Synthesis of L-threo- and L-erythro-amino acids: novel probes for conformational analysis of peptide side chains
An efficient and convenient route for the preparation of L-threo- and L-erythro-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 deuteration of dehydroamino acid derivatives 1 and 2 followed by a combination of enzymic optical resilution and the racemization at the 2-position.Using these doubly labelled amino acids, it was possible to obtain vicinal coupling constants between carbonyl carbon and prochiral β-protons, J(13C-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.