Enantioselective syntheses of α-amino-β-hydroxy acids, [formula omitted] and [ 15N]-L-threonine

Abstract

The enantioselective synthesis of [ 15 N]- L-allo threonine from ethyl ( S)-lactate via methyl ( S)-3-methoxymethoxy-2-oxobutanoate 15 is described. The stereogenic centre at C-2 was established by a one-pot, dual enzyme catalysed hydrolysis of the ester (by a lipase) and reductive amination of the ketone of 15 (with leucine dehydrogenase) to give, after deprotection, [ 15 N]-(2S,3S)-2- amino-3-hydroxybutanoic acid as a single diastereomer in 93% yield. [ 15N]-L-Threonine was prepared by an analogous strategy from methyl ( R)-lactate using phenylalanine dehydrogenase in the reductive amination step. This approach may be simply adapted for the incorporation of deuterium and carbon-13.