Versatile synthesis of stereospecifically labelled D-amino acids via labelled aziridines—preparation of (2R,3S)-[3-2H1]- and (2R,3R)-[2,3-2H2]-serine; (2S,2′S,3S,3′S)-[3,3′-2H2]- and (2S,2′S,3R,3′R)-[2,2′,3,3′-2H4]-cystine; and (2S,3S)-[3-2H1-] and (2S,3R)-[2,3-2H2]-β-chloroalanine

Abstract

Stereospecifically β-labelled protected 2-carboxyaziridines 2, with the stereochemistry of a D-amino acid at C-2, have been prepared by a chemicoenzymic synthesis. Preparation of the labelled malates 5, by hydration of fumaric acid using the enzyme fumarase or by amination with aspartase followed by nitrosation, was followed by conversion into the isoserines 3, by a process involving Curtius rearrangement with retention of stereochemistry at the chirally labelled primary centre. Protection and ring closure gave the aziridines 2, which, on ring opening with the appropriate nucleophiles and deprotection, gave stereospecifically labelled samples of D-serine 16, D-Cystine 20 and β-chloro-D-alanine 22.