Nornicotine

Nornicotine
Names
IUPAC name
3-[(2S)-2-Pyrrolidinyl]pyridine
Other names
Demethylnicotine
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.165.066 Edit this at Wikidata
UNII
  • InChI=1S/C9H12N2/c1-3-8(7-10-5-1)9-4-2-6-11-9/h1,3,5,7,9,11H,2,4,6H2/t9-/m0/s1
    Key: MYKUKUCHPMASKF-VIFPVBQESA-N
  • InChI=1/C9H12N2/c1-3-8(7-10-5-1)9-4-2-6-11-9/h1,3,5,7,9,11H,2,4,6H2/t9-/m0/s1
    Key: MYKUKUCHPMASKF-VIFPVBQEBM
  • n1cccc(c1)[C@H]2NCCC2
Properties
C9H12N2
Molar mass 148.209 g·mol−1
Appearance colorless oil
Density 1.044 g/cm3
Boiling point 111 °C (232 °F; 384 K) 3 mm Hg
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Nornicotine is an alkaloid with the formula NC5H4−C4H7NH. A colorless oil, it is a significant alkaloid in Nicotiana, the tobacco plant, although less abundant than nicotine. 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.

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

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.

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

Nornicotine was first synthesized from nicotine-N-oxide.

Pharmacology

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

References

  1. 1 2 Dewey, Ralph E.; Xie, Jiahua (2013). "Molecular genetics of alkaloid biosynthesis in Nicotiana tabacum". Phytochemistry. 94: 10–27. Bibcode:2013PChem..94...10D. 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. Bibcode:2005PNAS..10214919S. doi:10.1073/pnas.0506581102. PMC 1253577. PMID 16192354.
  3. ↑ Knezevich A, Muzic J, Hatsukami DK, Hecht SS, Stepanov I (February 2013). "Nornicotine nitrosation in saliva and its relation to endogenous synthesis of N'-nitrosonornicotine in humans". Nicotine & Tobacco Research. 15 (2): 591–5. doi:10.1093/ntr/nts172. PMC 3611998. PMID 22923602.
  4. ↑ "List of Classifications – IARC Monographs on the Identification of Carcinogenic Hazards to Humans". monographs.iarc.fr. Retrieved 2020-07-22.
  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. Bibcode:1945JAChS..67.1258H. doi:10.1021/ja01224a011.
  7. ↑ Dickerson, TJ; Janda, KD (2002). "Aqueous aldol catalysis by a nicotine metabolite". J. Am. Chem. Soc. 124 (13): 3220–1. Bibcode:2002JAChS.124.3220D. doi:10.1021/ja017774f. PMID 11916401..
  8. ↑ Max Polonovski; Michel Polonovski (1927). "β-Pyridyl-α-pyrrolidine (nornicotine)". Comptes Rendus. 184: 1333-5.
  9. ↑ Papke RL, Dwoskin LP, Crooks PA (April 2007). "The pharmacological activity of icotine and nornicotine on nAChRs subtypes: relevance to nicotine dependence and drug discovery". Journal of Neurochemistry. 101 (1): 160–7. doi:10.1111/j.1471-4159.2006.04355.x. PMID 17241116.
  10. ↑ Middleton LS, Crooks PA, Wedlund PJ, Cass WA, Dwoskin LP (March 2007). "Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation". Synapse. 61 (3): 157–65. doi:10.1002/syn.20351. PMID 17146768. S2CID 35071082.
  11. ↑ Dwoskin LP, Teng LH, Crooks PA (September 2001). "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. doi:10.1016/s0014-2999(01)01283-3. PMID 11779039.
  12. ↑ Dwoskin LP, Buxton ST, Jewell AL, Crooks PA (June 1993). "S(-)-nornicotine increases dopamine release in a calcium-dependent manner from superfused rat striatal slices". Journal of Neurochemistry. 60 (6): 2167–74. doi:10.1111/j.1471-4159.1993.tb03502.x. PMID 8492124. S2CID 25622404.