Fortschritte der Chemie organischer Naturstoffe. Progress in the Chemistry of Organic Natural Products. Founded by L. Zechmeister

Transcription

1

2

3 Fortschritte der Chemie organischer Naturstoffe Progress in the Chemistry of Organic Natural Products Founded by L. Zechmeister Editors: A. D. Kinghorn, Columbus, OH H. Falk, Linz J. Kobayashi, Sapporo Honorary Editor: W. Herz, Tallahassee, FL Editorial Board: V. M. Dirsch, Vienna S. Gibbons, London N. H. Oberlies, Greensboro, NC Y. Ye, Shanghai

4 91 Fortschritte der Chemie organischer Naturstoffe Progress in the Chemistry of Organic Natural Products Naturally Occurring Organohalogen Compounds A Comprehensive Update Author: G. W. Gribble SpringerWienNewYork

5 Prof. A. Douglas Kinghorn, College of Pharmacy, Ohio State University, Columbus, OH, USA em. Univ.-Prof. Dr. H. Falk, Institut für Organische Chemie, Johannes-Kepler-Universität, Linz, Austria Prof. Dr. J. Kobayashi, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machines or similar means, and storage in data banks. # 2010 Springer-Verlag/Wien Printed in Germany SpringerWienNewYork is a part of Springer Science þ Business Media springer.at Product Liability: The publisher can give no guarantee for the information contained in this book. This also refers to that on drug dosage and application thereof. In each individual case the respective user must check the accuracy of the information given by consulting other pharmaceutical literature. The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Cover photos: Both photos were taken by Professor Joseph R. Pawlik, University of North Carolina, Wilmington, Center for Marine Science Wilmington, NC 28409, USA. Sponge on left: Agelas clathrodes. Sponge on right: Aplysina archeri. Photos taken on coral reefs, m depth, Bahamas Islands. Library of Congress Catalog Card Number Typesetting: SPI, Chennai Printed on acid-free and chlorine-free bleached paper SPIN: With 41 coloured Figures ISSN ISBN e-isbn DOI / SpringerWienNewYork

6 Dedicated to the memory of my mother, Jane Adena Gribble, v

7 Brief CV Gordon W. Gribble Gordon W. Gribble is a native of San Francisco, California, and completed his undergraduate education at the University of California at Berkeley, in He earned a Ph.D. in organic chemistry at the University of Oregon, in Following a Postdoctoral Fellowship at the University of California, Los Angeles, he joined the faculty of Dartmouth College, in 1968, where has been Full Professor of Chemistry since He served as Department Chair from 1988 to In 2005, he was named to the newly endowed Chair as The Dartmouth Professor of Chemistry. Dr. Gribble has published 320 papers in natural product synthesis, synthetic methodology, heterocyclic chemistry, natural organohalogen compounds, and synthetic triterpenoids. Since 1995, he has coedited the annual series Progress in Heterocyclic Chemistry, and the 2nd edition of Palladium in Heterocyclic Chemistry, coauthored with Jack Li, was published in Dr. Gribble has had a long-standing interest in organic chemical toxicity, chemical carcinogenesis, environmental chemistry, and naturally occurring organohalogen compounds. As an award winning home winemaker for the past 30 years, he has a strong interest in the chemistry of wine and winemaking. vii

8 Acknowledgements The author is grateful to Gettysburg College for a sabbatical leave in Gettysburg, Pennsylvania, during when the majority of this review was prepared, and is especially appreciative to the late Professor Richard Moore (University of Hawai 0 i) who suggested Fortschritte der Chemie organischer Naturstoffe as a forum for this review and the preceding one in Volume 68. A special thanks goes to Ms. Wendy Berryman who typed the manuscript and drew all of the structures, and to Professors Heinz Falk and Douglas Kinghorn for their enormous assistance with the preparation of the manuscript. The author also acknowledges the inspiration and encouragement by three late outstanding scientists and pioneers in the war against chemophobia and the public s irrational fear of chlorine: Professors Gordon Edwards (San Jose State University), Fredrick Stare (Harvard School of Public Health), and Thomas Jukes (University of California, Berkeley). A special personal acknowledgement goes to the late Mr. Jack Grant for his friendship during my time in Gettysburg. ix

9 Contents List of Contributors... xv 1 Introduction Origins Marine Environment Terrestrial Environment Extraterrestrial Environment Occurrence Simple Alkanes Chloromethane Dichloromethane Trichloromethane Tetrachloromethane (Carbon Tetrachloride) Bromomethane Other Simple Bromoalkanes Mixed Bromochloromethanes Iodomethanes Other Simple Iodoalkanes Mixed Iodomethanes Simple Alkenes Simple Alkynes Simple Organofluorines Other Simple Organochlorines Simple Functionalized Acyclic Organohalogens Simple Functionalized Cyclic Organohalogens Cyclopentanes Cyclitols and Benzoquinones xi

10 xii Contents 3.4 Terpenes Monoterpenes Sesquiterpenes Diterpenes Higher Terpenes Steroids Marine Nonterpenes: C 15 Acetogenins Iridoids Lipids and Fatty Acids Fluorine-Containing Carboxylic Acids Prostaglandins Furanones Amino Acids and Peptides Alkaloids Heterocycles Pyrroles Indoles Carbazoles Indolocarbazoles Carbolines Quinolines and Other Nitrogen Heterocycles Benzofurans and Related Compounds Pyrones and Chromones Coumarins and Isocoumarins Flavones and Isoflavones Carbohydrates Polyacetylenes Terrestrial Polyacetylenes and Derived Thiophenes Marine Polyacetylenes Enediynes Macrolides and Polyethers Naphthoquinones, Higher Quinones, and Related Compounds Tetracyclines Aromatics Simple Phenols Terrestrial Marine Complex Phenols Diphenylmethanes and Related Compounds Diphenyl Ethers Tyrosines Depsides Depsidones Xanthones Anthraquinones and Related Compounds

11 Contents xiii Griseofulvin and Related Compounds Miscellaneous Fungal Metabolites and Other Complex Phenols Glycopeptides Orthosomycins Dioxins and Dibenzofurans Humic Acids Biohalogenation Introduction Chloroperoxidase Bromoperoxidase Halogenases, Other Haloperoxidases and Peroxidases Myeloperoxidase Abiotic Processes Biofluorination Biosynthesis Biodegradation Natural Function Significance Outlook References Author Index Subject Index Listed in PubMed

12 List of Contributors Gribble, Prof. Dr. G. W., Dartmouth College, Department of Chemistry, 6128 Burke Laboratory, Hanover, NH 03755, USA xv

13 1 Introduction The previous survey documented 2,448 naturally occurring organohalogen compounds, both biogenic and abiotic (1). In the intervening years an additional 2,266 compounds have been identified from a myriad of natural sources, which include chlorine-, bromine-, iodine-, and fluorine-containing organic compounds. The organization herein follows that used earlier so as to provide continuity. Numerous reviews covering natural organohalogens, both very general and highly specialized, have appeared since 1994 (2 72). Others will be cited in the appropriate section. While the furor over chlorine has abated to some extent, there remains an underlying chlorophobia an irrational fear of chlorine and organochlorine compounds. It is hoped that the present review along with the references cited herein will help to balance the need to regulate persistent organic organohalogen pollutants (e.g., POPs ) against the clearly demonstrated important role of organohalogens both natural and anthropogenic in our society and in the environment. G.W. Gribble, Naturally Occurring Organohalogen Compounds A Comprehensive Update, Progress in the Chemistry of Organic Natural Products, Vol. 91, DOI / _1, # Springer-Verlag/Wien

14 2 Origins The ubiquitous abundance of the four halides (Table 2.1) has resulted in the evolution of organohalogens in all regions of our earth, both biogenic and abiotic (73 77). 2.1 Marine Environment As will be seen, most naturally occurring organohalogen compounds are unique to individual marine organisms and are not widely dispersed in the environment. However, the more volatile haloalkanes, which have several marine sources, are important contributors to the atmosphere. The salinity of Earth s early ocean was probably twice that of the present value (77), and sea-salt spray is the major atmospheric source of reactive halogens (Cl 2,Br 2, BrCl, HOCl, HOBr) that are subsequently converted to chlorine oxide and bromine oxide. This atmosphere chemistry is exceedingly complex and beyond the scope of this review (78 85). The formation of reactive chlorine and bromine in sea-salt aerosols, for which there is compelling evidence, may explain the low ozone concentrations that are often observed above the oceans (86 94). The importance of bromine oxide to both tropospheric and stratospheric bromine-ozone chemistry has been stressed (95 100). Not surprising is the observation of similar bromine oxide-ozone interactions over the Dead Sea (101), and both bromine oxide and chlorine oxide chemical reactions with ozone over the Great Salt Lake (102), with concomitant ozone depletion in both areas. Although less studied, iodine in the marine boundary layer is well known and can involve the photolysis of marine biogenic organoiodine compounds (103, 104). Moreover, it appears that the global aerosol load has a major contribution from marine organohalogen aerosols with the inevitable formation of reactive halogens (105). As abundantly illustrated in the first survey, marine organisms produce and sequester an enormous number of organohalogens. It is estimated that more than 15,000 marine natural products of all types have been described (106). This author G.W. Gribble, Naturally Occurring Organohalogen Compounds A Comprehensive Update, Progress in the Chemistry of Organic Natural Products, Vol. 91, DOI / _2, # Springer-Verlag/Wien

15 4 2 Origins Table 2.1 Distribution of halides/mg kg 1 in the environment Halide Oceans (73, 74) Sedimentary rocks (66, 74) Fungi (75) Wood pulp (218) Plants (74, 76) Cl 19, ,000 Br I F has determined from the published literature ( ) that 15 20% of all newly discovered marine natural products are organohalogens (107). Given the salinity of the world s oceans, which occupy more than 70% of the earth s surface and over 90% of the volume of the crust (108), it is not surprising that organohalogens are plentiful in the 500,000 estimated species of marine organisms spread over 30 phyla (109). This figure includes 100,000 marine invertebrates (110), 80,000 molluscs (111), 15,000 sponges (112), and 4,000 species of bryozoa (moss animals) (113). Perhaps due to their accessibility (and visibility!), sponges the simplest and earliest multicellular organisms that evolved about one billion years ago (114) have been widely examined for their chemical content, and new sponge species are still being discovered (115). However, to acquire significant quantities of biologically active sponge metabolites, it is necessary to develop farming methods (116, 117) or to employ cell culture and gene cluster tactics (118). A major sponge research area has been to explore the now well-established spongebacteria symbiosis ( ). Such studies of sponges include Aplysina cavernicola ( ), Aplysina aerophoba ( ), Theonella swinhoei (128), Rhopaloeides odorabile (129, 130), and Xestospongia muta and X. testudinaria (131), all of which have associated active bacterial communities that may produce the metabolite. Even older than sponges are cyanobacteria (blue-green algae, Fig. 2.1), which date back 2.8 billion years (132). As will be seen in Chap. 3 (Occurrence), the 2,000 species of cyanobacteria produce a multitude of organohalogen and other metabolites ( ), which are often highly toxic to humans ( ). The cyanobacterium Oscillatoria spongeliae is a common symbiont of the sponges Dysidea herbacea and Dysidea granulosa (Fig. 2.2) ( ), but the actual producer of the organohalogen metabolites remains uncertain. As will be presented in Chap. 3 (Occurrence), other marine organisms such as molluscs (145), sea hares (146), mussels (147), bryozoans (148), tunicates, and soft corals (149) produce a myriad of organohalogen metabolites. Interestingly, symbiotic bacteria can also be associated with these organisms (123). Marine phytoplankton (150) and macroalgae (151, 152) are rich sources of organohalogens, particularly volatile haloalkanes. Two relatively new areas for ocean exploration are marine bacteria and fungi (108, , 178). Finally, as more remote and deeper regions of the oceans are explored, new marine species are being discovered; for example, the new genus, Osedax, of marine worms (156).