Summary
[2-13C]-L-lysine, [3,4-13C2]-L-lysine and [5,6-13C2]-L-lysine are prepared from simple, commercially available, highly enriched starting materials as [2-13C]-glycine, ethyl [1,2-13C2]-bromo acetate, and [1,2-13C2]-acetonitrile. The introduction of the chiral center is based on a general method starting from the bis-lactim ether of cyclo-(D-Val-Gly). The synthesis of (2R)-[5-13C]-3,6-diethoxy-2,5-dihydro-2-isopropylpyrazine is described. The availability of our method for the preparation of specifically enriched bis-lactim ethers allows the synthesis of a great variety of site specific isotopically labelled (L- and D-)α-amino acids. Moreover, intermediate 4-[(2R,5S)-3,6-diethoxy-2,5-dihydro-2-isopropyl-5-pyrazinyl]butyronitrile is a valuable precursor in the synthesis of L-α-aminoadipic acid. The synthetic scheme in this publication makes both L-lysine and L-α-aminoadipic acid13C- or15N-labelled at any position, easily available. The isotopomers of lysine are obtained on a preparative scale in good yields, with 99%13C and high enantiomeric purity (>97% e.e.). Three isotopomers are characterized using various spectroscopic techniques,e.g.,1H NMR,13C NMR and Mass spectrometry.
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Raap, J., Wolthuis, W.N.E., Hehenkamp, J.J.J. et al. Enantioselective syntheses of isotopically labelledα-amino acids Preparation of specifically13C-labelled L-lysines. Amino Acids 8, 171–186 (1995). https://doi.org/10.1007/BF00806490
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DOI: https://doi.org/10.1007/BF00806490