Dimethyl Sulfoxide/Visible-Light Comediated Chemoselective C-S Bond Formation Between Tryptophans and Thiophenols Enables Site-Selective Functionalization of Peptides

Late-stage peptide modification showcases a huge potential for the construction of peptide libraries, and the investigation of structure-activity relation-ships. Herein we report a dimethyl sulfoxide/visible light comediated chemoselective modification of tryptophan residue by forging the C-S structure using thiophenols irradiated with blue light-emitting diodes at room temperature. This method shows excellent chemoselectivity toward the C-2 position of the tryptophan residue and good compatibility with diverse thiophenol derivatives bearing various functional groups. Both protected oligopeptides and unmasked bioactive peptides smoothly underwent site-selective modification, furnishing the corresponding products. Above all, this study provides a new competent toolkit for late-stage peptide modification, labelling, and peptide-drug conjugation and provides a clue for protein bioconjugation.