Silica-Phase Synthesis of Kahalalide B and Its Analogues

Abstract

Kahalalide B 4a and its analogues 4b-e were synthesized via solid-phase peptide synthesis on silica and imidazole-catalyzed macrolactonization. Thus, the peptide immobilization onto the functionalized mercaptophenyl silica gel 1 followed by removal of the resin support and the O-protecting group gave the peptide thioester 3. Imidazole (1.5 M) catalyzed the macrolactonization of 3 to afford the corresponding cyclic depsipeptides 4 in 80-98% yield.