Synthesis of (−)-Cephalosporolide D Using an Iterative Acetylene–Epoxide Coupling Strategy

Abstract

Abstract The synthesis of an eight-membered lactone, cephalosporolide D is described using an iterative acetylene–epoxide coupling strategy. The terminal triple bond compound prepared in situ from the known epoxy chloride was coupled with (R)-methyloxirane to afford the propargyl alcohol. The selective protection of the propargylic hydroxy group as TBS ether followed by reduction of the triple bond gave the saturated alcohol. Removal of THP group followed by selective oxidation of the primary hydroxy group was achieved using BAIB–TEMPO to furnish the aldehyde, which was converted to the corresponding acid by Pinnick oxidation, followed by Yamaguchi lactonization and finally removal of the TBS group afforded the target molecule. A concise synthesis of (−)-cephalosporolide D is described. The salient features are the utilization of acetylene–epoxide coupling strategy and Yamaguchi lactonization.