Stereoselective synthesis of the C 1–C 12 segment of iriomoteolide- 1a: a very potent macrolide antitumor agent

Abstract

A stereoselective synthesis of the C 1–C 12 segment of the potent cytotoxic macrolide, iriomoteolide 1a, has been accomplished. The key steps involve an enzymatic kinetic resolution of a β-hydroxy amide, a Pd-catalyzed cross-coupling to construct a substituted allylsilane, a highly and stereoselective conjugate addition of lithium dimethylcopper to an α,β-acetylenic ester and an elaboration of the C 6–C 7 trans-olefin geometry by a Julia-Kocienski olefination.