Deuterium labelling of the GABA agonists THIP, piperidine-4sulphonic acid and the GABA uptake inhibitor THPO

The preparations of deuterium labelled THIP ([7,7-2H]4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-o1)(7) and THPO ([4,4,7-2H]4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-o1) (14) are described. [7,7-2H]-THIP (7) was synthesized by triethylamine catalyzed exchange of hydrogen for deuterium in 3-methoxy-6-nitroso-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine (5) using deuterium oxide, followed by acid catalyzed denitrosation and demethylation. A similar reaction sequence was employed for the preparation of [4,4,7-2H]THPO (14), though the exchange reaction on the N-nitroso intermediate 12 required strongly basic conditions. Deuterium labelled P4S (piperidine-4-sulphonic acid) (17) was synthesized by catalytic deuteration of pyridine-4-sulphonic acid (16). The structures of the deuterated compounds 6, 7, 13, 14, and 17 were established using 1H NMR spectroscopy, in the case of 17 supported by mass spectrometry. (author)