Synthesis of DNA-Encoded Macrocyclic Peptides via Visible-Light-Mediated Desulfurative C–C Bond Formation

DNA-encoded library (DEL) technology has been developed to serve as a practical platform for the discovery of biologically active macrocyclic peptide compounds. However, the cyclization of linear peptides has been widely regarded as the challenging step in the production of macrocyclic peptide DELs. Herein, we describe a novel DNA-compatible macrocyclization strategy, which enables the construction of ring systems via visible-light-mediated desulfurative C-C bond formation. The macrocyclization proceeds smoothly under mild conditions and in a good yield. Moreover, the reaction is compatible with a variety of linear substrates and can thus be employed to generate structurally diverse DNA-encoded macrocycles with various ring sizes.