Total Syntheses of Cathepsin D Inhibitory Izenamides A, B, and C and Structural Confirmation of Izenamide B

Abstract

The first total syntheses of izenamides A, B, and C, which are depsipeptides inhibitor of cathepsin D, were accomplished. In addition, the stereochemistry of izenamide B was confirmed by our syntheses. The key features of our synthetic route involve the avoidance of critical 2,5-diketopiperazine (DKP) formation and the minimization of epimerization during the coupling of amino acids for the target peptides.

Keywords

• izenamides
• cathepsin D
• depsipeptide
• total synthesis
• structural confirmation