Minor alkaloids anatabine

Precursors and Formation. Tobaccos used for commercial products in the U.S.A, contain between 0,5 and 2,7% alkaloids. Nicotine constitutes 85-95% of the total alkaloids (14,26,27). Important minor alkaloids are nornicotine, anatabine, anabasine, cotinine and N -formylnornicotine (Figure 6), Several of these alkaloids are secondary and tertiary amines and, as such, amenable to N-nitrosation. The N-nitrosated alkaloids identified to date in tobacco and tobacco smoke include N -nitrosonornico-tine (NNN), 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) and N -nitrosoanatabine (NAT Figure 7). In model experiments, nitrosation of nicotine also yielded 4-(methylnitrosamino)-4-(3-pyridyl)butanal (NNA 28). 

The primary alkaloid in tobacco is nicotine, but tobacco also contains small amounts of minor alkaloids such as anabasine, anatabine, myosmine, and others. The minor alkaloids are absorbed systemically and can be measured in the urine of smokers and users of smokeless tobacco (Jacob et al. 1999). The measurement of minor alkaloids is a way to quantitate tobacco use when a person is also taking in pure nicotine from a nicotine medication or a nontobacco nicotine delivery system. This method has been used to assess tobacco abstinence in clinical trials of smoking cessation with treatment by nicotine medications (Jacob et al. 2002). 

Tobacco use is primarily due to psychopharmacological effects of nicotine (Henningfleld et al. 2006). Nicotine is a tobacco alkaloid, a basic substance that contains a cychc nitrogenous nucleus. In Nicotiana plants, most alkaloids are 3-pyridyl derivatives In cured leaf of Maryland Robinson Medium Broadleaf, 24 pyridine derivatives were identified, including nicotine, nomicotine, anabasine, oxynicotine, myosmine, 3-acetylpyridine, 2,3 -dipyridyl, iticotinamide, anatabine, nicotinic acid, and unidentified pyridine alkaloids of derivatives thereof (Tso 1990). Nicotine is the principal alkaloid in commercial tobacco (this was confirmed in 34 out of 65 Nicotiana species) nomicotine, rather than nicotine, appears to be the main alkaloid in 19 out of 65 species and anabasine is the third most important. In addition to the above-mentioned principal and minor alkaloids, the presence of many trace amounts of new alkaloids or their derivatives were frequently reported, including, for example, 2.4 -dipyridyl, 4,4 -dipyridyl, N -formylanabasine, A -formylanatabine, N -acetylanatabine, N -hexanoyl-nomicotine, N -octanoyl-nomicotine, T-(6-hydroxyoctanoyl) nomicotine, and l -(7-hydroxyoctanoyl) nor-nicotine. 

Anatabine (177) and A -methylanatabine are minor alkaloids of tobacco.1 5-167 Racemic 177 was synthesized by the BF3-catalyzed condensation (cf. Section II, A) of diethyl 3-pyridylmethylenebis-carbamate (176) with 1,3-butadiene and subsequent removal of the JV-ethoxycarbonyl group.168,169... 

Bush determined the four most important tobacco alkaloids (nicotine, nornicotine, anabasine and anatabine) using a 10 % DC 550 packed column on Chromosorb 60-80, and using isoquinoline as an internal standard. The alkaloids were extracted with benzene-chloroform (9 1) after treatment of the tobacco sample (1 g) with bariumhydroxide and water. The organic phase was concentrated and used for the gas chromatographic determination. Because of the great differences in the amounts of the minor alkaloids and nicotine in most tobacco samples, two extractions, each with an appropriate amount of internal standard, were required for a complete assay. The precision of the quantitative analysis on tobacco samples of different alkaloids is given in Table 5.6. 

Over sixty species of Nicotiana exist that produce nicotine alkaloids (nicotine, nornicotine, anatabine, anabasine). Nicotine is the predominant alkaloid in over 50% of the Nicotiana species. Nornicotine is the major alkaloid in about 30% to 40% of Nicotiana species. Anabasine and anatabine are not usually the principal alkaloids in Nicotiana (17B05). Tobaccos that accumulate and have high levels of alkaloids tend to also have accumulations of minor alkaloids, for example, cotinine, myosmine, nicotyrine, 2,3 -bipyridine, and numerous derivatives of the major alkaloids, for example, alkyl, acyl, and nitroso derivatives of nicotine and the other... 

Although nicotine is the principal alkaloid in commercial tobaccos (Nicotiana tabacum and Nicotiana rusticd), norni-cotine is the main alkaloid in most other species of Nicotiana. Anabasine is the third most abundant tobacco alkaloid. Anabasine is found in the stem of the Nicotiana glauca plant. Anatabine has been reported as a minor alkaloid in the roots of these plants, although it is present also in the leaf and stem... 

Anatabine is the most abundant of the minor alkaloids of tobacco. It has been established that both rings of this alkaloid are derived from the dimerization of nicotinic acid (Figure 6.9) [36, 37]. 

N. hesperis). Ontogenetic variation of the alkaloid profile was observed for N. glauca (Lovkova et al. 1976). Nicotine was the main nicotinoid in 15-day-old seedlings whereas anabasine prevailed in 48-day-old plants. Anatabine turned out to be always a minor component with the exception of N. otophora where it represented the principal alkaloid in the leaves (roots nicotine). 

Nicotine in tobacco is always accompanied by three other prominent alkaloids nomicotine, (S)-2-(3-pyridyl)pyrrolidone, anatabine, (S)-2-(pyrid-3-yl)-l,2,5,6-tertrahydropyridine and anabasine, (S)-2-(pyrid-3-yl)piperidine (10-7). Apart from these main alkaloids, more than 20 other minor tobacco alkaloids (10-8) have been identihed. 

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