Novel synthesis of optically active γ-carboxyglutamic acid and its derivatives

A novel synthesis of optically active L-γ-carboxyglutamic acid (GLA), found in prothrombin and other vitamin K-dependent factors, is described. This method involves the formation of γ-carbanion of the protected glutamic acid esters by means of a non-nucleophilic base, followed by the treatment with benzyl chloroformate or other electrophilic agents, and deprotection by hydrogenation or hydrolysis. This convenient technique is potentially useful for preparation of not only the γ-carboxyglutamic acid itself, but also of the mixed protected ester and amino functions for further peptide syntheses containing this amino acid.