Studies on the cytochrome P450 catalyzed oxidation of 13C labeled 1-cyclopropyl-4-phenyl-1,2,3,6-tetrahydropyridine by 13C NMR.
A recent study from Hanzlik's laboratory (J. Am. Chem. Soc. 2002, 124, 8268) has provided compelling evidence of a hydrogen atom transfer pathway for the cytochrome P450-catalyzed oxidative N-decyclopropylation of N-cyclopropyl-N-methylaniline. In the present paper, we report an analogous pathway for the oxidative decyclopropylation of a 13C-labeled 1-cyclopropyl-4-phenyl-1,2,3,6-tetrahydropyridinyl substrate. Three 13C-enriched metabolites were characterized: (1) a diastereomeric pair of N-cyclopropyl-N-oxides; (2) the N-cyclopropylpyridinium species; and (3) cyclopropanone hydrate. These results extend the hydrogen atom transfer pathway to include aliphatic tertiary amine substrates. Consideration of all of the available evidence, however, leads us to conclude that the cytochrome P450-catalyzed alpha-carbon oxidations of cyclopropylamines may proceed via both the single electron and hydrogen atom transfer pathways.
Bissel
Philippe
P
Department of Chemistry, Virginia Tech, Blacksburg, VA 24061-0212, USA.
Castagnoli
Neal
N
Penich
Sarah
S
D002247:Carbon Isotopes; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010084:Oxidation-Reduction; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
D002247:Carbon Isotopes; D011725:Pyridines; D003577:Cytochrome P-450 Enzyme System