Stereoselective synthesis of the C1–C12 segment of iriomoteolide-1a: a very potent macrolide antitumor agent

A stereoselective synthesis of the C1–C12 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 C6–C7 trans-olefin geometry by a Julia-Kocienski olefination.