A Proposal for Using Mild Bases in the Preparation of Optically Pure Peptides

Abstract Base catalyzed racemization of N-carbobenzoxy-S-benzyl-l-cysteine p-nitrophenyl ester was studied with various tertiary amines; N, N-dialkylglycine esters and N-ethylmorpholine were found to induce less racemization than triethylamine. Furthermore, these mild bases were strong enough in many cases to liberate free amino acid or peptide esters from their salts. It was also confirmed that a mixture of an amino acid or peptide ester salt and such a mild base could be used in the place of a previously prepared free ester for peptide synthesis, and practically no racemization was observed during the coupling reaction with an acylamino acid active ester. Anderson’s racemization test was also carried out by the mixed anhydride procedure with these mild bases instead of triethylamine; the mild bases were found to give better results in optical purity.