Total Synthesis of Epothilone E and Analogues with Modified Side Chains through the Stille Coupling Reaction

Abstract

Ring-closing metathesis (step a in the scheme below), deprotection (b), Stille coupling (c), and epoxidation (d) are the key steps in the first total synthesis of the naturally occurring epothilone E (1). An advanced intermediate, the product of the olefin metathesis, allows access to a range of epothilone E analogues having different aromatic moieties in the side chain. TBS = tBuMe2Si.