Metal-Catalyzed C(sp2)-H Functionalization Processes of Phenylalanine- and Tyrosine-Containing Peptides

The site-selective chemical diversification of biomolecules constitutes an unmet challenge of capital importance within medicinal chemistry and chemical biology. The functionalization of otherwise unreactive C-H bonds holds great promise for reducing the reliance on existing functional groups, thereby streamlining chemical syntheses. Over the last years, a myriad of peptide labelling techniques featuring metal-catalyzed C-H functionalization reactions have been developed. Despite the wealth of reports in the field, the site-selective modification of both phenylalanine (Phe) and tyrosine (Tyr) compounds upon metal catalysis remain comparatively overlooked. This review highlights these promising tagging strategies, which generally occur through the formation of challenging 6-membered metallacycles and enable the late-stage diversification of peptides in a tailored fashion.

Automated summary

The challenge of site-selective chemical diversification of biomolecules is important in medicinal chemistry and chemical biology. Functionalizing unreactive C-H bonds has the potential to simplify chemical syntheses. Metal-catalyzed peptide labelling techniques and site-selective modification challenges are discussed, with promising strategies highlighted for late-stage diversification of peptides through 6-membered metallacycles formation.