Leucascandrolide A, a New Type of Macrolide: The first powerfully bioactive metabolite of calcareous sponges (<i>Leucascandra caveolata</i>, a new genus from the coral sea)

Abstract

Abstract Leucascandrolide A ((+)‐ 1 ), a doubly O‐bridged 18‐membered macrolide of a new type, i.e. , showing little C 1 ‐branching vs. extensive 1,3‐dioxygenation and a peculiar side chain, was isolated from a calcareous sponge of a new genus, Leucascandra caveolata B OROJEVIC and K LAUTAU 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 Δδ = (δ( S ) − δ( 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 Δδ 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.