Leucascdndrolide A ((+)-l), a doubly 0-bridged 18-membered macrolide of a new type, i.e., showing little C,-branching vs. extensive 1,3-dioxygenation and a peculiar side chain, was isolated from a calcareous sponge of a new genus, Leucuscundra caveoluta BOROJEVIC and KLAUTAU from the Coral Sea. Transesterification of (+)-1 gave the methyl ester 3, derived from the side chain, and the 5-hydroxy derivative (+)-2, derived from the macrolide portion and with the natural configuration at C(5) (axial). Mosher's MTPA esters 4 and 5 obtained from (+)-2 showed scattered AS = (S(S) -6 ( R ) ) data. However, inversion of the configuration at C(5) led, via ketone (+)-6, to the less encumbered 5-equatorial hydroxy derivative (+)-7, whose MTPA esters 8 and 9 gave consistent AS data, allowing the assignment of the absolute configuration of (+)-7, and hence of (+)-1. The structural novelty of (+)-1 and its powerful antifungal and cytotoxic activities are likely to renew interest in calcareous sponges, previously limited to scarcely biologically active 2-aminoimidazoles.

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Agelastatin A, isolated from the axinellid sponge Agelas dendromorpha of the Coral Sea, is a new-skeleton alkaloid with, unusually for the oroidin family to which it belongs, marked cytotoxicity toward tumour cells in culture.

From the scleractinian coral Tubastraea sp. (Dendrophylliidae) collected at Palawan, Philippines, 3'-deimino-3'-oxoaplysinopsin (4) and 6-bromo-3'-deimino-3'-oxoaplysinopsin (6) are now isolated as 5 : 2 mixtures of ( E / Z ) stereoisomers. The 3'-deimino-2',4-bis(demethyl)-3'-oxoaplysinopsin (7) and 6-bromo-3'-deimino-2',4'-bis(demethyl)-3'-oxoaplysinopsin (5) are isolated as 2 :3 and 1 :1 (E/Z) mixtures, respectively, from another dendrophylliid, Leplopsammia pruuofi, collected near Marseille, Mediterranean coast of France. Larger amounts of these and related compounds, needed for a full structural determination, are obtained by synthesis. Thus, condensations of indol-3-carboxaldehyde (9) or of its 6-bromo derivative 14 with hydantoin (15), 3-methylhydantoin (ll), or 1,3-dimethylhydantoin (10) give the prevalent natural aplysinopsins with high stereospecificity. The minor stereoisomers (2)-4, (2)-6, (E)-7, and (E)-5 are obtained by (E/2) photoisomerization under UV light of the condensation mixtures. The configuration is assigned from larger H-C(S)/C(Y) ' H , ' k couplings in the ( E ) than in the ( Z ) isomer, and, in the case of 4 and 6, from NOE enhancement at Me-N(2') on irradiation at H-C(8). The stereospecificity of the condensations is attributed to steric inhibition to planarity in the rate-limiting transition states, due to N(2')/H-C(2) repulsion with (2)-4 and (2)-6, or to C(5')=0/H-C(2) repulsion with (E)-7 or (E)-5. As the aplysinopsins undergo (E/Z) photoisomerizdtion also under the daylight conditions of the kIbOrdtOry, their isomeric composition in nature can not be presently assessed.

Challenging questions are raised about the biosynthetic origin of vannusal A (1), a metabolite that is isolated from the tropical marine ciliate Euplotes vannus and contains an unusual C30 backbone.

(1 6.111.95)As compounds from a calcareous sponge, Leucetta sp., of the Coral Sea, we isolated a series of novel naamidine-type alkaloids, 6-10, which are oxidized at a single benzylic position. We also report on the first marine, mixed-ligand metal complex 5 and on the first natural metal complexes 3 and 4 derived from classical naamidines, i.e.. 1 and 2. The latter are also present in free form in the sponge.

Reported here is the first polyarsenic compound ever found in nature. Denominated arsenicin A, it was isolated along a bioassay-guided fractionation of the organic extract of the poecilosclerid sponge Echinochalina bargibanti collected from the north-eastern coast of New Caledonia. In defining an adamantine-type polyarsenic structure for this compound, deceptively simple NMR spectra were complemented by extensive mass spectral analysis. However, it was only the synthesis of a model compound that provided the basis to discriminate structure 4 from other spectrally compatible structures for arsenicin A; to this end, a comparative ab initio simulation of IR spectra for the natural and the synthetic compounds was decisive. Arsenicin A is endowed with potent bactericidal and fungicidal activities on human pathogenic strains. All this may revive pharmacological interest in arsenic compounds while prompting us to rethink the arsenic cycle in nature.

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