Methyl L-phenylalaninate hydrochloride → HCID 7155221, compound

Participants

Reaction Steps

Having shown the removability of 1 and its derivatives from organic solvents, we next demonstrate its effectiveness as a peptide coupling reagent and general dehydrating agent. Coupling CBZ-Ala (10) and Phe-OMe.HCl in THF with HOBT and 1 afforded CBZ-Ala-Phe-OMe (21) in 84% yield. Using DMF as the solvent, the yield increased to 93%. The more hindered coupling of BOC-Ile (26) and Phe-OMe.HCl with HOBT and 1 produced yields of 82% and 85% of BOC-Ile-Phe-OMe (26) in THF and DMF, respectively. In all cases there was no racemization, as would be expected from N-carbamate-protected amino acids. The 1/HOBT mediated C-terminus coupling of CBZ-Ala-Phe (11) with Gly-OBn.TsOH in DMF produced CBZ-Ala-Phe-Gly-OBn (27) in which the Phe was racemized to the extent of 0.68% after 4 h and 1.3% after 20 h, consistent with similar experiments using DCC and EDC. The same coupling carried out in the presence of 50 mol % of anhydrous CuCl2 gave racemization-free 27, even after reactions were allowed to proceed for 20 h at room temperature. These results were also in agreement with literature data. (Miyazawa et al., Int. J. Peptide & Protein Res., 39, p. 237 (1992); Miyazawa et al., Int. J. Peptide & Protein Res., 39, p. 308 (1992).) In each case, all residual 1 and urea by-products 3 were easily removed from the reaction mixtures with a simple acid wash.

Provenance & Evidence