Amino Acids and Peptides. VI. Novel Peptide Bond Formation catalyzed by Metal Ions. IV. Formation of optically Active Amino Acid Amides and Peptide Amides

Abstract

The Cu (II)-catalyzed peptide bond formation previously reported by us, was applied to the synthesis of optically active amino acid amides and peptide amides.
Treatment of an optically active amino acid ester with a primary amine in the presence of anhydrous CuCl₂ afforded the desired amino acid secondary amide, without racemization, in 60-70% yield. However, the same reaction with a secondary amine with larger steric hindrance than primary amine gave an optically active tertiary amide in a very low yield as expected from the proposed mechanism. Almost all the amino acid amides could be isolated as hydrochlorides or as free bases.
Some peptide amides, i. e. Z-Gly-Gly-NH-Bzl, and Z-Ala-Gly-NH-Bzl, were also prepared.