Cu-catalyzed alkynylation of thiosulfonate-based peptide: an efficient approach to S-alkynyl-containing cyclic peptides†

Abstract

Cyclic peptides are highly valued in drug discovery due to their enhanced biological properties. Despite their potential, the construction of an S-alkynyl moiety in a cyclic peptide remains challenging due to limited synthetic strategies. Herein, we describe a copper-catalyzed alkynylation of thiosulfonate-based peptides, enabling efficient and selective synthesis of S-alkynylated cysteines and peptides. The adjustment of the amount of base could significantly increase the efficiency. This method features a broad substrate scope, operational simplicity and compatibility with complex peptide structures.