Synthesis of\nDNA-Encoded Macrocyclic Peptides via\nVisible-Light-Mediated Desulfurative C–C Bond Formation

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