ENANTIOSELECTIVE SYNTHESIS OF ISOTOPICALLY LABELED L-ALPHA-AMINO ACIDS PREPARATION OF C-13-LABELED, O-18-LABELED AND H-2-LABELED L-SERINES AND L-THREONINES

[3-O-18]-L-serine, [3-C-13]-L-serine, [3-O-18]-L-threonine, [3,4-C-13( 2)]-L-threonine and [3-H-2]-L-threonine are prepared from simple comme rcially available, isotopically enriched starting materials like (H2O) -O-18, [C-13]-paraformaldehyde, [C-13(2)]-acetaldehyde and [1-H-2]-ace taldehyde. The introduction of the side chain is based on the reaction of the anion of the bislactimether of cyclo-(D-Val-Gly) with a suitab le reagent. For serine this is isotopically labelled benzylchloromethy lether, whereas for threonine labelled acetaldehyde is used in combina tion with chlorotitaniumtris[diethylamide], introducing both stereocen tres in one single step. The isotopomers of serine and threonine are o btained on the gram scale in good yields and high enantiomeric and dia steriomeric excesses. New syntheses for [O-18]-benzylalcohol and isoto pically enriched benzylchloromethylether are reported. Following the p resented synthetic scheme these amino acids can be labelled at any pos ition or at any combination of positions.