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‐ 3 H]‐, 5′‐bromo‐[2‐ 2 H/ 3 H]‐, 5′‐fluoro‐[2‐ 3 H]‐5′‐fluoro‐[2‐ 2 H/ 3 H]‐, 6′‐fluoro‐[2‐ 3 H]‐, 6′‐fluoro‐[2‐ 2 H/ 3 H]‐ L ‐tryptophan, as well as, L ‐tyrosine, i.e. 3′‐fluoro‐[2‐ 3 H]‐, 3′‐fluoro‐[2‐ 2 H/ 3 H]‐, 3′‐chloro‐[2‐ 3 H]‐, and 3′‐chloro‐[2‐ 2 H/ 3 H]‐ L ‐tyrosine, and also L ‐phenylalanine, i.e. 2′‐fluoro‐[( 3S) ‐ 3 H]‐, 2′‐fluoro‐[ (3S) ‐ 2 H/ 3 H]‐, 2′‐chloro‐[ (3S)‐ 3 H]‐, 2′‐chloro‐[ (3S)‐ 2 H/ 3 H]‐, 4′‐chloro‐[ (3S)‐ 3 H]‐, and 4′‐chloro‐[ (3S)‐ 2 H/ 3 H]‐ 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 (D 2 O) with addition of HTO were used.