Total synthesis and stereochemistry establishment of tumescenamide A

Abstract

Tumescenamide A (1), isolated from Streptomyces tumescens YM23-20, consists of a cyclic depsipeptide and a side-chain 2,4-dimethylheptanoate (Dmh). Herein, we report the first total synthesis of tumescenamide A (1) and establish its stereochemistry. The configuration of Dmh is 2S,4S and, notably, the configuration of Val is revised as D. In addition, a mild and practical method for the β-elimination of derivatives of serine and threonine by using nano-K₂CO₃ as a base was established. A highly stereoselective synthesis of the Dmh substructure was also developed.