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

✍ Scribed by Michele D'Ambrosio; Antonio Guerriero; Francesco Pietra; Cécile Debitus

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: German
• Weight: 647 KB
• Volume: 79
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19960790107

✦ Synopsis

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 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 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.