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

Article abstract of DOI:10.1016/S0040-4039(97)00164-0

The enantioselective synthesis of [¹⁵N]-L-allothreonine 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, [¹⁵N]-(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.