Visible-Light-Driven Synthesis of Ketonyl Cysteine Compounds by Cysteine Decysteinylation with Enol Silyl Ethers Coupling

A facile method for the synthesis of stereochemically well-defined ketonyl cysteine compounds has been established. This was achieved via an N-phenylphenothiazine-photocatalyzed, radical-based desulfurative addition, using the in situ-generated tetrafluoropyridyl cysteine derivative from the thiol as a key precursor, which ensures high retention of configuration. Notably, this method features simple operation: the phenothiazine photosensitizer employed in the reaction is inexpensive and readily available in comparison with costly iridium catalysts. It also boasts the advantages of easily accessible starting materials, mild reaction conditions, excellent functional group tolerance, high stereoretention, and good yields, thus exhibiting broad applicability in the modification of complex peptide molecules.