Chemoselective Peptide Backbone Diversification and Bioorthogonal Ligation by Ruthenium-Catalyzed C?H Activation/Annulation

Article abstract of DOI:10.1002/adsc.202100323

The field of peptide derivatization by metal-catalyzed C?H activation has been mostly directed to modify the side chains, but poor attention has been given to the peptide backbone. Here we report a ruthenium-catalyzed C?H activation/annulation process that can chemoselectively modify the peptide backbone producing functionalized isoquinolone scaffolds with high regioselectivity in a rapid and step-economical manner. This strategy is characterized by racemization-free conditions and the production of fluorescent peptides, and peptide conjugates to drugs, natural products and other peptide fragments, providing a chemical approach for the construction of novel peptide-pharmacophore conjugates. Mechanistic studies suggest that amide bonds of peptide backbone act as the bidentate directing group to promote the C?H activation/annulation process. This report provides an unprecedented example of peptide backbone diversification and bioorthogonal ligation exploiting the power of ruthenium-catalyzed C?H activation. (Figure presented.).