455.

Cytotoxic, K562 214, 215, 311, 313, 314, 419, 518, 521, 522, 523, 524, 525, 526, 533, 648, 649, 741, 823, 914, 927, 937. Cytotoxic, KB 134, 503, 547, 560, 564, 565, 566, 569, 571, 574, 575, 614, 655, 712, 721, 722, 723, 724, 725, 726, 732, 969, 1015, 1017, 1018, 1019, 1020, 1024, 1025, 1026, 1031, 1034. Cytotoxic, KB16 104, 105, 106, 107, 108, 109. Cytotoxic, KM12 232. Cytotoxic, L1210 135, 136, 137, 423, 544, 550, 560, 564, 732. Cytotoxic, L5178Y 219, 482. Cytotoxic, LoVo 319, 419, 435, 436, 503. Cytotoxic, LXF-1121L 208, 209. Cytotoxic, LXF-289L 208, 209. Cytotoxic, LXF-526L 208. Cytotoxic, LXF-529L 208, 209. Cytotoxic, LXF-629L 208, 209. Cytotoxic, LXF-H460 208. Cytotoxic, majority of NCI ovarian tumour lines and several of renal, prostate and colon tumour lines 555, 556. Cytotoxic, MAXF-401NL 208, 209. Cytotoxic, MAXF-MCF7 208, 209. Cytotoxic, MCF7 192, 214, 215, 275, 276, 277, 278, 279, 313, 459, 460, 463, 468, 587, 616, 632, 633, 696, 702, 703, 704, 705, 707, 708, 709, 710, 711, 718, 761, 873, 875, 887, 931. Cytotoxic, MCF7, 100 μmol/L 1080, 1081. Cytotoxic, MDA-MB-231 584, 696, 741, 873, 875, 967. Cytotoxic, MDA-MB-435 275, 276, 277, 278, 279. Cytotoxic, MDR tumour cell lines 203. Cytotoxic, MEL28 5, 6, 7, 51, 63, 64, 66, 257, 434, 435, 435. Cytotoxic, MEXF-276L 208, 209. Cytotoxic, MEXF-394NL 208, 209. Cytotoxic, MEXF-462NL 208, 209. Cytotoxic, MEXF-514L 208, 209. Cytotoxic, MEXF-520L 208, 209. Cytotoxic, MG63 1060, 1067, 1068, 1069, 1070, 1071, 1072, 1073, 1074, 1100, 1101. Cytotoxic, mode of action is inhibition of proteasomes 208, 209.

Index 5 Compound Pharmacological Activity Index

Cytotoxic, Molt4 382, 419, 436, 648, 649, 650, 651, 741, 745, 766, 835, 836, 837, 838, 839, 840, 871, 927, 937. Cytotoxic, murine leukemia 78. Cytotoxic, N18-T62 627. Cytotoxic, NBT-T2 497, 501, 502. Cytotoxic, NCI primary disease-oriented antitumour screen 762, 779, 780. Cytotoxic, NCI/ADR-Res, potent 272. Cytotoxic, NCI-H322M 626. Cytotoxic, NCI-H460 459, 460. Cytotoxic, OVXF-899L 208, 209. Cytotoxic, OVXF-1619L 208, 209. Cytotoxic, OVXF-OVCAR3 208, 209. Cytotoxic, P388 4, 5, 6, 7, 51, 63, 64, 66, 67, 73, 104, 105, 106, 107, 108, 109, 122, 146, 156, 157, 161, 184, 231, 257, 271, 298, 300, 301, 344, 345, 346, 347, 348, 350, 385, 386, 400, 402, 434, 435, 435, 520, 544, 547, 549, 550, 560, 561, 574, 575, 594, 606, 608, 609, 610, 621, 655, 659, 673, 674, 675, 677, 678, 681, 682, 683, 712, 717, 725, 726, 732, 778, 827, 863, 969, 971, 972, 1007, 1017, 1018, 1019, 1020, 1024, 1025, 1026, 1027, 1028, 1029, 1030, 1031, 1033, 1034, 1124, 1125. Cytotoxic, P388, mixture with Plocamenone 3. Cytotoxic, PANC1 435. Cytotoxic, panel of 36 hmn tumour cell lines, mean IC50 = 0.114 μg/mL, extremely potent, displayed significant selectivity toward 12 of cell lines and possessed a unique cytotoxic selectivity pattern as determined by COMPARE analyses 208. Cytotoxic, panel of 36 hmn tumour cell lines, mean IC50 = 1.249 μg/mL 209. Cytotoxic, panel of NCI′s 60 hmn tumour cell lines, mean LC50 = 1.1 μg/mL 211. Cytotoxic, panel of NCI′s 60 hmn tumour cell lines, ovarian, renal and melanoma lines were particularly sensitive 325. Cytotoxic, panel of NCI′s 60 hmn tumour cell lines, weak differential cytotoxity 324. Cytotoxic, panel of NCI′s hmn tumour cell lines 625. Cytotoxic, panel of NCI′s hmn tumour cell lines, mean GI50 = 0.676 μmol/L 24. Cytotoxic, panel of NCI′s hmn tumour cell lines, mean GI50 = 0.691 μmol/L 13.

449

Cytotoxic, panel of NCI′s hmn tumour cell lines, mean GI50 = 0.741 μmol/L 19. Cytotoxic, panel of NCI′s hmn tumour cell lines, mean GI50 = 1.15 μmol/L 27. Cytotoxic, panel of NCI′s hmn tumour cell lines, mean GI50 = 1.32 μmol/L 25. Cytotoxic, panel of NCI′s hmn tumour cell lines, mean GI50 = 19.5 μmol/L 18. Cytotoxic, panel of NCI′s hmn tumour cell lines, mean GI50 = 21.9 μmol/L 34. Cytotoxic, panel of NCI′s hmn tumour cell lines, mean GI50 = 26.1 μmol/L 14. Cytotoxic, panel of NCI′s hmn tumour cell lines, moderate 622. Cytotoxic, panel of NCI′s tumour cell lines 272, 771. Cytotoxic, panel of renal carcinoma cell lines 211. Cytotoxic, panel of tumour cell lines 201, 207. Cytotoxic, PAXF-1657L 208, 209. Cytotoxic, PAXF-PANC1 208, 209. Cytotoxic, PBMC 518, 521, 522, 523, 524, 525, 526, 533. Cytotoxic, PC3 275, 276, 277, 278, 279. Cytotoxic, potent 828. Cytotoxic, PRXF-22RV1 208, 209. Cytotoxic, PRXF-DU145 208, 209. Cytotoxic, PRXF-LNCAP 208, 209. Cytotoxic, PRXF-PC3M 208, 209. Cytotoxic, PS (=P388) 266, 487, 488, 489, 491, 492, 732. Cytotoxic, PXF-1752L 208, 209. Cytotoxic, RXF-1781L 208, 209. Cytotoxic, RXF-393NL 208, 209. Cytotoxic, RXF-486L 208, 209. Cytotoxic, RXF-944L 208, 209. Cytotoxic, S180 637, 716. Cytotoxic, SAS 800, 906. Cytotoxic, sea urchin Strongylocentrotus eggs 473, 474, 475, 476, 478. Cytotoxic, second-instar larvae of lepidopteran insect cutworm Spodoptera litura 1097, 1098, 1099, 1108. Cytotoxic, selective growth inhibition activity 788. Cytotoxic, SF268 459, 460, 463, 616, 718. Cytotoxic, similar with Flabellatene A 628. Cytotoxic, SK5-MEL 591. Cytotoxic, SK-MEL-2 352, 841.

450

Index 5 Compound Pharmacological Activity Index

Cytotoxic, SK-OV-3 352, 841. Cytotoxic, SR 766. Cytotoxic, T47D 741, 871, 927. Cytotoxic, three different cells 162. Cytotoxic, TK10 626. Cytotoxic, tMDA-MB-231, 100 μmol/L 1080, 1081. Cytotoxic, to ciliates 59, 83. Cytotoxic, UXF-1138L 208, 209. Cytotoxic, variety of tumour cells 170. Cytotoxic, WiDr 192, 702, 703, 704, 705, 707, 708. Cytotoxic, with microtubule stabilising props, potent, preclinical evaluation in 2001, no longer being pursued due to lack of material availability 845. Cytotoxic, XF498 352.

Enzyme inhibitor 326.

D Defensive agent 293, 306, 307. Defensive metabolite 141, 154. Defensive secretion 368, 383. Differential Cytotoxicity, softagar assay, zone differential of 250 units is expected for “selectiveactivity”, M17-L1210 382, 457.

G GABAA receptor antagonist 284.

E EGFR tyrosine kinase inhibitor 521, 522, 523, 524, 525, 526, 533. Elastase inhibitor 117, 828. Elastase release inhibitor 829, 831, 832, 833, 834, 859, 860, 861, 862, 939, 982, 983. Elastase release inhibitor stimulated hmn neutrophils 436. Elastase release inhibitor stimulated hmn neutrophils, response to fMLP/CB 394, 419. Elastase release inhibitor, fMLP/CB-induced hmn neutrophils 851, 863. Elastase release inhibitor, hmn neutrophils 1011, 1012. Elastase release inhibitor, hmn neutrophils, response to formyl-Met-Leu-Phe/ cytochalasin B fMLP/CB 648, 649, 650, 651. Elastase release inhibitor, stimulated hmn neutrophils, response to fMLP/CB 229, 653. Endothelin receptor binding agent 201.

F Facilitator of neuromuscular transmission 589. Fat-accumulation inhibitor, 3T3-L1 murine adipocytes, inhibition of triglyceride accumulation, along with cytotoxicity 190. Feeding deterrent, Carassius auratus 197. Feeding-inhibitor, young abalone Haliotis diskus hannai, sea urchins Stronglyocentrotus nudus and Stronglyocentrotus intermedius 490. fMLP/CB-induced hmn neutrophils 859, 860, 861, 862. For significant activity ED50 ≤ 4.0 μg/mL is required 1020.

H H/K-ATPase inhibitor 95. Haemolytic 909, 912. Helicocide 213. Hemolytic 911, 907. Histamine release inhibitor 717, 718. Histidine decarboxylase inhibitor 923, 924. Hyperplasia 717. Hypotensive 679. I Ichthyodeterrent activity 619. Ichthyotoxic 124, 125, 129, 130, 131, 155, 199, 200, 356, 496, 506, 507, 515, 516, 527, 658, 662, 784, 785, 911, 912, 960, 1129, 1130. Ichthyotoxic, lethal to goldfish Carassius auratus 376. Ichthyotoxin 56, 57, 79, 84, 145, 202, 234, 251, 285, 286, 351, 377, 378, 379, 415, 416, 433, 519, 564, 574, 588, 592, 691, 713, 715, 907. Ichtyotoxic 532. Ichtyotoxin 22. Inhibits predation by local predatory sea star Odontaster validus 141. IL-12, IL-6 and TNF-α production inhibitors, LPS-stimulated bone marrow dendritic cells 742, 743.

Index 5 Compound Pharmacological Activity Index

Immune system activity, murine spleen cell lysosome activation 493, 498. Immunodepressant 228. Immunomodulator 1056, 1057, 1058, 1116. Increases cardiac output at high dose 1009. Induces apoptosis, transformed mammalian cells 364. Induces glutathione-S-transferase 716. Induces quinone reductase 716. Inhibition of adenosine transfer into rabbit erythrocytes 414. Inhibitor of binding of DHT to androgen receptor 461. Inhibitor of superoxide anion generation 851, 859, 860, 861, 862, 863. Inhibits [3H]CPDPX binding to ratbrain adenosine A1 receptor 955, 956, 957, 958, 959. Inhibits accumulation of iNOS simulated macrophages 581, 582, 583. Inhibits cAMP PDE 915. Inhibits cell cleavage of sea urchin eggs 574. Inhibits cell division, fertilised starfish eggs 803, 915. Inhibits cell division, fertilized sea urchin eggs 354. Inhibits chymotrypsin-like, caspase-like and trypsin-like activity of purified 20S-proteasomes 208, 209. Inhibits CYP450 1A 716. Inhibits development of fertilized sea urchin eggs 353. Inhibits expression of cyclooxygenase-2 321. Inhibits expression of iNOS macrophages 697, 698, 699, 700, 701. Inhibits expression of nitric oxide synthase 321. Inhibits first cleavage of fertilized sea urchin eggs 400, 401, 402, 403. Inhibits hmn neutrophil elastase HNE release neutrophil, response to fMLP/CB 968. Inhibits interaction of oncogenic transcription factor Myc with its partner protein Max 313. Inhibits Jak2, STAT5 and Erk1/2 activation in hmn erythroleukemia cells and causes apoptosis 449.

451

Inhibits mitochondrial respiratory chain 223, 227. Inhibits nucleoside transport into erythrocytes, rbt 413. Inhibits pentobarbital metabolism 328. Inhibits pro-inflammatory cytokine TNFα released from Raw264.7 cells 393, 537, 538, 539, 540, 541, 542. Inhibits synthesis of PGE2 and LTB4 554. Inhibits synthesis of prostaglandinE2 and leukotriene LTB4 555. Inhibits up-regulation of LPS-induced iNOS 702, 703, 704, 705, 706, 707, 708. Inhibits VEGF-A dependent endothelial cell sprouting 482. iNOS accumulation inhibitor, stimulated macrophages 932, 933, 934. iNOS expression inhibitor, macrophages 769, 770. Inotropic activity blocker 359. Insect growth regulator 213. Insect repellant 243. Insecticide 20, 36, 39, 44, 45, 140, 260, 274, 671, 823, 824, 902, 903, 980, 1056, 1057, 1096, 1118, 1119. Insecticide, larvae of pest insect Spodoptera littoralis 226, 230. Insecticide, silkworm Bombyx mori 901. Irreversibly inhibits binding of α-toxin to nicotinic acetylcholine receptor 552. K Kinase EGFR inhibitor 518, 522, 523, 525. L LD50 686, 687, 841. LD50 brine shrimp 238, 349. LD50 ichthyotoxin 663. LD50 mus ipr 285, 358. LD50 mus ivn 323. LD50 mus scu 691. LD50 rat orl 1, 2, 76, 225. LD50 rbt skn 1. Less active by several orders of magnitude than 3-Acetyl-13-deoxyphomenone 162. Lethal activity against Ulva fronds 409. 5-Lipoxygenase inhibitor 153.

452

Index 5 Compound Pharmacological Activity Index

LTB4 receptor partial agonist 250.

Noxious to Antarctic fish 417.

M Metalloprotease collagenase IV inhibitor 510. Mode of action is via influence of Golgi function and Golgi vesicle formation 335. Morphogenetic hydra tentacle regeneration agent 511, 512, 513, 514, 534, 535, 536. Muscle relaxant 671. Mutagen 53. Mutagenic 55. Mycotoxin 327.

O Only had an effect on iNOS expression 930. Ornithine decarboxylase inhibitor 717.

N Na/K-ATPase inhibitor 205, 372, 421, 422. Na/K-ATPase inhibitor inactive 196, 213. Na/K-transporting ATPase inhibitor 420. Nematocidal, two pathogens of sheep and other ruminants larval stages of parasitic nematodes Haemonchus contortus and Trichostrongylus colubriformis 520. Nematocide 671. Neuromuscular toxin 671. Neuromuscular transmission inhibitor 323. Neuroprotectant 719. Neuroprotective, neuroblastoma SH-SY5Y cells, reduces 6-OHDA neurotoxicity 182, 183, 187, 188. neuroprotective, neuroblastoma SH-SY5Y, damage of 6-OHDA-induced 744. Neurotransmitter receptor inhibitor 794. NF-κB inhibitor 62, 74, 244, 245. NF-κB inhibitor, cell-based HEK-293 NF-κB luciferase reporter gene assay 730. NF-κB plays a key role in regulating immune response to infection, incorrect regulation of NF-κB has been linked to cancer, inflammatory, autoimmune diseases, septic shock, viral infection and improper immune development 730. Nicotinic acetylcholine receptor antagonist 794. No effects to accumulation of COX-2 192. NO production inhibitor, LPS-stimulated mouse macrophages 664, 665, 666, 667, 668, 669, 670, 672, 680. NO production inhibitor, stimulated macrophages 728, 729, 854, 855, 856, 857, 858.

P Phospholipase A inhibitor 532. Phytotoxin 433. PKC activator 370, 406, 511, 512, 513, 514, 534, 535, 536. PLA inhibitor 1076, 1077, 1078. PLA2 inhibitor 205, 517, 521, 823, 844, 914, 1077, 1078. Plant growth regulator 213. Potent convulsant drug 285. Precursor to the cembrane lactone, found in various soft coral 731. Predator deterrent 160, 210. Protectant of mollusc 404, 405. Protein Mcl-1 inhibitor, Mcl-1/Bak fluorescence resonance energy transfer assay 175. Protein synthesis inhibitor, fungi 140. Putative biogenetic precursor of raikovenal 58. R Reducer of accumulation of iNOS 630. Reducer of COX-2 expression, hmn colon adenocarcinoma cells and murine macrophage RAW264.7 cells 974, 975. Reduces COX-2 expression 848. Reduces level of iNOS 192, 848, 849, 850, 853. Relaxant 358. Repels and are Toxic, prosobranch Drupella fragum 908, 910. Reverses MDR of KB-3-1 977, 978, 979. Reverses MDR of KB-C2 977, 978, 979. RT inhibitor 133. S Sedative 39. Seems to be useful as a measure to counter red tide 409. Skin irritant 2. Smooth muscle contractant 420. Smooth muscle contractor 433. Smooth muscle relaxant 39. Spasmolytic 375, 408, 421, 422.

Index 5 Compound Pharmacological Activity Index

Sporogenic 193. Strong nonselective against almost all of NCI panel cell lines 762. Superoxide anion generator 195. Superoxide inhibitor 828. T Toxic 52, 55, 81, 225, 392, 1120. Toxic, brine shrimp 37, 46, 57, 87, 88, 198, 233, 238, 251, 255, 261, 267, 349, 355, 361, 362, 366, 367, 504, 620, 714, 803, 825, 826, 842, 904, 915, 952, 984, 985, 986, 996, 1111, 1112, 1113, 1114. Toxic, brine shrimp Artemia salina 629. Toxic, brine shrimp lethality 662. Toxic, developing eggs of sea urchin Strongylocentrotus 477. Toxic, fish 842.

(The End of HAMNP Volume 1)

453

Toxic, grasshoppers 981. Toxic, implicated in hmn food poisoning from cooked oysters from whose shells had not been removed 391. Toxic, many organisms 80. Toxic, marine fish Pomacentrus coeruleus 60, 61. Toxic, marine organisms 369. Toxic, mosquito fish Gambusia affinis 154. Toxic, to copepod larvae 1127. Toxin, necrotic to soft corals 43. Tubulin polymerisation induction inhibitor 846. Tumorigenesis inhibitor 715. Tumour promoter 370, 511, 512, 534, 536. Tyrosine metabolism and 5-aminolevulinic acid dehydrase inhibitor 392.