L-[4-(13)C]Glutamine was synthesized from sodium [2-(13)C]acetate in 12 steps and 18% overall yield. A Wittig reaction of (R)-benzyl 4-formyl-2,2-dimethyloxazolidine-3-carboxylate and ethyl 2-(triphenylphosphoranylidene)[2-(13)C]acetate prepared from D-serine and sodium [2-(13)C]acetate, respectively, gave (4S)-4-(2-ethoxycarbonyl[2-(13)C]vinyl)-2,2-dimethyloxazolidine-3-carboxylic acid α,β-isopropylidene group, oxidation of the resulting hydroxyl group to a carboxyl group and transamidation of the ester moiety gave L-N-Cbz-[4-(13)C]glutamine (Cbz = benzyloxycarbonyl). Finally, removal of the Cbz group gave L-[4-(13)C]glutamine. L-[4-(13)C]Glutamine can be prepared in fewer steps and higher yield by this method compared with previously reported methods.
Keywords: C-13; Wittig reaction; amino acid; glutamine; serine; stable labeled synthesis.
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