title: Enantioselective syntheses of isotopically labelledα-amino acids Preparation of specifically(13)C-labelled L-lysines.
abstract: [2-(13)C]-L-lysine, [3,4-(13)C2]-L-lysine and [5,6-(13)C2]-L-lysine are prepared from simple, commercially available, highly enriched starting materials as [2-(13)C]-glycine, ethyl [1,2-(13)C2]-bromo acetate, and [1,2-(13)C2]-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-(13)C]-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 acid(13)C- or(15)N-labelled at any position, easily available. The isotopomers of lysine are obtained on a preparative scale in good yields, with 99%(13)C and high enantiomeric purity (>97% e.e.). Three isotopomers are characterized using various spectroscopic techniques,e.g.,(1)H NMR,(13)C NMR and Mass spectrometry.
authors.affiliation: Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, NL-2300, Leiden, RA, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Raap
authors.forename: W N
authors.initials: WN
authors.lastname: Wolthuis
authors.forename: J J
authors.initials: JJ
authors.lastname: Hehenkamp
authors.forename: J
authors.initials: J
authors.lastname: Lugtenburg