Visible-light mediated selective phosphonylation modification of tryptophan residues in oligopeptides

Abstract

Despite their significant importance in biological and medicinal chemistry fields, the difficulties in the site-selective and diverse modification of biomolecules pose substantial obstacles to their applications. Here, we developed a direct C2–H phosphonylation strategy driven by visible light for specific modification of tryptophan containing peptides under exceedingly mild conditions, providing a straightforward and environmentally friendly synthetic method for the preparation of a plethora of phosphorylated tryptophan-containing peptides. Importantly, the protocol is applicable to the late-stage installation of phosphonate motifs into natural peptides, segetalin A and B, and their phosphonylation peptides exhibited better antiproliferative activity against HCT116 and HepG-2 compared with the original segetalins by a CCK-8 assay.