Asymmetric Synthesis of α-Methylglutamic Acid and α-Methylornithine by a Chiral Isocyano Amide Reagent

Abstract

An efficient approach to the asymmetric syntheses of a-methylglutamic acid and α-methylornithine is described. Two chiral reagents, (2'S)-N-(2'-methoxymethylpyrrolidine)-2-isocyanopropionamide 4 and (2'S)-N-(2'-hydroxymethylpyrrolidine)-2-isocyanopropionamide 5, were employed for the asymmetric induction. α-Methylglutamic acid 7 was synthesized by the asymmetric Michael-addition of methyl acrylate to 4 and 5 as the key step. The optical yield of 7 was 10-45% (R-form). α-Methylornithine 12 was also synthesized by the reaction of 4 with acrylonitrile as the key step. The optical yield of 12 was 31.7% (R-form).