Oxidative Deblocking of the 4‐Methoxybenzyl Thioether Protecting Group: Application to the Directed Synthesis of Poly‐cystinyl Peptides

Abstract

AbstractThe 4‐methoxybenzyl thioether protecting group is deblocked efficiently by oxidation with the homogeneous electron transfer agent tris(4‐bromophenyl)ammoniumyl (2.⊕) leading to the disulfide in high yields. S‐(4‐methoxybenzyl)cysteine derivatives like 9 in this way can be transformed into the corresponding cystine derivatives like 10 in 90% yield. Many N and carboxy protecting groups like the Boc and Z group and tert‐butyl or benzyl ester functions are stable under the cleavage conditions. On the other hand the 4‐methoxybenzyl thioether protecting group is totally unaffected by the conditions for oxidative deblocking of the S‐trityl functions by either iodine or rhodanolysis. This opens up new opportunities for the directed synthesis of cystinyl peptides with more than one intra‐ or interchain disulfide bridge. Application of the new method to the synthesis of a cystine peptide with one intrachain SS‐bridge and a double‐chain biscystinyl peptide is reported.