Tobacco alkaloids anabasine

The tobacco alkaloid anabasine (37) has been synthesized from 3-pyridyl-lithium (prepared from 3-bromopyridine and t-butyl-lithium) by reaction with A piperideine at —120 °C.46... 

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... 

In the tobacco alkaloids anabasine (26) and anatabine (27), a lysine derivative is condensed with a derivative of nicotinic acid to yield a system reminiscent of nicotine (Fig. 29.9) (Leete, 1977, 1983a). 

Tobacco and its alkaloids have long ceased to have any therapeutic importance, but their extensive use as insecticides and the demand for nicotine for the manufacture of nicotinic acid have stimulated interest in processes of extraction and methods of estimation. On the latter subject there is a voluminous literature, of which critical resumes have been published by various authors.Recent work on this subject has been specially concerned with (1) the development of miero- and semi-miero-methods suitable for estimating nieotine in tobacco smoke and the distribution of nieotine on sprayed garden produce, in treated soils and in tobaeeo leaves,(2) the study of conditions necessary to ensure satisfactory results in using particular processes, " and (3) methods of separation and estimation of nicotine, nomicotine and anabasine in mixtures of these bases. ) In the United States and in Russia considerable interest is being shown in the cultivation of types of tobacco rich in nicotine, in finding new industrial uses for tobacco and its alkaloids, and in possible by-products from tobacco plants such as citric and malic acids, i " Surveys of information on tobacco alkaloids have been published by Jackson, i Marion and Spath and Kuffner. ... 

The primary psychoactive alkaloid in tobacco is nicotine (figure 4.9), occuring between 0.6 and 9.0% (Robbers et al. 1996 Gruenwald et al. 1998). Other alkaloids include nornicotine, N-formylnornicotine, cotinine, myosmin, )S-nicotyrine, anabasine, and nicotellin. Nicotine alone can produce the effects commonly associated with tobacco use, but other tobacco alkaloids are likely to contribute. 

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. 

Secondary alicyclic amines, such as pyrrolidine and piperidine, have many properties typical of the corresponding aliphatic amines. Metabolic oxidation at secondary alicyclic nitrogens results in the formation of hydroxylamines, which may then undergo enzymic or non-enzymic conversion to nitrones, and in some cases to nitroxide radicals. For example, the 2-substituted piperidino derivative (- )-anabasine (1), a tobacco alkaloid, is metabolized initially to a hydroxylamine (2) and then to the nitrone (3), when incubated with liver and... 

Heterocyclic secondary amines, such as phenmetrazine or (—)-anabasine, a minor tobacco alkaloid, undergo metabolic attack at the amino groups to finally yield nitrones 37 and 38, respectively, when incubated with tissue preparations from various mammals90,91. 

The well-known piperidine alkaloid anabasine, found in Anabasis aphylla L. (Chenopodiaceae) and Nicotiana glauca Graeb. (Solanaceae), is thought to be synthesized in plants through dimerization of A1-piperideine (followed by oxidation).243 A terpyridine nicotelline (173) was found in tobacco leaf,244andits structure was proved by synthesis.245... 

Anabasine, a minor tobacco alkaloid in plants of Anabasis aphylla, is found in trace amounts in tobacco smoke, and, like nicotine, is one of the earliest known insecticides. In maximum current generation studies anabasine is equivalent to ACh and appears to act at the a nicotinic ACh receptor. ISQ analogs of anabasine were prepared but no pharmacological activity was reported [33],... 

Harke and Drews used a 50 m long stainless steel capillary column, 0.5 mm I.D., coated with Ucon LB 550 X (polyethylene glycol) and K0H for the separation of tobacco alkaloids. A typical chromatogram of a test-mixture containing 3-pyridyl-n-propylketon, nicotine, nor-nicotine, myosmine, anabasine and nicotyrine is shown in Figure 5.1 (Tobacco alkaloids). 

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. 

The minor airborne tobacco alkaloids, nornicotine, myosmine and anabasine, did not interfere with nicotine. The standard curve was linear over a range of 10-500 yg/ml with a relative standard deviation of 95 % for 10-50 yg/ml. 

Actinidine (92), a plant alkaloid (see section 8), is also a minor component of the defence secretion of the Australian cock-tail ant Iridomyrmex nitidceps (G.W.K. Cavill et al.. Tetrahedron, 1982, 38, 1931), a fact which indicates that ants may obtain toxins (or at least their precursors) from dietary sources. Actinidine has been synthesised (M. Nitta, A. Sekiguchi and H. Koba, Chem.Letters, 1981, 933). Anabaseine (118), a dihydro derivative of anabasine a well known tobacco alkaloid, is present in the poison glands of Aphaenogaster ants for which it also an attractant (J.W. Wheeler et al.. Science, 1981, 211, 1051). Ants from Puerto Rico produce the simple tetrahydropyridine (119) (T.H. Jones, M.S. Blum and... 

The most important natural sources of minor tobacco alkaloids are from Nicotiana species, and at least eight minor tobacco alkaloids are shown in Figure 1. Since the chemical structures and physical properties of these minor tobacco alkaloids are similar to that of nicotine, some of them are shown to exhibit similar pharmacological activities as those of nicotine, although with a much lower potency. Table 2 shows their relative molar potency in some pharmacological systems. When nornicotine or anabasine was applied to the cat cervical ganglion, initial stimulation was followed by paralysis. On the autonomic ganglion and neuromuscular junction, nornicotine is only one-fifth to one-tenth as active as nicotine. Both nornicotine and anabasine have vaso-depressor action and affect the respiratory system. 

Dubinin and Chelintsev (1075a) reported quinoline, isoquinoline, and several substituted pyridines in a pyrolysate of anabasine, a tobacco alkaloid structurally related to nicotine. 

Spath, E. and E. Kesztler Uber neue Tabakalkaloide. XII. Uber das Vorkommen von tobacco alkaloids. XII. On the occurrence of [Pg.1459]

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). 

Among the tobacco alkaloids, nicotine and anabasine are the major components. All tobacco alkaloids are toxic. The toxicity of nicotine and anabasine is discussed below under separate headings. There are also other harmful substances that are not alkaloids. These include nitrosamines, neophytadiene, solanesol, polyphenols, hydrocarbons, and steroids. 

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 use of HPLC for separation of tobacco alkaloids has been limited to few studies (Court 1986). Saunders and Blume (1981) developed a procedure for analyses of nicotine, nornicotine, anabasine, and anatabine in tobacco. This method utilized a pBondapak Cig reversed-phase column. The mobile phase of 40% methanol containing 0.2% phosphoric acid was adjusted to pH 7.25 with triethylamine. Retention times with 0.5ml/min flow rates were 23 min for nicotine, 13.9min for anatabine, 12.2min for anabasine, and ll.Omin for nornicotine. This method is capable of analyzing samples containing 40-50 ng of alkaloid, and quantitative results were reliable. The column was stable for 800-1000 injections before it showed appreciable degradation in separation but was still capable of separating nicotine and nornicotine. 

Also obtained from tobacco are the alkaloids (-)-anabasine and (-)-anatabine and related derivatives. (-)-Anabasine is biosynthesized by combining nicotinic acid and a piperidine ring derived from lysine. 

The structure information has been obtained with the aid of vicinal proton-proton couplings by Saloranta and Leino " for two synthetically obtained tobacco alkaloids ( )-anatabine, i.e. l,2,3,6-tetrahydro-2,3 -bipyridine, and ( )-anabasine, i.e. l,2,3,4,5,6-hexahydro-2,3 -bipyridine by Regalado et alP for seven acanthifoliosides, novel steroidal saponins... 

A series of 10 tobacco alkaloids (e.g., (/, 5)-anatabine, (S)-(—)-cotinine, -nicotyrine, -nicotine, and -anabasine, and syn-nicotine- -oxide) were separated on... 

Meanwhile, in 2008, Charette and coworkers [129] demonstrated a direct C-H arylation of pyridine N-oxide surrogates such as N-iminopyridinium yhde 91 with aryl hahdes. They also apphed their methodology to the synthesis of anabasine, a well-known tobacco alkaloid (Scheme 17.25). 

Fig. 3.10 Biosynthesis of the major tobacco alkaloids nicotine, anabasine, and anatabine...

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