Chemical model studies on the monoamine oxidase-B catalyzed oxidation of 4-substituted 1-methyl-1,2,3,6-tetrahydropyridines

Abstract

The MAO-B catalyzed α-carbon oxidation of amines has been proposed to proceed via either a single electron transfer (SET) or hydrogen atom transfer (HAT) pathway. In an attempt to distinguish between these pathways, we have examined the α-carbon oxidation of a series of 4-substituted 1-methyl-1,2,3,6-tetrahydropyridine derivatives, compounds which are MAO-B substrates, employing chemical models of the SET pathway [using the PF 6 − salt of Fe +3 (1,10-phenanthroline) 3 as the electron 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 α-carbon oxidation of N, N-dimethylaniline derivatives, it appears that these reagents will not distinguish between the proposed pathways.