Selective modification of tryptophan in polypeptides C-N coupling with azoles using -generated iodine-based oxidants in aqueous media

This study demonstrates the C-N coupling of tryptophan with azoles, promoted by an in situ -generated iodine-based oxidant. The protocol was successfully applied to the selective modification of tryptophan in nonprotected polypeptide bearing oxidatively sensitive residues in acidic aqueous media. The present method allows the attachment of reactive handles to polypeptides and the peptide stapling. Hypervalent iodine-mediated C-N coupling of the indole and azoles realizes the selective modification of tryptophan in polypeptides in aqueous media. The process allows the introduction of chemical handles and the peptide stapling.