Synthesis of N-Decanoyl-α-and-γ-Glutamyl Oligopeptide Methyl Esters

A series of N-decanoyl methyl esters of α- and γ-glutamyl oligopeptides including the isomer pairs of ten dipeptides, three tripeptides, and one tetrapeptide, in most of which glutamic acid was at the N-terminal, were prepared for use in a study of the mass spectrometric differentiation of the flutamyl peptide isomers. Z-Glutamyl γ- and α-methyl esters were condensed with amino acid or peptide methyl esters by the mixed anhydride, active ester, or dicyclohexylcarbodiimide method to give Z-α- and γ-glutamyl di-to tetrapeptides (1a-1 and 2a-1), respectively, in reasonable yields. These intermediate peptides were then decarbobenzoxylated by catalytic hydrogenation, followed by coupling with decanoic acid by the mixed anhydrode or active ester method to yield the corresponding N-decanoyl-α- or -γ-glutamyl peptide methyl esters (3a-1 or 4a-1). With essentially the same procedure as above, the isomer pairs of glutaminyl dipeptide and glutamyl tripeptide derivatives (3m-1 and 4m-1) were also prepared.