International Symposium on Marine Natural Products. Plenary Lectures Presented at the International Symposium on Marine Natural Products, Aberdeen, Scotland, 8–11 September 1975

45 Pages·1976·1.255 MB·English

by  R. H. Thomson (Eds.)

Organizing Committee
Chairman &
Symposium Editor: R. H. Thomson
Members: J. F. Gibson
J. R. Lewis
O. C. Musgrave
A. B. Turner
International Union of Pure and Applied Chemistry
(Organic Chemistry Division)
in conjunction with
The Chemical Society
Perkin Division
International Symposium on
Marine Natural Products
Plenary lectures presented at the
International Symposium on Marine
Natural Products, Aberdeen,
Scotland, 8-11 September 1975
Symposium Editor:
R. H. Thomson
University of Aberdeen, Scotland
PERGAMON PRESS
OXFORD NEW YORK TORONTO · SYDNEY PARIS FRANKFURT
U.K. Pergamon Press Ltd., Headington Hill Hall,
Oxford OX3 0BW, England
U.S.A. Pergamon Press Inc., Maxwell House, Fairview Park,
Elmsford, New York 10523, U.S.A.
CANADA Pergamon of Canada Ltd., 75 The East Mall,
Toronto, Ontario, Canada
AUSTRALIA Pergamon Press (Aust.) Pty. Ltd., 19a Boundary Street,
Rushcutters Bay, N.S.W. 2011, Australia
FRANCE Pergamon Press SARL, 24 rue des Ecoles,
75240 Paris, Cedex 05, France
WEST GERMANY Pergamon Press GmbH, 6242 Kronberg Taunus,
Pferdstrasse 1, Frankfurt-am-Main, West Germany
Copyright © 1976 International Union of Pure and Applied Chemistry
Ail Rights Reserved. No part of this publication may be
reproduced, stored in a retrieval system or transmitted in
any form or by any means: electronic, electrostatic,
magnetic tape, mechanical, photocopying, recording or
otherwise, without permission in writing from the
publishers
The contents of this book appear in
Pure and Applied Chemistry, Vol. 48, No. 1 (1976)
Printed in Great Britain by A. Wheaton & Co., Exeter
ISBN 0 08 021242 5
Pure & Appl. Chem., Vol. 48, pp. 1-6. Pergamon Press, 1976. Printed in Great Britain.
SOME RECENT DEVELOPMENTS IN THE
CHEMISTRY OF ALCYONACEANSt
BERNARD TURSCH
Collectif de Bio-Ecologie, Université Libre de Bruxelles, Brussels, Belgium
Abstract—Sesquiterpenes, diterpenes and sterols found in Alcyonaceans are briefly reviewed. Their biogenetical
origin, their distribution and their biological significance are discussed.
Coral reefs are scattered in tropical shallow waters and their bulky, fleshy colonies yield large proportions of
covering about 190,000,000 km2. It has been estimated that extractable organic matter. Indeed, alcyonaceans seem to
the area of the reefs themselves is comparable to that of be the largest single contributors to the biomass of many
all cultivated land on earth.1,2 The primary productivity of Indo-Pacific reefs, a view supported by recent careful reef
the reefs varies from 1500 to 3500 g of carbon/m2/yr: this transect studies.6
is a hundred times more than that of the surrounding seas In addition to their pondéral importance, Octocorallia
and eight times more than that of the most productive are remarkable by their ability to ward off algal and
regions of temperate seas.3,4 A striking characteristic of microbial growth and to prevent the settlement of
the reefs is their diversity: they contain many more larvae.78 Alcyonaceans are submitted only to negligible
species than any other marine biotope. Coral reefs thus grazing by large predators and all crude soft coral extracts
constitute a potentially very important natural asset. They tested so far were indeed highly unpalatable to a variety
are still practically untapped to this day but it can be of reef fishes. The existence of such a set of diversified
safely predicted that they will be systematically exploited and effective chemical defenses having been surmised
in years to come. It can only be hoped that massive many years ago, it is not surprising that Octocorals have
exploitation will be delayed until reliable conservation been one of the first marine groups to be the target of
rules are worked out through progress in reef ecology, a systematical chemical scrutiny.
very complex field which is still in its prime infancy. Gorgonians, being within easy reach of well-established
The reef environment ideally fulfills the needs of the chemical laboratories, were naturally studied first. Within
marine natural products chemist. A maximum diversity of a few years they yielded a rich crop of novel and
species provides the opportunity for practically unlimited interesting compounds9 including sterols,10 prostaglan-
chemical prospection. Furthermore, since reefs are dins,11 butenolides,12 sesquiterpenoid hydrocarbons,13
necessarily located in clear, shallow waters, collecting can cembranolide9,14 and other15 diterpenoids. Since a very
generally be effected without the need of very sophisti- large number of gorgonian species still remain to be
cated equipment. These conditions certainly favour the investigated one can assume that these impressive results,
pursuit of classical activities such as detection and study in great part due to the group of the University of
of potentially useful physiologically active compounds or Oklahoma, are yet a hors d'oeuvre for other exciting
the more academic search for structural novelties. findings to come.
Furthermore one should emphasize that many reef Alcyonaceans are rather closely related to the Gorgona-
species seem to be strongly interdependent: the study of ceans and one could speculate that they would possibly
chemical interactions between these species constitutes a yield their share of interesting molecules. The first results
most challenging field of investigations. have not been discouraging and it is the purpose of this
Reefs are built by hermatypic corals (mainly Coelen- paper to report on the current situation in this field. In
terata, Hexacorallia) and calcareous algae. These provide order to review present events it has been deemed
the ecological niches that are occupied by a multitude of necessary to mention a few compounds whose structures,
reef dweller species, forming one of the richest and most although quite convincing, have not yet been established
complex living communities on the planet. The reef- by unambiguous proof.
building hermatypic corals generally dominate in volume
and in numbers but not necessarily in biomass, calcium SESQUITERPENES
carbonate being by very far their main production. Africanol, Ci H 60, has been isolated from Lemnalia
5 2
Prominent amongst the sessile reef-dwellers is another africana collected at the island of Tanimbar, Southern
group of coelenterates, the subclass Octocorallia. The Moluccas. It is the first representative of a novel
most conspicuous of these are the familiar gorgonians or sesquiterpene skeleton. Its structure (1) and absolute
sea-fans (Order Gorgonacea), of world-wide distribution configuration were established by X-ray diffraction
but whose metropolis is the Caribbean region,5 and the analysis.16 Africanol has also been isolated from the
alcyonaceans or soft corals (Order Alcyonacea) which are related species Lemnalia nitida, also from Tanimbar.
abundant in the Indo-Pacific region. In contrast to the
hermatypic corals, possessing massive inorganic skeletons
surrounded by a thin layer of living tissues, alcyonaceans
have a skeleton consisting of minute calcareous spicules,
tPaper XV in the series: Chemical Studies of Marine
Invertebrates. For paper XIV, see Ref. 21.
1
2 BERNARD TURSCH
Lamnalia carnosa, collected at Leti Island, Southern Another yet undescribed sesquiterpene has been
Moluccas, yielded the novel sesquiterpene lemnacarnol, obtained from the Xeniid Cespitularia viridis, collected in
C15H24O3, whose structure (2) and absolute configuration the Seychelles Islands. It is an isomer of africanol (1) and
were also determined by X-ray diffraction.17 Its carbon also contains a three membered carbon ring.
skeleton is antipodal to that of the known plant
sesquiterpene nardosinone (3),18 thus confirming the re- DITERPENES
markable observation that "each of the sesquiterpenes Schmitz, Vanderah and Ciereszko22 have reported the
isolated from marine coelenterates is the optical antipode structures of nephteno (15) and epoxynephtenol acetate
of the form found, where known, in terrestrial plants".9 (16) obtained from a Nephtea sp. collected at Eniwetok.
Paralemnalia thyrsoldes from Tanimbar afforded two
closely related compounds, 2-desoxylemnacarnol,
C15H24O2 (4) and 2-desoxy-12-oxo-lemnacarnol, C15H22O3
(5) (also found in Lemnalia africana from Tanimbar). The
structures of these compounds rest on chemical and
spectral evidence. Compounds (4 and 5), upon treatment
with lithium-aluminium hydride afford the same mixture of
epimeric diols (6).19
The cembranolide diterpene sarcophine (17) has been
isolated by Israeli workers from Sarcophytum glaucum,
collected in the Red Sea. Its structure was established by
OH X-ray diffraction analysis.23 Sarcophine is a toxic material
1 and its physiological action has been reported.24 Mainly
on the basis of spectral data, the same research group
reported structures (18-23) for six additional diterpenes
isolated from the same source, structure (23) being
Capnella imbricata contains an interesting mixture of tentative.25
polyhydroxylated sesquiterpenoids, all based upon the
novel skeleton capnellane (7). The structure of Δ9(12-)
capnellene-3ß,8ß,10a-triol (8) was deduced from chemi-
cal and spectral evidence. It was independently estab-
lished by single-crystal X-ray diffraction analysis, which
also gave its stereochemistry and absolute configuration.20
The structure proof of its naturally occurring 3-acetate (9)
was quite straightforward.
Nephtenol (15) has also been obtained from Litophyton
viridis, collected at Leti Island, Southern Moluccas. In
The structures of A9(12-)capnellene-5a,80,lOa-triol (10) this instance, its absolute configuration was determined: it
A^-capnellene-SftlOa-diol (11) and A9(,2-)capnellene- is (-)-nephtenol, depicted in structure (24). It is accom-
2£8/3,10a-triol (12) were deduced mainly from spectral panied by 2-hydroxynephtenol C20H34O2 (25), whose
evidence and confirmed by chemical correlation.21 The structure rests on chemical and spectral evidence.26
main lines of the correlation were the obtention of the key
intermediate (13) in seven steps from compound (8), four
steps from compound (11) and seven steps from
compound (10). A tetrol (14), whose spectral data indicate
it is compound (8) with an additional primary hydroxyl
group has also been isolated. Its structure has not yet been
completely demonstrated. Our samples of Capnella
imbricata come from the islands of Lakor, Masela, 25
Sermata, Tanimbar and Leti, all in the Indo-Malay
archipelago, and from Laing Island, Papua-New Guinea. Lobophytum cristagalli, also from Leti Island, yielded
All contain compound (11) but the presence and relative lobophytolide C20H28O3 (26), whose structure was estab-
amounts of the other capnellane sesquiterpenoids have lished by chemical and spectral data. Its stereochemistry
been found to vary considerably from population to was obtained by X-ray diffraction analysis.27
population. Colonies of Sarcophyton trocheliophorum collected in
- I H 0Η<ΪΗ2 · I H 2
OHf Ι H 0H„
OH
10
Some recent developments in the chemistry of alcyonaceans 3
the Seychelles Islands contained the diterpene
trocheliophorol C20H34O2 (27). Its structure was deduced
from chemical and spectral evidence. This compound was
not detected in specimens collected at Leti (Indonesia),
which afforded two other compounds, sarcophytoxide OAc AcO- -OAc
C20H30O2 (28) (stereoisomer of (20 and 21)) and isosar-
cophytoxide C20H30O2 (29).28 The structure of these Ο
compounds still await unambiguous demonstration. OAc
36
Only preliminary data are yet available for lem-
nalialoside C26H42O6, obtained from Lemnalia digitata,
collected at Tanimbar Kei, Indonesia. Hydrolysis indi-
cates it consists of an aldehyde C20H32O attached to
D-glucose by a rather unusual ketal linkage. NMR
spectra of lemnalialoside and its derivatives indicate
26
it is a 0-glucoside with the partial structure (37). The
aldehyde aglycone contains two double bonds, each
substituted by a methyl group and is thus necessarily
bicyclic. Lemnalialoside is the first example of an
alcyonacean diterpene that does not belong to the
cembrane group.33
28 29
CH-0-ÇH-CH Çl8H30
A series of close related cembranolides was isolated
from Sinularia flexibilis collected at the islands of Leti
and Kissar, in the Southern Moluccas. The structure of
sinulariolide C20H30O4 (30) was obtained by chemical
degradation and spectral data. It was independently
established by X-ray diffraction analysis, which also
yielded its stereochemistry and absolute configuration.29
Sinulariolide is accompanied by 5-dehydrosinulariode
STEROLS
(31), 5-episinulariolide acetate (32) and lOf-
All alcyonaceans studied so far contain more or less
hydroxy-sinulariolide (33). A diterpene hydrocarbon that
complex mixtures of monohydroxysterols such as choles-
on the basis of its i.r., NMR and mass spectra appears to be
terol, 24-methylcholesterol, 24-methylenecholesterol,
cembrene-A (34)30 has also been isolated from the same
brassicasterol, gorgosterol and other common marine
source.31
sterols. They are often accompanied by minor compounds
amongst which one could expect novel structures to be
found. For instance 23,24-dimethylcholesta-5,22-dien-3ß-
ol (38) has recently been obtained by Japanese workers
from Sarcophyton elegans.34
Di- and polyhydroxysterols are quite frequently en-
countered in soft corals, 25-hydroxy-24£-methyl-
cholesterol (39) was isolated from Sinularia may/, col-
lected at Nias Island, near Sumatra.35
Another dihydroxysterol is 12a-hydroxy-24-
methylenecholesterol (40) obtained from Litophyton
viridis, collected at Leti.36
34
The highly oxygenated diterpene crassolide C26H34O9
has been isolated from Lobophytum crassum, collected at
Leti Island. Its partial structure (35) has been established
mainly by NMR decoupling experiments. All data in our
possession point at structure (36) for crassolide.32 40
4 BERNARD TURSCH
Two triols, 24£-methylcholestane-3ß,5a,6ß-triol (41) Some genera, like Lemnalia, contain representatives
and 24-methylenecholestane-3/3,5a,6/3-triol (42), each possessing either sesquiterpenes or diterpenes, but these
accompanied by its 6-monoacetate, were isolated from two families of terpenoids have never yet been encoun-
Sinularia dissecta, collected at Leti Island. Their struc- tered together in the same species. Sesquiterpenes have
tures have been established mainly by chemical correla- been isolated only from the families Nephtheidae and
tion.37 These compounds are closely related to 24f- Xeniidae. These data should be interpreted only as
methylcholestane-3j8,5a,6jß,25-tetrol 25-monoacetate (43), preliminary indications since less than a hundred species
previously obtained from Sarcophyton elegans (collected have been subjected even to preliminary evaluation.
in the Seychelles Islands) and whose structure was Furthermore it is felt that only some of the most stable
demonstrated by chemical and spectral arguments.38 and most obvious compounds have been so far isolated.
A still further stage of sterol oxidation was found in Many of the alcyonacean terpenoids are notoriously
lobosterol (44) obtained from Lobophytum pauciflorwn, unstable and number of promising and abundant com-
collected in the Seychelles. Its structure and absolute pounds have vanished between routine TLC screening on
configuration were established by X-ray diffraction the reef and reception of the samples in the laboratory.
analysis.39 Obvious artefacts have been isolated in some instances;
they have not been mentioned in this text.
ORIGIN AND IMPLICATIONS
Like many coelenterates (in particular hermatypic
corals, gorgonians and sea-anemones) most reef-dwelling
alcyonaceans live in symbiosis with intracellular di-
noflagellate algae known as zooxanthellae. This associa-
tion is not passive and the existence of important
chemical exchanges between the partners have been
demonstrated.40 Zooxanthellae play a prominent part in
the ecology of a coral reef2,41 and it appears that it is the
availability of light that restricts the reefs to clear, shallow
waters. At the depth limit, called compensation depth,
illumination is such that the photosynthetic activity of the
algae exactly compensates their respiratory activity.42 The
molecular aspects of such a symbiosis certainly constitute
a most tantalizing field of research.
A growing body of evidence indicates that the
xanthellae (alone or in conjunction with the coelenterate
tissues) are responsible for the synthesis of the terpenoids
encountered in the Alcyonaria.943 Attempts to detect
terpenoids in alcyonaceans that are devoid of xanthellae
(such as the European Alcyonium digitatum) have
consistently failed. The gorgonian Eunicella stricta which
afforded the diterpene eunicelline15 has a deep water form
Eunicella stncta aphyta that is devoid of zooxanthellae.44
Very careful examination of the form aphyta failed to
44 detect the presence of eunicelline, although the chemical
content of both forms appeared otherwise quite similar.45
Alcyonaceans certainly constitute a rich source for If, as it would seem, xanthellae are indispensable for
polyhydroxysterols: many more compounds have been the production of terpenoids, then the study of these
isolated and are at present under study. compounds might be quite irrelevant to the taxomomy of
alcyonaceans but most important for the systematics of
DISTRIBUTION the symbiotic zooxanthellae themselves, a field which is
So far, the occurrence of terpenoids in various today practically non-existent. Since the very existence of
alcyonacean genera can be summarized as in Table 1. the coral reef ecosystem appears to rest on the association
Table 1. Distribution of terpenoids in alcyonaceans
Sesquiterpenes Diterpenes Polyhydroxysterols
Fam. Alcyoniidae
gen. Lobophytum + +
Sarcophyton + +
Sinularia + +
Fam. Nephtheidae
gen. Capnella +
Lemnalia + +
Litophyton + +
Nephtea +
Paralemnalia +
Fam. Xeniidae
gen. Cespitularia +
Some recent developments in the chemistry of alcyonaceans 5
of xanthellae with coelenterate hosts, several questions 5281, (1970); F. J. Schmitz and T. Pattabhiraman, Ibid. 92, 6073
do immediately come to the mind. Are there one or many (1970); E. L. Enwall, D. Van Der Helm, I. Nan Hsu, T.
species of xanthellae? If many, are the associations Pattabhiraman, F. J. Schmitz, R. L. Spraggins and A. J.
specific? If specific, are the associations exclusive? Weinheimer, Chem. Comm. 215 (1972).
"A. J. Weinheimer and R. L. Spraggins, Tetrahedron Lett. 5185
Unless one postulates a quite unprecedented biochemical
(1969); G. L. Bundy, E. G. Daniels, F. H. Lincoln and J. E. Pike,
plasticity, the great variety of terpenoids encountered so
/. Am. chem. Soc. 94, 2124 (1972); W. P. Schneider, R. D.
far pleads in favour of the existence of numerous species
Hamilton and L. E. Rhuland, /. Am. chem. Soc. 94, 2122 (1972);
of xanthellae. Furthermore, the regularity of occurrence R. J. Light and B. Samuelsson, Europ. J. Biochem. 28,232 (1972).
of given compounds in given alcyonacean species would ,2F. J. Schmitz, Κ. W. Kraus, L. S. Ciereszko, D. H. Sifford and A.
indicate that the associations are specific, in agreement J. Weinheimer, Tetrahedron Lett. 97 (1966); F. J. Schmitz, E. D.
with the general principle that "two species with the same Lorance and L. S. Ciereszko, J. Org. Chem. 34,1989 (1969); F. J.
ecology cannot coexist".46 Schmitz and E. D. Lorance, Ibid. 36, 719 (1971).
13
It has been commonly observed that alcyonaceans of A. J. Weinheimer and P. H. Washecheck, Tetrahedron Lett.
3315 (1969); A. J. Weinheimer, P. H. Washecheck, D. Van Der
the same species but from different localities contain
Helm and B. Hossain, Chem. Comm. 1070 (1968); A. J.
different (but closely related) terpenoids. A compound
Weinheimer, W. W. Youngblood, P. H. Washecheck, T. Κ. B.
can even be dominant in a given population and con- Karns and L. S. Ciereszko, Tetrahedron Lett. 497 (1971); P. W.
spicuously absent from another. This could indicate Jeffs and L. T. Lytle, Lloydia, 37(2), 315 (1974).
that the same coelenterate host might accomodate several ,4A. J. Weinheimer, R. E. Middlebrook, J. O. Bledsoe, W. E.
related varieties of xanthellae and that the associations Marsico and T. Κ. B. Karns, Chem. Comm. 384 (1968); M. B.
are not necessarily exclusive. In the absence of firm Hossain, A. F. Nicholas and D. Van Der Helm, Chem. Comm.
premises, these views should yet be regarded as strictly 385 (1968); M. B. Hossain and D. Van Der Helm, /. Am. chem. Soc.
90, 6607 (1968).
speculative. I5
0. Kennard, D. G. Watson, L. Riva Di Sanseverino, Β. Tursch,
R. Bosmans and C. Djerassi, Tetrahedron Lett. 2879 (1968).
BIOLOGICAL SIGNIFICANCE I6
B. Tursch, J. C. Braekman, D. Daloze, P. Fritz, A. Kelecom, R.
The obvious protection of Alcyonaceans towards large Karlsson and D. Losman, Tetrahedron Lett. 9, 747 (1974).
predators such as fish can be justified by the presence of 17B. Tursch, M. Colin, D. Daloze, D. Losman and R. Karlsson,
tGoaxmicb utseiarp enaoffiidnsi.s Thhase bLeDen5 0 reopf orstaedrc otpoh inbee (31 7m)g /1fo.r24 ,8GB.u lRl. üSckoecr., CTheitmra. heBderlogn. 8L4e, t8t.1 (31691755 )(.1 968).
,9
Lethality tests on Lebistes reticulatus have shown that B. Tursch, P. Georget, J. C. Braekman and D. Daloze,
africanol (1) has a LD of 4 mg/1, crassolide (36) a LD Unpublished data.
50 50 20
47 M. Kaisin, Y. M. Sheikh, L. J. Durham, C. Djerassi, B. Tursch,
of 7 mg/1 and lobophytolide (26) a LD of 12 mg/1. Since
50 D. Daloze, J. C. Braekman, D. Losman and R. Karlsson,
feeding deterrent action would probably take place below
Tetrahedron Lett. (26) 2239 (1974).
lethal concentrations, alcyonaceans could be effectively 2,
Y. M. Sheikh, G. Singy, M. Kaisin, H. Eggert, C. Djerassi, B.
protected by terpenoids occurring at concentrations
Tursch, D. Daloze, J. C. Braekman, To be published.
below 0.001% and thus generally escaping routine 22F. J. Schmitz, D. J. Vanderah and L. S. Ciereszko, Chem. Comm.
isolation techniques. 407 (1974).
23
No acute toxicity could be established for some J. Bernstein, U. Schmeuli, E. Zadock, Y. Kashman and I.
abundant terpenoids such as the capnellenes (10 and 11), Neeman, Tetrahedron 30, 2817 (1974).
24
sinulariolide (30) and lemnalialoside (37). In contrast, I. Neeman, L. Fishelson and Y. Kashman, Toxicon 12, 593
(1974).
these compounds have been shown to be powerful 25
Y. Kashman, E. Zadock and I. Neeman, Tetrahedron 30, 3615
inhibitors of algal growth, minute concentrations com-
(1974).
pletely preventing the growth of the unicellular algae 26
B. Tursch, J. C. Braekman and D. Daloze, Bull. Soc. Chim. Belg.
Chaetoceros septentrionalis, Asterionella japonica, 84 (7), 767 (1975).
Thalasioscira excentricus, Protocentrum micans and 27B. Tursch, J. C. Braekman, D. Daloze, M. Herin and R.
Amphidinium cart erae. The same activity was observed Karlsson, Tetrahedron Lett. 3769 (1974).
48 28
for africanol (l). It is tempting to speculate that such B. Tursch, P. Cornet, J. C. Braekman and D. Daloze,
compounds could be used to protect the specificity of the Unpublished data.
29
coelenterate-zooxanthellae associations. B. Tursch, J. C. Braekman, D. Daloze, M. Herin, R. Karlsson
and D. Losman, Tetrahedron 31, 129 (1975).
30
V. D. Patil, U. R. Nayar and Sukh Dev, Tetrahedron 29, 341
REFERENCES (1973).
3I
'J. V. Wells, Treatise on marine ecology and paleoecology (1957). B. Tursch and M. Herin, Unpublished data.
2 32
C. M. Yonge, The biology of ceral reefs, in: Advances in Marine B. Tursch, J. C. Braekman, D. Daloze and H. Dedeurwaerder,
Biology. Vol. 1 (1963). Unpublished data.
3
A. J. Kohn and P. Helfrich, Limnol. Oceanogr. 2, 241 (1957). "B. Tursch, J. C. Braekman, C. Charles, D. Daloze, M. Herin, A.
4
J. W. Kanwisher and S. A. Wainwright, Biol. Bull. 133, 378 Kelecom and M. Van Haelen, Unpublished data.
(1967). 34A. Kanazawa, S. Teshima, T. Ando and S. Tomita, Bull. Jap.
S
F. M. Bayer, The Shallow-Water Octocorallia of the West Indian Soc. Sei. Fish. 40(7), 729 (1974).
Region. The Hague (1961). 35J. P. Engelbrecht, Β. Tursch and C. Djerassi, Steroids 20(1), 121
6
H. Mergner and H. Schuhmacher, Helgoländer wiss. Meeresun- (1972).
ters. 26, 238 (1974). 36B. Tursch, J. C. Braekman, D. Daloze and P. Wautelet,
7
P. Burkholder and L. M. Burkholder, Science 127, 1173 (1958). Unpublished data.
8L. S. Ciereszko, Trans. N.Y. Acad. Sei. 24(2), 502 (1962). 37B. Tursch, M. Bortolotto, J. C. Braekman and D. Daloze,
9
L. S. Ciereszko and Τ. Κ. B. Karns. Comparative biochemistry Bull. Soc. Chim. Belg. 85, 27 (1976).
of coral reef coelenterates, in: Biology and Geology of Coral 38M. Moldowan, B. Tursch and C. Djerassi, Steroids 24(3), 387
Reefs. Vol. 2 (1), p. 183 (1973). (1974).
I0R. L. Hale, J. Leclercq, B. Tursch, C. Djerassi, R. A. Gross, A. J. 39C. Hootele, M. Kaisin, B. Tursch, D. Losman and R. Karlsson,
Weinheimer, K. Gupta and P. J. Scheuer, /. Am. chem. Soc. 92, To be published.
2179 (1970); N. C. Ling, R. L. Hale and C. Djerassi, Ibid. 92, 40L. Muscatine, Science, 156, 516 (1967); L. Muscatine and E.
6 BERNARD TURSCH
M
Cernichiari, Biol. Bull. 137, 506 (1969); D. Smith, L. Muscatine J. Theodor, Vie et Milieu 20 (3A), 635 (1969).
5
and D. Lewis, Biol. Rev. 44,17 (1969); C. Von Holt and M. Von *B. Tursch and M. Kaisin, Unpublished data.
t6
Holt, Comp. Biochem. Physiol. 24, 73, 83 (1968). A. Macfayden, Animal Ecology, p. 206. Pitman, New York
4,
T. F. Goreau, Ν. I. Goreau and C. M. Yonge, Biol. Bull. 141,247 (1963).
(1971). i7B. Tursch and M. Colin, Unpublished data.
42
R. H. Ryther, Deep Sea Res. 2, 134 (1954). *®Β. Tursch and C. Van Beveren, Unpublished data.
43
J. R. Rice, C. Papastephanou and D. Anderson, Biol. Bull. 138,
334 (1970).
Pure & Appl. Chem., Vol. 48, pp. 7-23. Pergamon Press, 1976. Printed in Great Britain.
NATURAL PRODUCT CHEMISTRY
OF THE MARINE SPONGES
L. MlNALE
Laboratorio per la Chimica di Molecole di Interesse Biologico del C.N.R.—Via Toiano n.2, Arco Felice, Napoli, Italy
Abstract—A systematic search for constituents of marine sponges has yielded over one hundred new compounds,
most of them with unique structural features. A broad survey of the field is presented and certain topics, particularly
those closely related to recent work done in our own laboratory on sesquiterpenoids, are discussed in more detail.
INTRODUCTION which may be considered as metabolites of 3,5-
In the context of the recent increased interest in the dibromotyrosine. Figure 1 lists their structures. The first
chemistry of marine organisms, the sponges, very primi- two members of the series were isolated from the
tive multicellular animals, have also received attention methanolic extracts of Verongiafistularis and V. caulifor-
leading to the discovery of many novel molecules. Since mis by Sharma and Burkholder.8"10 The failure to convert I
Bergmannes pioneering work1 on the fatty acids and into II by reacting with methanol under various conditions
sterols in sponges over a hundred different compounds allowed the authors to assume that the ketal II was a
have been isolated, mostly in the last 5-6 yr. genuine natural product and not an artifact generated
When I started to prepare this lecture I had the choice during the extraction. Recently Andersen and Faulkner11
of either presenting a summary review, or selecting only have isolated from the ethanolic extracts of an unde-
certain topics. It seemed to me best to choose the former. scribed species of Verongia the dienone I and the mixed
This would give a general picture of the sponge-derived ketal III, which latter was revealed to be a mixture of
natural products and should help to focus attention on the diastereoisomers (two methoxy signals in the 220 MHz
structural relationship between compounds isolated from NMR). This suggested that the ketal was not a natural
different species, and allow us to see if metabolites so far product and led the authors to propose that the dienone I,
isolated from sponges also occur in other marine phyla the dimethoxyketal II and the mixed ketal III may all be
and/or terrestrial organisms. derived from a single intermediate, such as an arene oxide
With your permission, I will attempt to discuss in more (XI), by 1,4 addition of water, methanol, or ethanol during
detail the very recent results from our own Laboratory, the extraction process. The recent work of Kasperek et
particularly those concerning sesquiterpenoids. α/.,12 showing that acid-catalyzed addition of methanol to
In this lecture, the known natural products from 1,4-dimethylbenzene oxide give 4 - methoxy - 1,4 - di-
sponges have been grouped in accordance with their methyl - 2,5 - cyclohexadienol, was quoted by the authors
probable biosynthetic origins, and I will discuss bromo- in support of their arguments.
compounds, terpenes, compounds of mixed biogenesis,
and sterols in that order. A brief mention of some
miscellaneous compounds will be also made. Fatty acids
H3CO OCH3 H3C0^ 0C2H5
lainsdh edp igomn etnhtes sea reto peixccsl usdinedc e atsh evye ryw elriett lela shta sr ebveieewn epdu bin- Τ τ Br^ί^ XΤ/B r BrNyX /Br
1968.23 HO CH2 HO CH2 HO CH2
I I 2 C 0 N H
C0NH2 C0NH2 ...
BROMO-COMPOUNDS (Sharma and Burkholder, 1967) (Andersen and Faulkner,1973)
About a hundred naturally occurring organobromo- Br
H B
compounds have been so far described, and only one of Br I
these was not isolated from a marine organism.4 Thus 0CNHE3 C-H2C °V0^UL^0CH3
these compounds, which belong to such diverse chemical
classes as phenols, pyrroles, indoles, sesquiterpenes, di-
terpenes, and polynuclear heterocycles, appear to be
characteristic of the marine environment. They have been
found especially in algae.5'6 Several brominated monoter-
penes, sesquiterpenes, and diterpenes have also been
extracted from the digestive gland of molluscs of the
genus Aplysia, but experiments revealed that the chemical
constituents of the digestive gland depended on the algal
diet of the individual Aplysia,7 and there now seems no
reason to doubt that the brominated terpenes from Ap-
lysia are derived from red algae such Laurencia, a
common food of the sea hare. So, besides the algae, the
richest source of bromo-compounds appears to be the
sponges.
Sponges of the family Verongidae have provided a x (Krejcarek et al ,1975 )
series of antibiotics and other closely related compounds Fig. 1. Tyrosine-derived bromo-compounds.
7