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 there potential, the construction of S-alkynyl moiety in a cyclic peptides 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.