Synthesis and application of an auxiliary group for chemical ligation at the X-gly site

An efficient synthesis of an auxiliary group, the 2-mercapto-4,5-dimethoxybenzyl (Dmmb) moiety, to form a Gly-building block is presented. The building block was incorporated into peptides to study the reaction with thiobenzyl-activated derivatives. The target peptides have been obtained by standard chemical ligation reaction, followed by TMSBr-assisted cleavage to remove the auxiliary group. Prior to Dmmb removal, under acidic conditions an unexpected rearrangement was observed and evidence for a mechanism is provided.