(2R) - and (2S)-[1-C-13]-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 C-13-labelled carboxyl group was therefore introduced via treatment of the anion with [1-C-13]-acetyl chloride, followed by haloform oxidation. The resulting carboxylate salt was then esterified with methyl iodide, and the bis-lactim ether ring system was cleaved under acidic conditions to give the amino acid esters. Saponification and then separation by cation exchange chromatography gave the title compounds.
Thomas, N. R. (1991). Synthesis of (2R)- (2S)- [1-13C]-2-amino-2-methylmalonic acid: chiral substrates for serine hydroxymethyltransferase. Tetrahedron, 47(3), 497–506.