Preparation of Protected α-Methoxyglycine and Its Incorporation into Peptide Synthesis

A protected α-methoxyglycine Cbz-DL-Gly(OMe)-OMe (1) was prepared from the N-chloro derivative of Cbz-Gly-OMe. Catalytic hydrogenolysis of 1 in the presence of a mixed anhydride prepared from a Boc-amino acid and ClCO2Bui gave a diastereomeric protected dipeptide containing the Gly(OMe) residue. The dermorphin analogs L-Tyr-D/L-Gly(OMe)-L-Phe-Gly-NH2 were synthesized.