Synthesis of (2S,4S)- and (2S,4R)-5,5′-dihydroxy[5,5-2H2]leucine by two independent routes

Abstract

In studies directed at discovering the absolute stereochemistry of the reaction catalysed by the enzyme glutamate γ-carboxylase, two independent stereoselective syntheses of (2S,4S)-5,5′-dihydroxy[5,5-²H₂]-leucine 4a and its (2S,4R)-diastereoisomer 4b have been developed. The first synthesis uses (2S)-pyroglutamic acid as starting material and provides (2S,4S)-5,5′-dihydroxy[5,5-²H₂]leucine 4a, while the second starts with (2S,4R)-4-hydroxyproline and provides (2S,4R)-5,5′-dihydroxy[5,5-²H₂]leucine 4b.