Nicotine l -oxide

The procedure given is essentially that described by Taylor and Crovetti.3 Nicotinamide-1-oxide (m.p. 275-276° dec.) has also been prepared by the alkaline hydrolysis of nicotinonitrile-1-oxide 4 and by the action of ammonium hydroxide on methyl nicotinate-l-oxide.6 The melting point of the product prepared by the latter synthesis is reported to be 282-284° dec. 

N-oxide reductase Removal of oxygen from N-oxides 4-Nitroquinolone-l-oxide, nicotine-N-oxide... 

FAD dependent oxidation of nucleophilic nitrogen, sulfur and phosphorus heteroatoms, e.g. conversion of nicotine to nicotine l -iV-oxide, cimetidine to cimetidine S-oxide... 

Park SB, Jacob P, 3rd, Benowitz NL, Cashman JR (1993) Stereoselective metabolism of (S)-(-)-nicotine in humans formation of trans-(S)-(-)-nicotine N-l -oxide. Chem Res Toxicol 6(6) 880-888... 

C. L. Crowley-Weber, K. Dvorakova, C. Crowley, H. Bernstein, C. Bernstein, H. Garewal and C. M. Payne, Nicotine increases oxidative stress, activates NF-kappaB and GRP78, induces apoptosis and sensitizes cells to genotoxic/xenobiotic stresses by a multiple stress inducer, deoxy-cholate relevance to colon carcinogenesis, Chem. Biol. Interact., 2003, 145(1), 53. 

Cashman, J.R. Park, S.B. Yang, Z.C. Wrighton, S.A. Jacob, P., Ill and Benowitz, N.L. Metabolism of nicotine by human liver microsomes Stereoselective formation of trans-nicotine-N -oxide. Chem Res Toxicol 5 639-646, 1992. 

Peterson, E.A. Trevor, A. and Castagnoli, N., Jr. Stereochemical studies on the cytochrome P-450 catalyzed oxidation of (S)-nicotine to the (S)-nicotine l (5 )-iminium species. JMed Chem 30 249-254, 1987. 

In 26 smokers, mean cotinine excretion was 1.39 mg/24 hr, while nicotine N-l -oxidc was excreted at a rate of 0.56 mg/24 hr in the same smokers (Jacob et al. 1986). The disposition of nicotine N-l -oxide in humans has been characterized (Park et al. 1993). Administration of deuterated nicotine N-T-oxide (figure 2) to humans results in the rapid excretion of the N-l -oxide largely unchanged in the urine. Examination of the stereochemistry of the nicotine N-l -oxide before and after administration showed that the stereochemistry of the excreted material was essentially identical to that of the administered compound. That no... 

Jacob, P., Ill Benowitz, N.L. Yu, L. and Shulgin, A.T. Determination of (S)-nicotine N-l oxide by gas chromatography following thermal conversion to 2-methyl-6-(3-pyridyl)-tetrahydro-l,2-oxazine. Analyt Chem 58 2218, 1986. 

It has been established independently and simultaneously in two laboratories that ornithine is the precursor of the pyrrolidine ring in nicotine (51, 52). Adult plants of N. rustica L. maintained 14 days in hydroponic solutions containing omithine-2-C are found to contain radioactive nicotine. After oxidation, carbon 2 of the pyrrolidine ring is isolated as nicotinic acid and carbons 3, 4, and 5 are isolated as barium carbonate. Nicotinic acid contains half the radioactivity and barium carbonate the other half. Decarboxylation of the nicotinic acid shows that the radioactivity is exclusively located in the carboxylic group. It is highly probable that the second half of the radioactivity is located on carbon 5, but the separation of this carbon from carbons 3 and 4 has not been effected (51, 52). 

The substituted pyridine derivatives are biologically active compounds. Nicotine, nomicotine and anabasine are natural insecticides known for a long time. Pyridine-2-thiol-l-oxide and pyridine-nitrile (2,6-dichloro-4-phenylpyridine-... 

The detoxification of nicotine in humans takes place mainly in the liver. The elimination half-life of the unaltered compound in blood plasma lies at around 2 hours, though its terminal excretion half-life in urine averages 11 hours. Nicotine is oxidised mainly (70-80 %) to cotinine, but also about 4 % to (l S,2 S)- and (Ti ,2 S)-nicotine ]SF-oxide. Cotinine, with an elimation half-life of up to 20 hours, is further hydroxylated in the 3 -position. Nicotine, cotinine and 3 -hydroxycoti-nine are excreted in the urine largely as glucuronic acid conjugates. [544]... 

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