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Enantioselective synthesis of isotopically labelled L‐α‐amino acids preparation of 13 C‐, 18 O‐and 2 H‐labelled L‐serines and L‐threonines

1995; Wiley; Volume: 36; Issue: 11 Linguagem: Inglês

10.1002/jlcr.2580361108

1099-1344

Willem F. J. Karstens, H. J. F. F. Berger, E. R. Van Haren, Johan Lugtenburg, Jan Raap,

Cancer, Hypoxia, and Metabolism

Abstract [3‐ 18 O]‐L‐serine, [3‐ 13 C]‐L‐serine, [3‐ 18 O]‐L‐threonine, [3,4‐ 13 C 2 ]‐L‐threonine and [3‐ 2 H]‐L‐threonine are prepared from simple commercially available, isotopically enriched starting materials like H 2 18 O, [ 13 C]‐paraformaldehyde, [ 13 C 2 ]‐acetaldehyde and [1‐ 2 H]‐acetaldehyde. The introduction of the side chain is based on the reaction of the anion of the bislactimether of cyclo‐(D‐Val‐Gly) with a suitable reagent. For serine this is isotopically labelled benzylchloromethylether, whereas for threonine labelled acetaldehyde is used in combination with chlorotitaniumtris[diethylamide], introducing both stereocentres in one single step. The isotopomers of serine and threonine are obtained on the gram scale in good yields and high enantiomeric and diasteriomeric excesses. New syntheses for [ 18 O]‐benzylalcohol and isotopically enriched benzylchloromethylether are reported. Following the presented synthetic scheme these amino acids can be labelled at any position or at any combination of positions.