Selective Photoredox Trifluoromethylation of Tryptophan-Containing Peptides

For application in drug discovery and biomedicine, it is crucial to develop new biocompatible methods to modify polypeptides. Herein, a visible-light-induced photoredox trifluoromethylation of tryptophan-containing peptides is reported. Under a mild, biocompatible, and straightforward condition, this strategy could incorporate the trifluoromethyl group into tryptophan residue with excellent chemo- and site-selectivity. The use of lower photocatalyst loading in 2 mol-% and cheap CF3SO2Na salt represents a great catalytic activity and economic CF3 source. This direct trifluoromethylation strategy allows the ready study of fluorinated peptides exploiting F-19-NMR. Additionally, the development of this protocol enables the study of biochemical systems and potentially modulates the function of biomolecules. Careful mechanistic studies (Stern-Volmer fluorescence quenching, EPR, and radical inhibition/trapping experiments) indicate that the reaction would proceed with a radical-radical cross-coupling procedure.