CHEMICAL-MODEL STUDIES ON THE MONOAMINE OXIDASE-B CATALYZED OXIDATIONOF 4-SUBSTITUTED 1-METHYL-1,2,3,6-TETRAHYDROPYRIDINES

The MAO-B catalyzed alpha-carbon oxidation of amines has been proposed to proceed via either a single electron transfer (SET) or hydrogen at om transfer (HAT) pathway. In an attempt to distinguish between these pathways, we have examined the alpha-carbon oxidation of a series of 4 -substituted 1-methyl-1,2,3,6-tetrahydropyridine derivatives, compound s which are MAO-B substrates, employing chemical models of the SET pat hway [using the PF6- salt of Fe+3 (1,10-phenanthroline)(3) as the elec tron acceptor] and HAT pathway (using the tert-butoxyl radical as the hydrogen atom acceptor). The rates of oxidation and deuterium isotope effects observed with these compounds were similar with the two model reactions. Consequently, unlike their utility in modeling the related cytochrome P450 catalyzed alpha-carbon oxidation of N,N-dimethylanilin e derivatives, it appears that these reagents will not distinguish bet ween the proposed pathways. (C) 1997 Elsevier Science Ltd.