Synthesis of L-threo- and L-erythro-[1-13C, 2,3-2H2]amino acids: novel probes for conformational analysis of peptide side chains

Abstract

An efficient and convenient route for the preparation of L-threo- and L-erythro-[1-^l3C, 2,3-²H₂]amino acids 5 as probes for the conformational analysis of peptide side chains by NMR spectroscopy is described. Stereoselective incorporation of deuterium into the α,β-positions of amino acid 5 was accomplished by catalytic deuteriation of dehydroamino acid derivatives 1 and 2 followed by a combination of enzymic optical resolution and the racemization at the 2-position. Using the doubly labelled amino acids, it was possible to obtain vicinal coupling constants between carbonyl carbon and prochiral β-protons, J(¹³C¹–¹H^β1) and J(¹³C¹–¹H^β2), through ¹³C NMR spectroscopy alone. We also demonstrate the determination of the fractional populations of rotamers in respect of the C^α–C^β bond of the amino acids using the measured coupling constants.