Catalysis in peptide synthesis with active esters. II. Effects of concentrated carboxylic acids on the aminolysis of benzyloxycarbonyl-L-phenylalanine p-nitrophenyl ester in dioxane.

Abstract

Abstract The kinetics of the aminolysis reaction of benzyloxycarbonyl-l-phenylalanine p-nitrophenyI ester with glycine t-butyl ester in dioxane were studied in the presence of high concentrations of several carboxylic acids. Bell-shaped curves were obtained when the rate constants observed for the trimethylacetic acid-, acetic acid-, and monochloroacetic acid-catalyzed reactions were plotted against the logarithms of the reciprocals of the acid concentrations. Cyanoacetic acid and trichloroacetic acid did not accelerate, but, rather, retarded the reaction. In the mathematical derivation the catalyst apparently exhibits no accelerating effect, if k0K>kcat, where k0 and kcat are the uncatalyzed and the true catalyzed rate constants respectively, and where K is the acidbase equilibrium constant between the nucleophile and the catalyst in a given solvent. The true catalyzed rate constants, kcat, from which the effect of the protonation of the nucleophile had been eliminated were estimated for the trimethylacetic acid- and acetic acid-catalyzed reactions. The fact that the kcat value (63m−2 min−1) for trimethylacetic acid, the weaker acid, was greater than that (53m−2 min−1) for acetic acid strongly supports the bifunctional, concerted mechanism presented in the preceding paper.