Chemistry:Nornicotine

From HandWiki

Nornicotine is an alkaloid with the formula NC
5H
4–C
4H
7NH. A colorless oil, it is a significant alkaloid in Nicotiana, the tobacco plant, although less abundant than nicotine.[1] It is structurally similar to nicotine but does not contain a methyl group.

Biochemical processes

In nature, nornicotine is produced by demethylation of nicotine. This process, which requires oxygen, is catalyzed by nicotine N-demethylase, a cytochrome P450.[1]

nornicotine is a precursor to the carcinogen N-nitrosonornicotine that is produced during the curing and processing of tobacco.[2] Nornicotine can react in human saliva to form N-nitrosonornicotine,[3] a known type 1 carcinogen.[4]

Synthesis

There are several routes for the synthesis of nornicotine. One route is the demethylation of nicotine, which can be accomplished by reaction with silver oxide.[5]

150px→H2OAg2O 170px

Another route is the partial reduction of 3-myosmine, which can be accomplished by standard catalytic hydrogenation conditions using palladium as a catalyst[6] or with sodium borohydride.[7] This reaction gives the racemic product.

150px→H2Pd/C 170px

Nornicotine was first synthesized from nicotine-N-oxide.[8]

Pharmacology

Nornicotine possess high affinity for alpha-6 and alpha-7 subunits of nAChRs.[9] It also inhibits DAT in striatum via nAChR and releases dopamine in rats.[10][11][12]

References

  1. ↑ 1.0 1.1 Dewey, Ralph E.; Xie, Jiahua (2013). "Molecular genetics of alkaloid biosynthesis in Nicotiana tabacum". Phytochemistry 94: 10–27. doi:10.1016/j.phytochem.2013.06.002. PMID 23953973. 
  2. ↑ Siminszky, B. (2005). "Conversion of nicotine to nornicotine in Nicotiana tabacum is mediated by CYP82E4, a cytochrome P450 monooxygenase". Proceedings of the National Academy of Sciences 102 (41): 14919–24. doi:10.1073/pnas.0506581102. PMID 16192354. Bibcode: 2005PNAS..10214919S. 
  3. ↑ "Nornicotine nitrosation in saliva and its relation to endogenous synthesis of N'-nitrosonornicotine in humans". Nicotine & Tobacco Research 15 (2): 591–5. February 2013. doi:10.1093/ntr/nts172. PMID 22923602. 
  4. ↑ "List of Classifications – IARC Monographs on the Identification of Carcinogenic Hazards to Humans". https://monographs.iarc.fr/list-of-classifications. 
  5. ↑ Spaeth (1936). "Über dasd-Nor-nicotin". Chem. Ber. 69 (2): 250–251. doi:10.1002/cber.19360690207. 
  6. ↑ Haines (1945). "Chemical Reactivity of Myosmine". J. Am. Chem. Soc. 67 (8): 1258–1260. doi:10.1021/ja01224a011. Bibcode: 1945JAChS..67.1258H. 
  7. ↑ Dickerson, TJ; Janda, KD (2002). "Aqueous aldol catalysis by a nicotine metabolite". J. Am. Chem. Soc. 124 (13): 3220–1. doi:10.1021/ja017774f. PMID 11916401. Bibcode: 2002JAChS.124.3220D. .
  8. ↑ Max Polonovski; Michel Polonovski (1927). "β-Pyridyl-α-pyrrolidine (nornicotine)". Comptes Rendu 184: 1333-5. 
  9. ↑ "The pharmacological activity of icotine and nornicotine on nAChRs subtypes: relevance to nicotine dependence and drug discovery". Journal of Neurochemistry 101 (1): 160–7. April 2007. doi:10.1111/j.1471-4159.2006.04355.x. PMID 17241116. 
  10. ↑ "Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation". Synapse 61 (3): 157–65. March 2007. doi:10.1002/syn.20351. PMID 17146768. 
  11. ↑ "Nornicotine, a nicotine metabolite and tobacco alkaloid: desensitization of nicotinic receptor-stimulated dopamine release from rat striatum". European Journal of Pharmacology 428 (1): 69–79. September 2001. doi:10.1016/s0014-2999(01)01283-3. PMID 11779039. 
  12. ↑ "S(-)-nornicotine increases dopamine release in a calcium-dependent manner from superfused rat striatal slices". Journal of Neurochemistry 60 (6): 2167–74. June 1993. doi:10.1111/j.1471-4159.1993.tb03502.x. PMID 8492124. 



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