Nornicotine

Nornicotine
Names
IUPAC name
3-[(2S)-2-Pyrrolidinyl]pyridine
Other names
Demethylnicotine
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.165.066
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).
Infobox references

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.[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]

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.

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. ^ a b 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. 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 Rendu. 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.
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