Synthesis of trimethyl (2S,3R)- and (2R,3R)-[2-2H1]-homocitrates and dimethyl (2S,3R)- and (2R,3R)-[2-2H1]-homocitrate lactones—an assay for the stereochemical outcome of the reaction catalysed both by homocitrate synthase and by the Nif-V protein

Abstract

Trimethyl (3R)-homocitrate 17, trimethyl (2S,3R)-[2-²H₁]-homocitrate 17a and (2R,3R)-[2-²H₁]-homocitrate 17b, as well as dimethyl (3R)-homocitrate lactone 18, (2S,3R)-[2-²H₁]-homocitric lactone 18a and (2R,3R)-[2-²H₁]-homocitric lactone 18b have been synthesised. D-Quinic acid 12 was used as the source of the (3R)-centre in the unlabelled target compounds 17 and 18. (−)-Shikimic acid 19 and the (−)-[2-²H]-shikimic acid derivative 32 respectively were used in the synthesis of the labelled compounds. In the latter syntheses, Sharpless directed epoxidation of the olefin in the 5-deoxy ester diols 23 and 35 ensured a reaction from the same face as the allylic and homoallylic alcohols, and the reduction of the protected epoxides 25 and 37 ensured that the label was introduced in a stereoselective manner. The ¹H NMR spectra of the labelled products present an assay for the stereochemistry of the biological reactions catalysed by homocitrate synthase and by the protein from the nifV gene.