Total synthesis of 12,13-desoxyepothilone B (Epothilone D)

A highly convergent total synthesis of 12,13-desoxyepothilone B (4, Epothilone D) is described involving the coupling of vinyl. iodide (5) and olefin (6). Key steps in the synthesis are the introduction of chirality at C15 via highly enantioselective lipase-mediated enzymatic resolution, diastereoselective alkylation at C8, highly diastereoselective Evans aldol reaction to establish C6-C7, and Mukaiyama aldol reaction to introduce chiral center C3. Palladium catalyzed Suzuki coupling of (5) and (6) provided the methyl ester (27), which was converted to 12,13-desoxyepothilone B (4). (c) 2004 Elsevier Inc. All rights reserved.