β-Amino acid isomers of a natural substrate of the enzyme γ-glutamyl-amino acid cyclotransferase. Synthesis of (3S)-3-aminoglutaryl-(S)-alanine and (3R)-3-aminoglutaryl-(S)-alanine

Abstract

(3S)-3-Aminoglutaryl-(S)-alanine (8) and (3R)-3-aminoglutaryl-(S)-alanine (14), β-amino acid isomers of the dipeptide γ-glutamyl-(S)-alanine, a natural substrate of the enzyme γ-glutamyl-amino acid cyclotransferase, have been synthesized by two different routes for studies of the enzyme. The better route allowed compounds (8) and (14) to be prepared in diastereoselective sequences from the common intermediate, methyl hydrogen (3S)-3-benzyloxycarbonylaminoglutarate (4); (3S)-3-aminoglutaryl-(S)-alanine (8) by direct coupling of the half acid (4) to (S)-alanine followed by deprotection, and (3R)-3-aminoglutaryl-(S)-alanine (14) by a similar reaction sequence that also included an initial chemical reversal of the acid and ester ends, thereby ‘inverting’ the configuration at C-3, of the glutarate component.