STUDIES ON THE OXIDATION OF 1,4-DISUBSTITUTED-1,2,3,6-TETRAHYDROPYRIDINES

Abstract

Interest in the parkinsonian-inducing proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine has prompted extensive studies into the oxidative pathways mediating its bioactivation to the corresponding pyridinium species, a potent inhibitor of the mitochondrial electron transport chain. The initial step in the overall reaction is the two-electron ring α-carbon oxidation to give the 1-methyl-4-phenyl-2,3-dihydropyridinium species, a reaction that is catalyzed by monoamine oxidase B. The same α-carbon oxidation is catalyzed by members of the cytochrome P-450 family of oxidases. This paper examines the impact that various structural features of 1,4-disubstituted-1,2,3,6-tetrahydropyridinyl derivatives have on the oxidative fate of this class of compound.

Key Words :

• Monoamine oxidase
• Cytochrome P450
• α-Carbon oxidation of cyclic tertiary amines
• Single electron transfer
• Hydrogen atom transfer