Regio- and stereochemical studies on the alpha-carbon oxidation of (S)-nicotine by cytochrome P-450 model systems.
Results from previous studies indicate that rabbit liver microsomal cytochrome P-450 catalyzes the C-5' two-electron oxidation of (S)-nicotine stereoselectivity with preferential loss of the pro-(E)-hydrogen atom trans to the pyridine ring. We now have examined the regio- and stereochemical features of the oxidation of (S)-nicotine by peroxides in the presence of various hemoproteins and by electrochemical and photochemical methods. None of these systems gave rise to the stereochemical outcomes observed with the cytochrome P-450 mediated reaction. The results of these studies are interpreted as additional evidence for the formation of a highly ordered complex between (S)-nicotine and cytochrome P-450 that directs the regio- and diasterioselective alpha-carbon oxidation of this substrate.
Peterson
L A
LA
Division of Toxicology, School of Pharmacy, University of California, San Francisco 94143.
Castagnoli
N
N
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D008862:Microsomes, Liver / Q000201:enzymology; D009538:Nicotine / Q000378:metabolism*; D010084:Oxidation-Reduction; D011817:Rabbits; D013237:Stereoisomerism
D009538:Nicotine; D003577:Cytochrome P-450 Enzyme System