SYNTHESIS OF (2R)- AND (2S)- -2-AMINO-2-METHYLMALONIC ACID: CHIRAL SUBSTRATES FOR SERINE HYDROXYMETHYLTRANSFERASE

Article abstract of DOI:10.1016/S0040-4020(01)90505-8

(2R)- and (2S)-<1-13C>-2-amino-2-methylmalonate, probes for the stereochemical course of the serine hydroxymethyltransferase reaction, have been synthesised from bis-lactim ethers derived from valine and alanine.Direct acylation of the anion with diethyl carbonate gave the N-ethoxycarbonyl derivative rather than the required ethyl ester.The 13C-labelled carboxyl group was therefore introduced via treatment of the anion with <1-13C>-acetyl chloride, followed by haloform oxidation.The resulting carboxylate salt was then esterified with methyl iodide, and the bis-lactither ring system was cleaved under acidic conditions to give the amino acid esters.Saponification and then separation by cation chromatography gave the title compounds.