ENANTIOSELECTIVE SYNTHESES OF ISOTOPICALLY LABELED ALPHA-AMINO-ACIDS - PREPARATION OF SPECIFICALLY C-13-LABELED L-LYSINES

[2-C-13]-L-lysine, [3,4-C-13(2)]-L-lysine and [5,6-C-13(2)]-L-lysine a re prepared from simple, commercially available, highly enriched start ing materials as [2-C-13]-glycine, ethyl [1,2-C-13(2)]-bromo acetate, and [1,2-C-13(2)]-acetonitrile. The introduction of the chiral center is based on a general method starting from the bis-lactim ether of cyc lo-(D-Val-Gly). The synthesis of C-13]-3,6-diethoxy-2,5-dihydro-2-isop ropylpyrazine is described. The availability of our method for the pre paration of specifically enriched bis-lactim ethers allows the synthes is of a great variety of site specific isotopically labelled (L- and D -) alpha-amino acids. Moreover, intermediate -3,6-diethoxy-2,5-dihydro -2-isopropyl-5-pyrazinyl] butyronitrile is a valuable precursor in the synthesis of L-alpha-aminoadipic acid. The synthetic scheme in this p ublication makes both L-lysine and L-alpha-aminoadipic acid C-13- Or N -15-labelled at any position, easily available. The isotopomers of lys ine are obtained on a preparative scale in good yields, with 99% C-13 and high enantiomeric purity (>97% e.e.). Three isotopomers are charac terized using various spectroscopic techniques, e.g., H-1 NMR, C-13 NM R and Mass spectrometry.