4-Methoxybenzyloxymethyl group as an Nπ-protecting group for histidine to eliminate side-chain-induced racemization in the Fmoc strategy

The 4-methoxybenzyloxymethyl (MBom) group was introduced at the Nπ-position of histidine, and its utility was examined under the conditions for peptide synthesis by Fmoc strategy. The Nπ-MBom group proved to prevent the risk of racemization during incorporation of the His residue and to possess all of the chemical properties required for Fmoc chemistry. The side reaction associated with formaldehyde generated from the Nπ-MBom group upon acidolysis could be effectively prevented by performing the standard TFA treatment in the presence of methoxyamine·hydrochloride (MeONH2·HCl).