Synthesis of Peptide Macrocycle via Metal-Catalyzed C-H Macrocyclization

Transition-metal-catalyzed C-H activation has emerged as a powerful macrocyclization tool with relevant applications in peptide drug discovery. This approach which exploits unactivated C-H bonds as nontraditional “handle” for C-C bond cyclization, has facilitated the chemical creation of new macrocyclic peptide topologies. In this article, we highlight the different established strategies for C(sp [[sup]]2[[/sup]] )-H and C(sp [[sup]]3[[/sup]] )-H functionalization to access macrocyclic peptides in which chemo- and regioselectivies were discussed. We consider that many exciting applications will emerge by applying the C-H activation approach to synthesize new macrocyclic topologies or rationally designed bioactive macrocyclic peptides.