SYNTHESIS OF L-THREO-[1-C-13,2,3-H-2(2)]AMINO-ACID AND L-ERYTHRO-[1-C-13,2,3-H-2(2)]AMINO-ACID - NOVEL PROBES FOR CONFORMATIONAL-ANALYSIS OF PEPTIDE SIDE-CHAINS

An efficient and convenient route for the preparation of L-threo- and L-erythro-[1-C-13,2,3-H-2(2)]amino acids 5 as probes for the conformational analysis of peptide side chains by NMR spectroscopy is described. Stereoselective incorporation of deuterium into the alpha,beta-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 these doubly labelled amino acids, it was possible to obtain vicinal coupling constants between carbonyl carbon and prochiral beta-protons, J(C-13(1)-H-1(beta 1)) and J(C-13(1)-H-1(beta 2)), through C-13 NMR spectroscopy alone. We also demonstrate the determination of the fractional populations of rotamers in respect of the C-alpha-C-beta bond of the amino acids using the measured coupling constants.