Total synthesis of Filipin III.

Filipin III (1), a polyene macrolide antibiotic, has been synthesized for t he first time. The polyol chain was assembled using a stereoselective carbo n-carbon bond forming strategy previously developed in our lab: a cyanohydr in acetonide alkylation and reductive decyanation sequence. The polyene seg ment was prepared from L-ascorbic acid. These two components were coupled u sing Yamaguchi's esterification, and cyclized with an intramolecular Homer- Emmons reaction to form a trisubstituted alkene. Stereoselective reduction followed by deprotection gave filipin III. This highly convergent approach to filipin III represents the first total synthesis of a methylpentaene mac rolide antibiotic. (C) 1999 Elsevier Science Ltd. ALI rights reserved.