3-Nitro-2-Pyridinesulfenyl Group for Protection and Activation of the Thiol Function of Cysteine

The use of the 3-nitro-2-pyridinesulfenyl (Npys) halide, a versatile reagent in peptide chemistry, for the protection and activation of the thiol function is reported. Boc-Cys(Npys)–OH is prepared starting from bis(N-t-butyloxycarbonyl)-l-cystine. The Npys group is easily removed by treatment with a stoichiometric amount of tri-n-butylphosphine in the presence of water, but it is resistant to acids such as trifluoroacetic acid, HCl, and HF. Importantly, the cysteine residue modified with the Npys group can react selectively with free thiol of cysteine to afford a cystine disulfide bond.