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

摘要

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 -position of the side chain, were obtained by enzymatic coupling of the corresponding halogenated derivatives of indole with S-methyl-l-cysteine in (H2O)-H-2, catalysed by enzyme tryptophanase (EC 4.1.99.1). The positional deuterium enrichment of the resulting tryptophan derivatives was controlled using H-1 NMR. In accordance with the mechanism of the lyase reaction, a 100% deuterium labelling was observed in the -position; the chemical yields were between 23 and 51%. Furthermore, -F-l-alanine, synthesized from -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 (approximate to 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.