Synthesis of deuterium-labelled halogen derivatives of L-tryptophan catalysed by tryptophanase

The isotopomers of halogen derivatives of l-tryptophan (l-Trp) (4′-F-, 7′-F-, 5′-Cl- and 7′-Br-l-Trp), specifically labelled with deuterium in α-position of the side chain, were obtained by enzymatic coupling of the corresponding halogenated derivatives of indole with S-methyl-l-cysteine in ²H₂O, catalysed by enzyme tryptophanase (EC 4.1.99.1). The positional deuterium enrichment of the resulting tryptophan derivatives was controlled using ¹H NMR. In accordance with the mechanism of the lyase reaction, a 100% deuterium labelling was observed in the α-position; the chemical yields were between 23 and 51%. Furthermore, β-F-l-alanine, synthesized from β-F-pyruvic acid by the l-alanine dehydrogenase reaction, has been tested as a coupling agent to obtain the halogenated deuterium-labelled derivatives of l-Trp. The chemical yield (～30%) corresponded to that as observed with S-methyl-l-cysteine but the deuterium label was only 63%, probably due to the use of a not completely deuterated incubation medium.