Synthesis and biological evaluation of p,p'-dideuteriophenytoin

A reaction sequence is described to synthesize p,p'-dideuteriophenytoin in three steps from commercially available starting materials. The deuterium content at best reached 99.2% as measured by mass spectrometry. For materials with isotopic content up to 95%, excellent agreement was found between the data obtained by mass spectrometry and 13C-nuclear magnetic resonance operated in a NOE-suppression mode. p,p'-Dideuteriophenytoin was evaluated comparatively with phenytoin and p-deuteriophenytoin in the maximal electroshock test. While all three compounds exhibited a high degree of antiepileptic activity, none of them demonstrated significant superiority over the others. (author)