Kinetic Studies in Peptide Chemistry. Coupling, Racemization, and Evaluation of Methods Useful for Shortening Coupling Time

Article abstract of DOI:10.1021/jo01294a029

Kinetic studies were carried out on N-protected methionine and glycylmethionine active esters to determine the racemization rate constants with triethylamine and the coupling rate constants with valine methyl ester.In contrast to cysteine dipeptide active esters, which racemize through an enolization mechanism, the methionine dipeptide active esters racemize through the usual 5(4H)-oxazolone route.The role of sulfur in the side chain is discussed.The time required for coupling a given percentage (e.g., 99 percent) of the amine component can be significantly reduced by using an excess of the active ester.This method is evaluated quantitatively for second-order kinetics.