Postassembly Modifications of Peptides via Metal-Catalyzed C-H Functionalization

The growing importance of peptides and proteins in therapeutic and biomedical applications has provided immense motivation toward the development of new ways to construct and transform peptide molecules. As in other areas of organic synthesis, C-H functionalization (CHF) chemistry could potentially exemplify disruptive technologies for peptide engineering. Over the past decade, the field has witnessed an exciting surge of reports of various metal-catalyzed CHF chemistry for postassembly modification of peptides and proteins. This review chronicles present advances in this research area up to June 2020. The content is organized based on the location of CHF on peptides: amino acid side chains (aromatic and nonaromatic), backbone, and appendant groups on peptide terminus. In addition to the reaction mechanisms of the metal-catalyzed CHF chemistry used in these peptide modification protocols, brief comments on the corresponding nonmetal-mediated strategies are included to provide readers a broad view of the current status of CHF-enabled peptide modification.