Stereochemical studies on the novel monoamine oxidase B substrates (1R,6S)- and (1S,6R)-3-methyl-6-phenyl-3-aza-bicyclo[4.1.0]heptane

Previous studies have established the unexpected monoamine oxidase-B (MAO-B) substrate properties of racemic 3-methyl-6-phenyl-3-aza-bicyclo[4.1.0]heptane, the 3,4-cyclopropyl analog of the achiral proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The two stereocenters present in this compound provide an opportunity to examine the enantioselectivity and diastereoselectivity of the MAO-B-catalyzed ring alpha-carbon oxidation of cyclic tertiary amines to give the corresponding conjugated iminiumyl metabolites. This paper reports the results of such stereochemical studies using expressed human MAO-B as the catalyst.