Synthesis ofL-threo- andL-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(13C1–1Hβ1) and J(13C1–1Hβ2), through 13C NMR spectroscopy alone. We also demonstrate the determination of the fractional populations of rotamers in respect of the Cα–Cβ bond of the amino acids using the measured coupling constants.