Syntheses of (2S,3R)- and (2S,3S)-3-methylglutamic acid

Abstract

Arndt–Eistert homologation of suitably protected (2S, 3S)-3-methylaspartic acid occurs with retention of configuration at C-3 to give, ultimately, (2S, 3R)-3-methylglutamic acid. (2S, 3R)-3-Methylglutamic acid was also prepared in good yield via the conjugate addition of the lithiated anion of the bis-lactim ether of cyclo-(R-Val -Gly) to methyl (E)-butenoate. The analogous reaction performed using isopentyl (Z)-butenoate ultimately gave (2S, 3S)-3-methylglutamic acid. Both conjugate addition occurs with high diastereoselectivity.