Pyridine alkaloids, from tobacco

Cormor, W.M. and E.H. Hess The determination of cal-cinm in tobacco Tob. Sci. 5 (1961) 21-24. Constantinescu, T. A study of the influence of P-pyridine alkaloids from tobacco on the taste and aroma of tobacco Lucr. Cercet. Inst. Cercet. Proiect. Aliment. 10 (1972) 257-268. 

Paper chromatography was the first useful chromatographic method developed and used that gave satisfactory separations of pyridine alkaloids from tobacco (Jeffrey and Tso 1955 Jeffery and Eoff 1955). Paper chromatography is slow, laborious, and is not as sensitive as some of the more modern methods, but can still be used by breeders today when absolutely necessary. Either quantitative or qualitative determinations are possible with paper chromatography and both green and cured tobacco may be used. 

Thin-layer chromatography is frequently used to separate pyridine alkaloids from tobacco extracts. This method is frequently used by tobacco breeders to screen plant populations and individual tobacco plants to insure seed purity. Thin-layer is considerably faster than paper chromatography and can also be used as a preliminary cleanup for more sensitive methods for analytical analysis such as capillary gas chromatography (GC). Semi-... 

The Pyridine Famiiy. The tobacco alkaloids are the best representatives of this family. We have already viewed the structures of several of these alkaloids in Figure 3.1. They may have a pyrrrolidine ling as in nicotine or a piperidine ring as in anabasine attached to the 3-position of pyridine. They are biosynthesized from nicotinic add (Scheme 3.8). 

The pyridine system is found in natural products, for example, in nicotine (1) from tobacco, ricinine (2) fi-om castor bean, vitamins such as pyridoxine or vitamin Be (3) and vitamin P (4), and alkaloids such as coniine and piperine. Free pyridine is present in tobacco smoke. Diploclidine (5) and njdcinadine A (6) are two examples of recently isolated and structurally diverse natural products containing the pyridine core. ... 

Pyridine alkaloids are high boiling compounds which are stable to high temperatures. Nicotine, the most volatile of the pyridine alkaloids, is readily steam distilled from strong basic solutions however, secondary alkaloids are less volatile than nicotine and are not easily steam distilled quantitatively from basic aqueous solutions. Since nicotine is the predominant pyridine alkaloid present in most tobaccos, this analysis suffices for total alkaloids because secondary alkaloid concentrations are minimal. Tobacco alkaloids removed from basic aqueous solutions by steam distillation are quantified with a spectrophotometer. 

Nicotine is the main alkaloid of tobacco Nicotiana tabacum) of the Solana-ceae. Anabasine is the main alkaloid of Anabasis aphylla (Chenopodiaceae), although trace amounts are also present in tobacco. Both nicotine and anabasine possess strong insecticidal activity. The structures of these alkaloids also have similarities in that one contains a pyrrolidine ring derived from ornithine and the other a piperidine ring derived from lysine, both of which are joined at C-3 of the pyridine ring, itself derived from nicotinic acid [1]. These alkaloids were described in detail in Chapters 3 and 4 on ornithine-and lysine-derived alkaloids, respectively. The procedure for the formation of nicotine and anabasine by condensation of A -pyrrolidine and A -piperidine with a nicotinic acid moiety is shown in the figure [2]. 

Tobacco Alkaloids. The relatively small number of alkaloids derived from nicotinic acid (27) (the tobacco alkaloids) are obtained from plants of significant commercial value and have been extensively studied. They are distinguished from the bases derived from ornithine (23) and, in particular, lysine (24), since the six-membered aromatic substituted pyridine nucleus common to these bases apparendy is not derived from (24). 

Myosmine (3[2-pyrrolidinyl]pyridine) and nicotine (3[l-methyl-2-pyrrolidinyl]pyridine) (Section 1, Appendix) and a number of related bioactive alkaloids occur in Nkotiana tabacum (tobacco) (Solanaceae) and variously in other Solanaceae such as Duboisia species. Nicotine and the related tobacco compounds nicotyrine and (—)-nornicotine are agonists (neurotransmitter mimics ) of the so-called (nicotine binding) nACh-R involved in neurotransmission and in neuromuscular transmission for skeletal muscle. The extraordinary addictiveness of nicotine derives from nACh-R agonists causing dopamine release and activating the mesolimbic dopamine system yielding reward effects. The antidepressant (—)-cotinine is the major nicotine metabolite in humans and a nicotinic agonist. 

Balasubrahmanyam and Quin (175) identified quinoline, isoquinoline, and various substituted pyridines in the pyrolysates from the tobacco alkaloids nornicotine and myosmine. 

The IR-spectra of 41 tobacco alkaloids and related compounds have been tabulated (S5). Nornicotine, nicotine, myosmine, nicotyrine, anabasine, anatabine, and dihydronicotyrine were separated from an extract of tobacco alkaloids by countercurrent partition (86). Thin-layer chromatography has been used to separate nicotine, nornicotine, anabasine, and nicotyrine (57). The use of gas chromatography to separate tobacco alkaloids has been studied. The retention times of 11 tobacco alkaloids on polyethylene glycol columns has been reported (88) and the effect of the column packing on the retention times of pyridine bases has been described (89). Mixtures containing pyrrolidine, piperidine, pyridine, and various alkylated pyridines have been separated using programed temperature control (90). 

Interest in alkaloids of the nicotine group appears to be on the increase. A review has appeared covering tobacco-specific nitrosamines, which may be causative factors in tobacco-related cancers. The solution conformation, and proton, deuterium, carbon-13, and nitrogen-15 n.m.r. spectra of nicotine and its 2- and 4-isomers, have been studied. A new synthesis of nornicotine and nicotine has been described, and a quantitative carbon-13 n.m.r. spectral analysis of nicotine that is labelled at positions 1, 2, and 3 with carbon-13 been presented. The synthesis and mass spectrometry of several structurally related nicotinoids have been reported. Nicotine is dehydrogenated on irradiation in benzene solution in the presence of benzophenone to l -methyl-2 -(3-pyri-dyl)pyrrole. ° Nornicotine has been synthesized in four steps from 3-bromo-pyridine and N-3-butenyl-phthalimide, using a palladium-catalysed vinylic... 

Physiology biosynthesis Like the tropane alkaloids, T. a. are formed in the roots and transported to the aboveground parts for storage by the plant s phloem system. In some sorts of tobacco plants a part of the nicotine is demethylated to nomicotine during transport to the shoot. Nomicotine and anabasine are often the main alkaloids in the so-called nicotine-poor tobacco plant types. The T. a. are formed biogenetically from nicotinic acid, made available via the pyridine nucleotide cycle (see nicotinamide), and a pyrrolidine or piperidine building block (figure). In the case of nicotine, like for the tropane alkaloids, Al-methylpyr-roline is an intermediate, in the biosynthesis of anabasine the intermediate is a piperidine derived from the amino acid lysine (see piperidine alkaloids). 

Nicotinic acid (Figure 2.9) provides alkaloids with the pyridine nucleus in the synthesizing process. This nucleus appears in such alkaloids as anaba-sine, anatabine, nicotine, nornicotine, ricine, and arecoline. Moreover, many alkaloids contain the pyridine nucleus as part of their total skeleton. For example, anabasine is derived from nicotinic acid and lysine.Alkaloids with the pyridine nucleus occur in such plants as tobacco (Nicotiana... 

Tobacco is derived from the leaves of Nicotiana tabacum (Solanaceae), and it was used to treat headache and toothache. However, it is not used as a medicine now, and smoking tobacco is now a global addictive habit. Tobacco leaf contains a large amount of nicotine (2-8%), and the nicotine extracted as nicotine sulfate is used as an insecticide in agriculture. Tobacco leaf contains more than ten related alkaloids other than nicotine, and all of these alkaloids possess a pyridine skeleton with 3-substitution. The main alkaloids other than nicotine, anabasine and nor-nicotine, are isolated from the leaf material, and these alkaloids also possess insecticidal activity. 

Alkylated pyridines play an important role in chemical technology as well as in nature. Nicotine is a natural alkylpyridine derivative, found in the tobacco plant this alkaloid was used from the 17 th century until the 1950 s as a plant protection agent. 

The main alkaloid found in tobacco plants, nicotine, is composed of a pyrrolidine ring and a pyridine ring (Fig. 5). The pyrrolidine moiety is derived from Y-methylputrescine, which is formed from putrescine by putrescine N-methyltransferase (PMT) (Katoh et al., 2005). The pyridine moiety of nicotine is derived Irom nicotinic acid. Nicotine is exclusively synthesized in the roots and is translocated to the leaves via the xylem. Multiple structural genes... 

The main alkaloid of different cultivars of commercial tobacco species Nicotiana tabacum and N. rustica, Solanaceae) is nicotine, (S)-l-methyl-2-(pyrid-3-yl)pyrrolidone or (S)-3-(l-methylpyrrolidin-2-yl)pyridine, 10-7. Nicotine is also present in small quantities in other plants (about 24 species of 12 plant families), but especially in plants of the nightshade family, which also includes potatoes, tomatoes and eggplants (aubergines). Biosynthesis of nicotine takes place in the roots of plants, from where nicotine is transported to the aerial parts, especially to the leaves. 

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