Synthesis of tyrocidine A and its analogues by spontaneous cyclization in aqueous solution

Abstract

[reaction: see text] Head-to-tail cyclization of peptides is a multistep process involving tedious C-terminal activation and side chain protection. Here we report a facile, quantitative cyclization method in aqueous ammonia solution for the total syntheses of the cyclic decapeptide antibiotic Tyrocidine A and its analogues from their fully deprotected linear thioester precursors on a solid support. This novel aqueous method is conformation-dependent and may be applicable to syntheses of other natural cyclic peptides.