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

Philippe Bissel; Ashraf Khalil; John M Rimoldi; Kazuo Igarashi; Dale Edmondson; Anthony Miller; Neal Castagnoli Jr

doi:10.1016/j.bmc.2008.02.014

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

Bioorg Med Chem. 2008 Apr 1;16(7):3557-64. doi: 10.1016/j.bmc.2008.02.014. Epub 2008 Feb 8.

Authors

Philippe Bissel¹, Ashraf Khalil, John M Rimoldi, Kazuo Igarashi, Dale Edmondson, Anthony Miller, Neal Castagnoli Jr

Affiliation

¹ Department of Chemistry, Virginia Polytechnic Institute and State University, West Campus Dr., Blacksburg, VA 24061-0212, USA. pbissel@vt.edu

PMID: 18313306
DOI: 10.1016/j.bmc.2008.02.014

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bridged Bicyclo Compounds / chemical synthesis*
Bridged Bicyclo Compounds / chemistry
Bridged Bicyclo Compounds / metabolism*
Magnetic Resonance Spectroscopy
Molecular Structure
Monoamine Oxidase / metabolism*
Stereoisomerism
Structure-Activity Relationship
Substrate Specificity

Substances

3-methyl-6-phenyl-3-aza-bicyclo(4.1.0)heptane
Bridged Bicyclo Compounds
Monoamine Oxidase