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Chemical analysis of the secondary metabolite pattern of the aeolid nudibranch Phyllodesmium magnum collected from the South China sea resulted in the isolation of eight sesquiterpenes, exhibiting very different structural features, which included one asteriscane (1), two africanane (2, 3), one elemane (4), two selinane (5, 6), and two furano- (7,8) sesquiterpenes. Among them, compound 1, a new molecule, represents the fourth example of a rare asteriscane skeleton from a natural source, and the seven known sesquiterpenes (2-8) are new for P. magnum. The occurrence of the metabolites possessed by Phyllodesmium guamensis supports recent chemecological studies that it preys on the soft coral Sinularia sp., and uses these dietary chemicals as its defensive weapon. (C) 2011 Elsevier Ltd. All rights reserved.

The diverse natural products found within sponges mediate many of their ecological interactions, including predator feeding deterrence and defense against fouling. Pyrrole-imidazole compounds, often involved in such ecological interactions, are exclusively found in marine sponges, mainly from the genera Axinella and Agelas. Employing field and laboratory assays, we studied the chemical defense of 2 co-occurring Mediterranean sponges, Axinella polypoides and A. verrucosa, collected from the Gulf of Naples, Italy, against microbial fouling, as well as their feeding deterrence against the generalist shrimp Palaemon elegans. These assays revealed no activity in the extracts of A. polypoides, while the n-butanol part of the A. verrucosa extract showed activity in all assays at natural concentrations. This fraction of the extract contains the bromopyrrole hymenidin, and our assays revealed antibacterial and feeding deterrence activity for this pure compound. 1H nuclear magnetic resonance quantification confirmed the presence of hymenidin and debromo-carteramine A, another previously isolated antibacterial compound, at ecologically relevant concentrations in the n-butanol part of the A. verrucosa extract. Our results indicate different antimicrobial and feeding deterrence defense strategies in the 2 examined sympatric sponge species, and multiple defensive roles of hymenidin in the defense of A. verrucosa, similar to those of other bromopyrroles isolated from taxonomically related Caribbean sponges.

Predation and competition are important factors structuring Antarctic benthic communities and are expected to promote the production of chemical defenses. Tunicates are subject to little predation, and this is often attributed to chemical compounds, although their defensive activity has been poorly demonstrated against sympatric predators. In fact, these animals, particularly the genus Aplidium, are rich sources of bioactive metabolites. In this study, we report the natural products, distribution and ecological activity of two Aplidium ascidian species from the Weddell Sea (Antarctica). In our investigation, organic extracts obtained from external and internal tissues of specimens of A. falklandicum demonstrated to contain deterrent agents that caused repellency against the Antarctic omnivorous predator, the sea star Odontaster validus. Chemical analysis performed with Antarctic colonial ascidians Aplidium meridianum and Aplidium falklandicum allowed the purification of a group of known bioactive indole alkaloids, meridianins A-G. These isolated compounds proved to be responsible for the deterrent activity. Funding was provided by the Ministry of Science and Education of Spain through the ECOQUIM Projects (REN2003-00545, REN2002-12006E ANT and CGL2004-03356/ANT).

Chemical investigation of the liposoluble extract of the gorgonian Acanthogorgia turgida, from Indian coasts, led us to isolate a new xenicane-based norditerpene, isoacalycixeniolide-A (1), along with the known structurally related compounds 2-6. The structure of the norditerpene (1) was elucidated by spectral methods (mainly by NMR techniques), whereas the absolute stereochemistry was suggested by the application of circular dicroism methodology.

Two new cembrane diterpenes, sinulaparvalides A and B (1 and 2, resp.), which contain an intriguing seven-membered lactone moiety, along with the four known related cembranoids 3-6, were isolated from the Hainan soft coral Sinularia parva. The structures of compounds I and 2 were established by spectroscopic methods, mainly on the basis of 2D-NMR techniques, and were confirmed by single-crystal X-ray diffraction analysis. The in vitro cytotoxic activities of these compounds were tested on human colon carcinoma (HCT-116), human promyelocytic leukemia (HL-60), and human lung carcinoma (A-549) tumor cell lines.

Chemical investigation of the lipophilic extract of the Antarctic soft coral Alcyonium grandis led us to the finding of nine unreported sesquiterpenoids, 2-10. These molecules are members of the illudalane class and in particular belong to the group of alcyopterosins, illudalanes isolated from marine organisms. The structures of 2-10 were determined by interpretation of spectroscopic data. Repellency experiments conducted using the omnivorous Antarctic sea star Odontaster validus revealed a strong activity in the lipophilic extract of A. grandis against predation.

The chemical investigation of the marine pulmonate Onchidium sp. and of its defensive mucous secretion led us to the isolation of a novel polypropionate, onchidione (4), containing two gamma-pyrone rings. The structure of 4 was elucidated by spectroscopic methods, mainly NMR techniques, and secured by X-ray analysis on a single crystal. (C) 2009 Elsevier Ltd. All rights reserved.

Chemical investigation of endemic Algerian plant Launaea arborescens resulted in the isolation of a series of triterpenes and sesquiterpenes from both the aerial parts and roots. Five terpenoids have been chemically characterised by means of spectral methods mainly NMR techniques. In addition, the absolute stereochemistry at the chiral carbon in the side chain of 8-deoxy-15-(3'-hydroxy-2'-methyl-propanoyl)-lactucin-3'-sulfate (6) has been determined by comparison of the (1)H NMR spectra of Mosher derivatives of 6 with those of the corresponding MTPA esters of model compounds.

Chemical investigation of the culture broth of the fungus Eutypella scoparia ICB-OBX, isolated from the marine pulmonate mollusc Onchidium sp., led to the finding of novel compounds 1 and 2 , structurally related to angiotensin II binding inhibitors cytosporins, along with unrelated known nitrogen metabolites (compounds 3 – 5 ). The structure and the relative stereochemistry of the novel metabolites were assigned mainly by a detailed analysis of two-dimensional NMR techniques whereas the absolute stereochemistry was proposed by modified Mosher's method. Compound 2 contains an unusual cyclic carbonate functionality that is rare among natural products.

With the aim of establishing whether the oxidation of the tricyclic carbon skeleton of scalaradial (1) is specific to Glossodoris mollusks, the chemical investigation of specimens of Glossodoris pallida from two distinct geographical areas (China and Guam) and of Glossodoris vespa and Glossodoris averni from Eastern Australia was performed. 12-Deacetoxy-12-oxo-scalaradial (4), recently reported from another Glossodoris nudibranch, was the main metabolite of G. pallida from China, G. vespa, and G. averni. A series of scalarane compounds 3 and 5-11, including the unprecedented 12,16-deacetoxy- 12-oxo-scalarafuran 5, was isolated from the mollusks. Interestingly, a population of G. pallida from Guam displayed a different scalarane pattern that was characterized by scalaradial (1), deacetyl scalaradial (2), and deoxoscalarin (3), thus confirming previous reports. The specific occurrence of 12-keto-derivatives in some nudibranchs of the genus Glossodoris is discussed.

Three unprecedented diastereoisomeric dimers, cis-dimer A (1), cis-dimer B (2) and trans-dimer C (3), exhibiting a bis-bisabolene skeleton, and a new sesquiterpene, dehydrotheonelline (4), their potential precursor, have been isolated from the South China Sea sponges Axinyssa variabilis and Lipastrotethya ana, along with known related sesquiterpenes. The structure of the novel molecules has been determined by extensive NMR spectral analysis.

The functionalization of the B-ring of the scalarane framework has been achieved for the first time by a radical relay halogenation (RRH) synthetic method. The known scalaranic methyl ester, which was prepared by a procedure with an overall yield higher than those reported in the literature, has been used as the starting substrate. Some theoretical considerations explaining the course of RRH reaction are also presented.

The glycoterpenoid syphonoside (1) is the main secondary metabolite of both the marine mollusk Syphonota geographica and the sea-grass Halophila stipulacea, two Indo-Pacific species migrated to the Mediterranean Sea through the Suez Canal. The structure and the absolute stereochemistry of 1, which displays unique structural features, has been accomplished by using a combination of spectroscopic techniques, degradation reactions, and conformational analysis methods. Compound 1 was able to inhibit high density induced apoptosis in a number of human and murine carcinoma cell lines.

Chemical analysis of the secondary metabolite pattern of the nudibranch Hexabranchus sanguineus collected from the South China Sea revealed the presence of both sesquiterpenoids and diterpenoids, exhibiting very different structural features. Two new molecules, compounds 1 and 4, were isolated together with known compounds 2 and 3, and chemically characterized. This is the first report of terpenoids from H. sanguineus. The remarkable diversity of metabolites possessed by H. sanguineus supports some recent phylogenetic studies that place the mollusc near the steam of the dorid nudibranch tree.

[EN] Puupchenone (1) and a series of its congeners (2-6) have been isolated from a Dysidea sponge. The unprecedented 20-acetoxyhater-unnadienone (2) exhibiting a five-membered contracted ring, has been characterized. In addition, stereochemical assignment of two previously reported acetone adducts of puupehenone (5 and 6) has been made. Finally, the inhibition of mitochondrial respiratory chain as well as antibacterial and antifungal activities of all compounds has been evaluated. (c) 2006 Elsevier Ltd. All rights reserved., This research has been partially funded by an Italian–Chinese bilateral project.

Allelopathy has been postulated as a factor in the colonisation success of Caulerpa racemosa var. cylindracea, an introduced chlorophyte alga which has become invasive in the Mediterranean Sea. In order to reveal their possible phytotoxic activity, secondary metabolites were isolated from a population growing in the Gulf of Naples (Italy) and tested on leaf tissue of the native seagrass Cymodocea nodosa, which often co-occurs with Caulerpa in nature. The seaweed metabolites were identified by H-1 and C-13 NMR analysis and leaf portions of C. nodosa were exposed to crude diethyl ether extract and purified compounds in the laboratory, under controlled conditions of irradiance and temperature for a period of 144 h. Eventual changes in the photosynthetic performance of the seagrass tissue following the treatment were tested by monitoring its optimal quantum yield with a pulse amplitude modulated (PAM) fluorometer. One of the identified compounds, caulerpenyne, showed a phytotoxic effect, while the other purified metabolites did not reveal any effect at the assayed concentrations. Thus, our results seem to suggest a possible allelopathic activity of caulerpenyne, which may play a role in the successful competition of the invasive C. racemosa var. cylindracea with native macrophytes, such as seagrasses.

Two new polyhydroxylated steroids, (2β,3β,4α,5α,8β,11β)-4-methylergost-24(28)-ene-2,3,8,11-tetrol-(1) and (3β,5α,6β)-ergosta-22,24(28)-diene-3,5,6,19-tetrol (3), together with the six known related steroids 2 and 4–8, were isolated from the Hainan soft coral Sinularia sp. Their structures were elucidated on the basis of spectroscopic analysis and by comparison with previously reported data. The structure of the known compound 9 (hyrtiosterol) was revised as 2 by extensive analysis of the ROESY data and by the NOE difference experiment.

Isomeric cheilanthane sesterterpenoids have been obtained stereospecifically by two different synthetic pathways. Superacidic, low-temperature cyclization of C 25 substrates (13E-bicyclogeranylfarnesoic acid methyl esters) led to 14α-cheilanthanes, along with other compounds, whereas the side-chain extension of a C 20 precursor (ent-isocopalic alcohol) afforded 14β-cheilanthanes. The synthesized compounds could be considered as useful synthons in the preparation of bioactive natural cheilanthanes and structurally related sesterterpenoids.

Three novel halogenated C15-acetogenins, compounds 1–3 , have been isolated, together with known metabolites, from a South China Sea collection of the anaspidean mollusc Aplysia dactylomela. The structures have been suggested by both NMR analysis and comparison with literature data. The structure of 1 was confirmed by a single crystal X-ray study, which also allowed the establishment of its absolute stereochemistry.

Two Ceratosoma species, C. trilobatum and C. gracillimum (Mollusca: Gastropoda: Opistobranchia), collected along the South China Sea coast, have been studied in order to investigate their defensive strategies. Both species contain four typical sponge furanosesquiterpenoids, probably with a dietary origin. The tissue distribution of these compounds has been studied by(1)H-NMR analysis and preliminary bioassays have been carried out in order to evaluate the ecological role of the isolated metabolites. The main sesquiterpene component in both species was (-)- furodysinin (2), which showed significant feeding-deterrent and ichthyotoxic properties in bioassays with freshwater organisms. The work has been performed studying a very limited number of molluscs that prevented the realization of ecologically relevant experiments. However, the almost exclusive presence of compound 2 in the crude extract of the mantle glands concentrated in the dorsal horn of C. gracillimum strongly supports the defensive role of that dorsal protuberance, which probably acts as a defensive lure attracting potential predators to the part of the animal that contains the distasteful chemicals.

A new gamma-pyrone propionate, compound 9, and its peroxy derivative 10 have been isolated from the sacoglossan Placobranchus ocellatus. The structure and the relative stereochemistry of the new molecules, which displayed an unprecedented carbon skeleton characterised by a bicyclo [4.2.0] octane, have been determined by both spectroscopic methods and comparison with model compounds. By analogy with photodeoxytridachione (2), a sunscreen protective role could be also suggested for compound 9 in living P. ocellatus.

Five new uncommon polyoxygenated steroids, namely suberoretisteroids A-E (1-5), were isolated from the gorgonian Suberogorgia reticulata, never studied so far. The structures and relative configurations of these new compounds were elucidated on the basis of extensive spectral analysis. This work led to the structural revision of some steroids previously found in the Indian gorgonian Gorgonella umbraculum.

Two new compounds, pregnanes 1 and 2 , the known pregnane 3 and a series of known chlorinated prostanoids ( 4 – 9 ) have been isolated from the Indian octocoral Carijoa sp. Their structures have been elucidated by spectroscopic methods, mainly by 1D and 2D NMR. The new compounds were potent inhibitors of the mitochondrial respiratory chain.

Four novel straight-chain polyacetylenic alcohols were isolated from a marine ascidian (Phylum Chordata, subphyllum Urochordata) collected off Vigo, along the Atlantic coast of northwestern Spain. The chemical structures, which exhibit an uncommon dienyne group, were characterized by spectroscopic methods, mainly mono- and bi-dimensional NMR. This is the first finding of acetylenic lipids from an organism belonging to phylum Chordata.

The use of stable isotopes has been recently introduced in the biosynthetic studies of metabolites produced by opisthobranch molluscs. This methodology offers numerous advantages since it avoids the complex and tedious manipulations of potentially dangerous radioactive compounds and gives unequivocal evidence for the incorporation. In these studies, high field NMR spectroscopy is a particularly useful tool to localize the labeled atoms in the molecule. This chapter updates the biosynthetic studies on opisthobranch molluscs with particular attention to the recent experiments with precursors labeled with stable isotopes. Opisthobranchs are able to biosynthesize de novo a wide array of chemical skeletons including polyketides, polypropionates, acetogenins, and terpenoids. The studies regarding this latter class is proposed in the light of the recent debate about classical and independent mevalonate pathway.

The diterpenoid acylglycerol fraction from an extract of the mantle of a new collection of the Antarctic dorid gastropod mollusc Austrodoris kerguelenensis has been chemically analysed. Two novel 2-monoacylglycerols 9 and 12 , along with known 1,2-diacyl glyceryl esters 5 and 6 , now reassigned as 7 and 8 , have been isolated. The linkage of a diterpenoid moiety at C-2 of glycerol characterizes all the compounds. Because the R absolute stereochemistry at C-2 of glycerol has been established for the corresponding 1,3-glyceryl esters 1 and 2 , derived from 7 and 8 by acyl-migration of the terpenoid moiety from C-2 to C-3, our finding implies that 1,2-derivatives from Antarctic nudibranchs have the same S stereochemistry as all 1,2-sn-diacylglycerols from the other dorids.

The common Antarctic nudibranch Austrodoris kerguelenensis (Bergh) contains diterpene diacylglycerides only present in its external body parts. These compounds provide a chemical defense against sympatric predators, such as the seastar Odontaster validus Koehler. Bioassays conducted with O. validus revealed that live nudibranchs, mantle tissue and Et2O extract of the A. kerguelenensis mantle deterred feeding by the seastar. Further bioassays testing organic fractions of the Et2O mantle extract showed that the diterpene diacylglycerides, as well as corresponding monoacylglycerides and monoacylglycerides of regular fatty acids, were responsible for the feeding deterrence in O. validus. We suggest that A. kerguelenensis derives the bioactive diacylglycerides by de novo biosynthesis rather than by sequestration from its sponge diet, since the mollusk does not contain active metabolites in the viscera, and neither the active compounds nor precursors were detected in the sponge diet. Furthermore, A. kerguelenensis did not show a strong chemodetection or feeding preference for its main diet, hexactinellid sponges, in Y-maze and food choice experiments, respectively.

The chemical investigation of the marine pulmonate Onchidium sp. and of its defensive mucous secretion led us to the isolation of a novel polypropionate, onchidione (4), containing two g-pyrone rings. The structure of 4 was elucidated by spectroscopic methods, mainly NMR techniques, and secured by X-ray analysis on a single crystal.

Northuridillonal (I), dihydronorthuridillonal (IIa) and deacetyldehydronorthuridillonal (IIb) are isolated and their structures are evaluated.

The Mediterranean dorid nudibranch Peltodoris atromaculata that had been collected while feeding on Haliclona fulva was shown to sequester long-chain fulvinol-like polyacetylene metabolites (compounds 2–5) from the prey. They were isolated along with previously reported bromorenierins from the diethyl ether extracts of both the mollusk and the sponge. Their structures were elucidated by NMR spectroscopy and tandem FABMS analysis. Compound 5 exhibited in vitro growth inhibitory effects against the SKMEL-28 melanoma cell line.

The re-investigation of the Mediterranean opisthobranch Thuridilla hopei resulted in the isolation and chemical characterization of three novel nor-diterpene aldehydes, nor-thuridillonals 2-4, structurally related to co-occurring already reported thuridillins. Analogous with the thuridillins, the new molecules were thought to derive from the same dietary precursor epoxylactone 1. © 2014 Elsevier Ltd. All rights reserved.

The first study on the biosynthesis of terpenoid metabolites in the porostome nudibranch Doriopsilla areolata is described herein. The de novo origin of two different groups of bi- and tri-cyclic sesquiterpenes, exhibiting opposite A/B ring junctions, has been clearly demonstrated by in vivo incorporation of labeled mevalonate. Surprisingly, metabolites of both series have been previously reported to co-occur in a sponge of genus Dysidea , that could be included in the diet of the nudibranch.

Three porostome nudibranchs, Dendrodoris krebsii from Mexico, Doriopsilla albopunctata from California and Doriopsilla areolata from Portugal, have been chemically investigated. The presence of sesquiterpenes of the drimane class in these molluscs has been confirmed. In addition, these species have shown to contain sesquiterpenes of ent-pallescensin-A (or pallescensin-A) series, co-occurring with drimane metabolites. Most of these sesquiterpenes are typical sponge metabolites, suggesting a dietary origin in the molluscs, even though de novo biosynthesis, rigorously demonstrated for some Dendrodoris molluscs, may occur.

Eight sacoglossan species associated with green algae and collected along Caribbean coasts have been chemically investigated, together with their prey. The main secondary metabolites have been identified either by TLC comparison with standard compounds, or by 1H NMR analysis, defining dietary relationships. In addition, two new compounds, ascobullin-A and ascobullin-B, have been found in the sacoglossan Ascobulla ulla and characterized by spectroscopic methods. Finally, the results obtained, together with those already reported for Caribbean sacoglossans, are summarized in a chemoecological scenario, which could be compared with that previously proposed for Mediterranean species.

The superacidic cyclization of all-trans-w-acetoxyfarnesyl benzyl ether 2 begins at the internal double bond giving a mixture of diastereomeric monocyclic compounds 5 and 6, prenylated at gem-dimethyl groups.

Two novel diterpenoid 2'-monoglyceryl esters, austrodorin-A (7) and austrodorin-B (8), which contain the isocopalane skeleton with an uncommon oxygenated substitution pattern, have been isolated from the skin of the Antarctic nudibranch Austrodoris kerguelenensis. Structures and relative stereochemistries have been established by NMR methods, whereas the absolute configuration was suggested by comparison of their CD profiles with those of model compounds. (C) 1999 Elsevier Science Ltd. All rights reserved.

Four new N-acyl-2-methylene-β-alanine methyl esters, named hurghamides A-D (6–9), together with two known analogues 2a and 2b, were isolated from a Red Sea sponge Hippospongia sp. Their structures were elucidated by extensive spectroscopic studies.

Sacoglossan sea slugs are a group of opisthobranch herbivorous mollusks primarily associated to siphonalean green algae. They appear to be one of the few metazoan groups to retain functional chloroplasts as intracellular organelles. Species belonging to Elysia genus are characterized for large parapodia, which contain the digestive diverticulum where the chloroplasts sequestered are photosynthetically functional for many days to months, useful for the survival of the mollusks. Elysia patagonica Muniain and Ortea (1997) (Plakobranchidae, Sacoglossa) is the first sacoglossan described from Argentina, and intact chloroplasts of the green algae Bryopsis cf. plumosa (Chlorophyta: Bryopsidales) were observed in the digestive cells of benthic adults starved for many days Fil: Carbone, Marianna. Consiglio Nazionale delle Ricerche; Italia Fil: Muniain, Claudia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín; Argentina Fil: Castelluccio, Francesco. Consiglio Nazionale delle Ricerche; Italia Fil: Iannicelli, Olga. Consiglio Nazionale delle Ricerche; Italia Fil: Gavagnin Capoggiani, Margherita. Consiglio Nazionale delle Ricerche; Italia

BackgroundStorage of secondary metabolites with a putative defensive role occurs in the so-called mantle dermal formations (MDFs) that are located in the more exposed parts of the body of most and very likely all members of an entire family of marine mollusks, the chromodorid nudibranchs (Gastropoda: Opisthobranchia). Given that these structures usually lack a duct system, the mechanism for exudation of their contents remains unclear, as does their adaptive significance. One possible explanation could be that they are adapted so as to be preferentially attacked by predators. The nudibranchs might offer packages containing highly repugnant chemicals along with parts of their bodies to the predators, as a defensive variant of the strategic theme of the Trojan horse.Methodology and principal findingsWe detected, by quantitative (1)H-NMR, extremely high local concentrations of secondary metabolites in the MDFs of six species belonging to five chromodorid genera. The compounds were purified by chromatographic methods and subsequently evaluated for their feeding deterrent properties, obtaining dose-response curves. We found that only distasteful compounds are accumulated in the reservoirs at concentrations that far exceed the values corresponding to maximum deterrent activity in the feeding assays. Other basic evidence, both field and experimental, has been acquired to elucidate the kind of damage that the predators can produce on both the nudibranchs' mantles and the MDFs.SignificanceAs a result of a long evolutionary process that has progressively led to the accumulation of defensive chemical weapons in localized anatomical structures, the extant chromodorid nudibranchs remain in place when molested, retracting respiratory and chemosensory organs, but offering readily accessible parts of their body to predators. When these parts are masticated or wounded by predators, breakage of the MDFs results in the release of distasteful compounds at extremely high concentration in a way that maximizes their repugnant impact.

Here, we present a minimal hybrid ligand/receptor-based pharmacophore model (PM) for CXCR4, a chemokine receptor deeply involved in several pathologies, such as HIV infection, rheumatoid arthritis, cancer development/progression, and metastasization. This model, considerably simpler than those thus far proposed for this receptor, has been used to search for new CXCR4 inhibitors in a small marine natural product library available at ICB-CNR Institute (Pozzuoli, NA, Italy), since natural products, with their naturally selected chemical and functional diversity, represent a rich source of bioactive scaffolds; computational approaches allow searching for new scaffolds with a minimal waste of possibly precious natural product samples; and our "stripped-down" model substantially increases the probabilities of identifying potential hits even in small-sized libraries. This search, also validated by a systematic virtual screening of the same library, has led to the identification of a new CXCR4 ligand, phidianidine A (PHIA). Docking studies supported PHIA activity and suggested its possible binding modes to CXCR4. Using the CXCR4-expressing/CXCR7-negative GH4C1 cell line we show that PHIA inhibits CXCL12-induced DNA synthesis, cell migration, and ERK1/2 activation. The specificity of these effects was confirmed by the lack of PHIA activity in GH4C1 cells, in which siRNA highly reduces CXCR4 expression and the lack of cytoxicity of PHIA was also verified. Thus, PHIA represents a promising lead for a new family of CXCR4 modulators with wide margins of improvement in potency and specificity offered by the small and very simple underlying PM.

The isolation and structure elucidation of 10 unreported polypropionate metabolites (compounds 6-15), structurally related to either ilikonapyrone (1) or onchidione (3), from two onchidiid pulmonate mollusk species are discussed. Structure elucidation was achieved by NMR spectroscopy and chemical correlation with model compounds. Evaluation of in vitro growth-inhibitory properties in human cancer cells was also carried out on some of the isolated polypropionates including previously reported onchidione metabolites.

A new polypropionate, tridachiahydropyrone ( 3 ), displaying an unprecedented bicyclic γ-dihydropyrone carbon skeleton, has been isolated from the Caribbean sacoglossan molluse Tridachia crispata . The structure and the relative stereochemistry have been determined by spectroscopic methods.

A concise synthesis or two diastereoisomeric diterpenoid acid glycerides, la, previously isolated from the skin or some dorid nudibranchs, and 3, via 13E-labd-8(9),13-dienic acid 4, is described. Copyright (C) 1996 Elsevier Science Ltd

Petroformynes are unusual metabolites contained in the Mediterranean sponge Petrosia ficiformis. The structure and absolute stereochemistry of the most abundant of these compounds, which display long unbranched alkyl chains, have only recently been rigorously proven. The structures of twelve minor compounds are now reported, providing a better understanding of the chemistry of P. ficiformis. In addition, complete spectroscopic characterization of eleven partial structures (a-k) frequently contained in P. ficiformis metabolites is provided as an aid to future structure elucidation among compounds of this type.

This first chemical study of the sacoglossan mollusk Thuridilla splendens from Mooloolaba, South East Queensland, has resulted in the isolation of three new metabolites, thuridillins D-F (1-3), and one known metabolite, thuridillin A (4). Thuridillin D (1) was isolated by conventional flash chromatography on silica gel, while a mixture of thuridillins E (2) and F (3) was obtained by PTLC on AgNO(3)-impregnated silica gel. Thuridillins D-F were determined to be structurally related to thuridillin B (5); 1 possessed a hydroxy group at C-11, and 2 and 3 were Δ(10,11)- and Δ(11,12)-isomers, respectively. HSQC-HECADE NMR data, together with conformational analysis, NOESY experiments, and (1)H-(1)H coupling studies enabled assignment of the individual relative configurations of the epoxylactone, the 2,5-diacetoxy-2,5-dihydrofuran, and cyclohexyl moieties within thuridillin D (1).

Ascidians have developed multiple defensive strategies mostly related to physical, nutritional or chemical properties of the tunic. One of such is chemical defense based on secondary metabolites. We analyzed a series of colonial Antarctic ascidians from deep-water collections belonging to the genera Aplidium and Synoicum to evaluate the incidence of organic deterrents and their variability. The ether fractions from 15 samples including specimens of the species A. falklandicum, A. fuegiense, A. meridianum, A. millari and S. adareanum were subjected to feeding assays towards two relevant sympatric predators: the starfish Odontaster validus, and the amphipod Cheirimedon femoratus. All samples revealed repellency. Nonetheless, some colonies concentrated defensive chemicals in internal body-regions rather than in the tunic. Four ascidian-derived meroterpenoids, rossinones B and the three derivatives 2,3-epoxy-rossinone B, 3-epi-rossinone B, 5,6-epoxy-rossinone B, and the indole alkaloids meridianins A–G, along with other minoritary meridianin compounds were isolated from several samples. Some purified metabolites were tested in feeding assays exhibiting potent unpalatabilities, thus revealing their role in predation avoidance. Ascidian extracts and purified compound-fractions were further assessed in antibacterial tests against a marine Antarctic bacterium. Only the meridianins showed inhibition activity, demonstrating a multifunctional defensive role. According to their occurrence in nature and within our colonial specimens, the possible origin of both types of metabolites is discussed.

Hexactinellids (glass sponges) are an understudied class with syncytial organization and poor procariotic associations, thought to lack defensive secondary metabolites. Poriferans, though, are outstanding sources of bioactive compounds; nonetheless, a growing suspicion suggests that many of these chemicals could be symbiont-derived. In Polar latitudes, sponges are readily invaded by diatoms, which could provide natural products. Hexactinellids are typical of deep waters; but in Antarctica, they dominate the upper shelf providing shelter and food supply to many opportunistic mesograzers and macroinvertebrates, which exert strong ecological pressures on them. Aiming to examine the incidence of defensive activities of hexactinellids against consumption, feeding experiments were conducted using their lipophilic fractions. Antarctic hexactinellid and demosponge extracts were tested against the asteroid Odontaster validus and the amphipod Cheirimedon femoratus as putative sympatric, omnivorous consumers. Hexactinellids yielded greater unpalatable activities towards the amphipod, while no apparent allocation of lipophilic defenses was noted. After chemical analyses on the lipophilic fractions from these Antarctic glass sponges, quite similar profiles were revealed, and no peculiar secondary metabolites, comparable to those characterizing other poriferans, were found. Instead, the lipidic compounds 5α(H)-cholestan-3-one and two glycoceramides were isolated for their particular outspread presence in our samples. The isolated compounds were further assessed in asteroid feeding assays, and their occurrence was evaluated for chemotaxonomical purposes in all the Antarctic samples as well as in glass sponges from other latitudes by NMR and MS. Characteristic sphingolipids are proposed as chemical markers in Hexactinellida, with possible contributions to the classification of this unsettled class.

In this communication, selected results obtained in the course of a 10-year Sino-Italian collaborative project are presented. During this collaboration, several studies on marine organisms collected in the South China Sea have been conducted, resulting in the characterization of a large number of novel natural products. The main interest has been focused on sponges, cnidarians, and molluscs. Here, the recent research, including some not yet published studies, on cnidarians and molluscs, in particular, opisthobranchs and pulmonates, will be briefly described. The study of cnidarians and pulmonates led to isolate molecules, in particular, biscembranoids and polypropionates, displaying carbon skeletons already described in previous papers. Our studies resulted in their complete structural characterization including the absolute stereochemistry that was clarified by coupling X-ray diffraction to circular dichroism (CD) spectra analysis. Some unique nitrogenous molecules containing either an isonitrile function or an 1,2,4-oxadiazole moiety, this latter found for the first time in a marine organism, as well as known sesterterpenoids and diterpenoids were isolated from opisthobranchs. Owing to their anatomical location, these metabolites should play a relevant role in the protection of the molluscs. Finally, a series of alkaloids structurally related to known anticancer agents were also characterized.