Regio- and stereochemical studies on the .alpha.-carbon oxidation of (S)-nicotine by cytochrome P-450 model systems
- 1 March 1988
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 31 (3) , 637-640
- https://doi.org/10.1021/jm00398a024
Abstract
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 stereochemicl 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.This publication has 16 references indexed in Scilit:
- Steric course of hydroxylation at primary carbon atoms. Biosynthesis of 1-octanol from (1R)- and (1S)-[1-3H,2H,1H; 1-14C]octane by rat liver microsomesJournal of the American Chemical Society, 1982
- Stereochemistry and deuterium isotope effects in camphor hydroxylation by the cytochrome P450cam monooxygenase systemBiochemistry, 1982
- Changes in the metabolic profiles of R- and S-warfarin and R- and S-phenprocoumon as a probe to categorize the effect of inducing agents on microsomal hydroxylasesBiochemical Pharmacology, 1981
- Electron paramagnetic resonance study of the oxidation of N-methyl-substituted aromatic amines catalyzed by hemeproteinsBioorganic Chemistry, 1981
- N-Demethylation reactions catalyzed by chloroperoxidase.Journal of Biological Chemistry, 1980
- Optically pure (+)-nicotine from (.+-.)-nicotine and biological comparisons with (-)-nicotineJournal of Medicinal Chemistry, 1979
- Mechanism of N-demethylation of aminopyrine by hydrogen peroxide catalyzed by horseradish peroxidase, metmyoglobin, and protoheminBiochemistry, 1978
- Aliphatic hydroxylation by highly purified liver microsomal cytochrome P-450. Evidence for a carbon radical intermediateBiochemical and Biophysical Research Communications, 1978
- Intramolecular determination of primary kinetic isotope effects in hydroxylations catalyzed by cytochrome P-450Biochemical and Biophysical Research Communications, 1977
- Oxydation photochimique d'amines tertiaires et d'alcaloides—VITetrahedron, 1975