Total Syntheses of Disorazoles A₁and B₁and Full Structural Elucidation of Disorazole B₁

Abstract

Described herein are the first total syntheses of naturally occurring antitumor agents disorazoles A₁ and B₁ and the full structural assignment of the latter. The syntheses were achieved through convergent strategies employing enantioselective constructions of the required building blocks, including a novel Sharpless epoxidation/enzymatic kinetic resolution of stannane-containing substrates that led selectively to both enantiomeric forms of an epoxy vinyl stannane, and a series of coupling reactions, including a Wittig reaction, a Suzuki coupling, a Stille coupling, a Yamaguchi esterification and a Yamaguchi macrolactonization.