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.
Bissel
Philippe
P
Department of Chemistry, Virginia Polytechnic Institute and State University, West Campus Dr., Blacksburg, VA 24061-0212, USA. pbissel@vt.edu
Khalil
Ashraf
A
Rimoldi
John M
JM
Igarashi
Kazuo
K
Edmondson
Dale
D
Miller
Anthony
A
Castagnoli
Neal
N
D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
C528602:3-methyl-6-phenyl-3-aza-bicyclo(4.1.0)heptane; D001643:Bridged Bicyclo Compounds; D008995:Monoamine Oxidase