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.

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.

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Agelastatin A (1), an unusual alkaloid of the axinellid sponge Agelas dendromorpha from the Coral Sea, can be selectively acetylated (→7) or methylated at OHC(8a) (→4), peracetylated (→8) or permethylated at OHC(8a), NH(5), and NH(6) (→5), or, finally, subjected to C(9)C(8a) (→14) or C(5b)C(8a) β‐elimination (→11–13), in a regiospecific manner or not, depending on the reaction conditions. Under acidic conditions, compound 12 adds H2O or MeOH, regioselectively though not endo/exo stereoselectively, giving transoid/cisoid mixtures 1/18 or 4/19, respectively. Similarly 11 or 13 add MeOH to give mixtures (−)‐2/20 or 15/16, respectively. Compound 13 also adds AcOH giving mixture 8/17. The intermediate cisoid form obtained on treatment of 21 with H3O+ undergoes N(5)N(6) bridging affording pentacyclic 22 which constitutes a proof for the cisoid configuration. From conformational studies, rules are devised that allow assigning the configuration of these compounds from NMR data. In vitro comparative cytotoxicity assays of these compounds show that for high cytotoxic activity, such as of 1 in vivo, unsubstituted OHC(8a), HN(5), HN(6) moieties are needed in the natural B/D transoid configuration.

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