Nomicotine Nornicotine

A mixture of A -hydroxyacylnornicotines (4), including lV -(3-hydroxy- 12-methyl-tridecanoyl)nomicotine as the major component, was extracted from leaves of Nicotiana repanda, N. stocktonii and N. nesophila [63]. The mixture was toxic to larvae of the tobacco homworm, Manduca sexta [63]. Feeding experiments with [2-14C]-nicotine and [2-l cj-nornicotine suggested that the hydroxyacylnomicotines were biosynthesized in trichomes and then rapidly secreted from the plant [64], The hydroxyacylnomicotines inhibited the growth of wheat coleoptiles and displayed antibiotic activity [65]. 

At the Austria Tabakwerke A.G., Klus and Kuhn (2136) detected 40 ng/cig of NNN in the MSS from cigarettes made with nomicotine-rich tobacco (1.95% nornicotine). However, they failed to detect NNN in the MSS from a blended commercial cigarette. They concluded ... 

As in the case of nicotine and nicotyrine, several structural isomers of nornicotine have been synthesized. 2, 2-Nomicotine is obtained as an intermediate in the synthesis of 2, 2-nicotine (383). 

Miyano M, Matsushita H, Yasumatsu N, Nishida K (1979) New minor alkaloids in burley tobacco (Nicotiana tabacum) Agric Biol Chem 43 1607-1608 Miyano M, Yasumatsu N, Matsushita H, Nishida K (1981) l -(6-Hydroxyoctanoyl)nomicotine and l -(7-hydroxyoctanoyl)nornicotine, two new alkaloids from Japanese domestic tobacco. Agric Biol Chem 45 1029-1032... 

The results (Leete and Chedekel, 1974) indicate that 48% of [2- H](-)-nomicotine and 52% [2- C](+)-nomicotine is incorporated from the labeled nicotine. Thus if (+)-nornicotine is formed from (-)-nicotine, the transformation must involve the loss of the hydrogen from C-2 however, almost the same [ HA C]ratio occurs as in the administered mixture of [2 - H](-)-nicotine and [2 2- C](+)-nicotine, which indicates that in N. glauca (+)- and (-)-nicotine are demethylated at similar rates. If the demethylation had been stereospeciflc for (-)-nicotine, the resultant nomi-cotine would have its [ HA C]ratio doubled. This led the authors to propose a scheme for the formation of (+)-nicotine and (-)-nicotine (Figure 6.11). This mechanism accounts for the partial racemization of the nornicotine derived from (-)-nicotine a Cope elimination of nicotine N -oxide (a) would involve one of the hydrogens at C-3, which would provide the unsaturated compound (b). Elimination of water from this hydroxy amine yields the Schiff base (c), which upon hydrolysis yields formaldehyde or other Cl metabolite and the primary amine (d). Cyclization of this intermediate yields (+)- and ( )-nomicotine. Leete and Chedekel presume that these steps are enzyme mediated, and it is to be expected that the final cyclization would yield a preferential amount of (+)- or (-)-nornicotine however, the mechanism which yields (+)-nornicotine from (-)-nicotine remains unknown. 

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