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SummaryMonoamine oxidase B metabolizes I-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 1) first to l-methyl-4-phenyl-2,3-dihydropyridinium salt (MPDP+; 5), and then to 1-methyl-4-phenylpyridinium salt (MPP+; 7). Chemical synthesis of MPDP+ and its 5-methyl analog 6 was accomplished from the N-oxides 3 and 4 of MPTP and its 5-methyl analog, respectively, by a Polonovski reaction. Oxidation of MPDP' to MPP+ was accomplished with air, and greatly accelerated by Pt catalyst. Reduction of MPDP' and MPP' with NaBH, afforded MPTP.The compound l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP; 1) [I] was found to be highly neurotoxic in man and certain animal species, depleting the substantia nigra of dopamine and causing effects similar to those observed in Parkinson's disease [2-51. The pyridinium salt 7 (MPP'), isolated from brain tissue of monkey and characterized by HPLC/MS, is considered to be the major metabolite of MPTP in human and primates [&8].The 5-methyl derivative 2 was included in this investigation since it is closly related to analgetics of the prodine family of drugs [9].Chemistry. -In this communication we report the facile chemical conversion of MPTP (1) and its 5-methyl derivative 2 [9] to their pyridinium analoges 7 and 8, respectively, via dihydropyridinium salts 5 and 6. Although oxidation of tetrahydropyridines to pyridines can be accomplished directly using mercury acetate [lo], we considered the approach via dihydropyridinium derivatives to be more 'physiological' since the 1 -methyl-4-phenyl-2,3-dihydropyridinium salt (5, MPDP+) is a likely intermediate metabolite of MPTP [7] [8]. The methodology applied for conversion of tetrahydropyridines to dihydropyridinium salts was based on the Polonovski reaction utilized successfully ') ' ) Dedicated to Prof. Dr. H . C. Beyerrnun of the Laboratory of Organic Chemistry at the Technical Highschool in Delft, the Netherlands, on the occasion of his 65th birthday. Visiting scientist from A.