LEUCASCANDROLIDE-A, A NEW-TYPE OF MACROLIDE - THE FIRST POWERFULLY BIOACTIVE METABOLITE OF CALCAREOUS SPONGES (LEUCASCANDRA-CAVEOLATA, A NEW GENUS FROM THE CORAL SEA)

Leucascandrolide A ((+)-1), a doubly O-bridged 18-membered macrolide o f a new type, i.e., showing little CI-branching vs. extensive 1,3-diox ygenation and a peculiar side chain, was isolated from a calcareous sp onge of a new genus, Leucascandra caveolata 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, deriv ed from the macrolide portion and with the natural configuration at C( 5) (axial). Mosher's MTPA esters 4 and 5 obtained from (+)-2 showed sc attered Delta delta = (delta(S) - delta(R)) data. However, inversion o f the configuration al C(5) led, via ketone (+)-6, to the less encumbe red 5-equatorial hydroxy derivative (+)-7, whose MTPA esters 8 and 9 g ave consistent Delta delta data, allowing the assignment of the absolu te 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 scarcel y biologically active 2-aminoimidazoles.