First Stereoselective Total Synthesis and Biological Evaluation of Amphidinin B and Its Analogues

A highly stereoselective first total synthesis of amphidinin B is described. The key steps involved in this synthesis are the generation of the exo-double bond in the C-1-C-9 segment, the Barbier allylation, enzymatic kinetic resolution, and the construction of the C-10-C-21 segment by Sharpless asymmetric epoxidation, base-induced epoxide ring-opening, radical cyclization, diastereoselective reduction of the exo-cyclic double bond, one-pot allylation followed by debenzylation, Evans alkylation, and Yamaguchi esterification.