Syntheses of halogen derivatives of L-tryptophan, L-tyrosine and L-phenylalanine labeled with hydrogen isotopes

Halogenated, labeled with tritium and doubly with deuterium and tritium, derivatives of L-tryptophan, i.e. 5-bromo-[2-H-3]-, 5-bromo-[2-H-2/H-3]-, 5-fluoro-[2-H-3]-5-fluoro-[2-H-2/H-3]-, 6-fluoro-[2-H-3]-, 6-fluoro-[2-H-2/H-3]-L-tryptophan, as well as, L-tyrosine, i.e. 3-fluoro-[2-H-3]-, 3-fluoro-[2-H-2/H-3]-, 3-chloro-[2-H-3]-, and 3-chloro-[2-H-2/H-3]-L-tyrosine, and also L-phenylalanine, i.e. 2-fluoro-[(3S)-H-3]-, 2-fluoro-[(3S)-H-2/H-3]-, 2-chloro-[(3S)-H-3]-, 2-chloro-[(3S)-H-2/H-3]-, 4-chloro-[(3S)-H-3]-, and 4-chloro-[(3S)-H-2/H-3]-L-phenylalanine were synthesized using enzymatic methods. Isotopomers of L-tryptophan were synthesized by coupling of halogenated indoles with S-methyl-L-cysteine carried out in deuteriated or tritiated incubation media. Labeled halogenated derivatives of L-tyrosine were obtained by the enzymatically supported exchange between halogenated L-tyrosine and isotopic water. Labeled halogenated isotopologues of L-Phe were synthesized by the enzymatic addition of ammonia to halogenated cinnamic acid. As a source of hydrogen tritiated water (HTO) and heavy water (D2O) with addition of HTO were used.