Alkaloids nicotinic acid

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). 

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. ... 

Nicotine adenine dinucleotide phosphate (NADP+), 24 147 Nicotinic acid, 9 477-478 26 291 alkaloid precursor, 2 78 Ni-Cr alloys, 23 499. See also Nickel-chromium entries NiCrAlY coatings, 13 508 nido designation boranes, 4 184-186 boron hydrides, 4 170, 172-176 Nidrel, molecular formula and structure, 5 129t... 

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. 

Nicotine Nicotine, l-methyl-2-(3-piridyl)pirrolidine (13.1.27), is an alkaloid that is isolated from the plant Nicotiana (Nicotiana tabacum, Nicotiam rustica, and others) and can be synthesized in varions ways [33-36]. In particular, it is proposed to proceed from nicotinic acid ethyl ester, which is condensed with iV-methylpyrrolidone, giving l-methyl-2-nicotinoyl pyrrolidone-2 (13.1.23). Acidic hydrolysis of this compound leads to an opening of the pyrrolidine ring giving the intermediate (13.1.24), which under the reaction conditions is decarboxylated to the /-aminoketone (13.1.25). The carbonyl group is reduced to an alcohol and the resnlting prodnct (13.1.26) undergoes dehydration to nicotine (13.1.27). 

Nicotinic acid Nicotinic acid-derived alkaloids True alkaloids Pyridine alkaloids Sesquiterpene pyridine alkaloids... 

Nicotinic acid (Figure 29) provides alkaloids with the pyridine nucleus in the synthesizing process. This nucleus appears in such alkaloids as anabasine, anatabine, nicotine, nornicotine, ricine and arecoline. Moreover, many alkaloids... 

Figure 29. The nucleus of alkaloids derived from nicotinic acid.

Alkaloids derived from nicotinic acid contain a pyridine nucleus. Nicotinic acid itself is synthesized from L-tryptophan via A-formylkynurenine, L-kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid. 

The other alkaloids derived from nicotinic acid, with pyridine nucleus such as arecoline, arecaidine and guvacoline, are tetrahydronicotinic acid (guvacine) derivatives. 

Pyridine alkaloids are compounds with a pyridine nucleus and a pyrrohdine or piperidine unit. The pyrrohdine ring appears in nicotine and the piperidine ring in anahasine. Typical alkaloids from this group are nomicotine and anatahine. The a of pyridine alkaloids is nicotinic acid, the j8 is dihydronicohnic acid, the q> is 1,2-dihydropyridine (Figure 61). The A is nicotine and its P is nomicotine. ... 

Natural sesquiterpene pyridine alkaloid formation needs two precursors, one for the pyridinium moiety and another for the sesquiterpene moiety. The a for formation of the pyridinium moiety is nicotinic acid, which reacts with isoleucine and, by oxidative reaction, produces evoninic acid, wilfordic acid or edulinic acids, a for the sesquiterpene moiety is still open to question, but E, E-famesyl cation has been suggested as one possibility and hedycarylol as a second. This moiety is dihydroagarofuran. Therefore, a for the sesquiterpene pyridine alkaloids is nicotinic acid and E, E-famesyl cation and, controversially, hedycaryol. The /3 is amacrocycling ring formation substance (two moieties), from which the alkaloid forms (Figure 62). 

NT437 Leete, E., and S. A. Slattery. Incorporation of (2- C) nicotinic acid into the tobacco alkaloids. Biosynthesis of anatabine and alpha, beta-dipyridyl. J Am Chem Soc 1976 98 6326. 

The alkaloids are also relevant to drug design. Alkaloids are complex heterocyclic compounds that contain nitrogen and thus have base-like (hence the term alkaloid ) properties they are extremely structurally diverse. Nicotine is one of the simplest alkaloids. Oxidation of nicotine produces nicotinic acid, a vitamin that is incorporated into the important coenzyme nicotinamide adenine dinucleotide, commonly referred to as NAD" (oxidized form). The neurotransmitter serotonin is an alkaloid containing the aromatic indole ring system. 

Labeling by deuterium or carbon-13 always leads to unequivocal signal identification of specific carbon atoms [600, 602, 640], After the administration of [5,6-14C-13C2]nicotinic acid to Nicotiana tabacum and N. glauca labeled anabasine anatabine, nicotine and nomicotine could be isolated. The satellites at the resonances of the labeled natural products helped to complete the signal assignments of the 13C NMR spectra of these alkaloids [602]. 

The tobacco alkaloids, especially nicotine, are derived from nicotinic acid (see page 311) but also contain a pyrrolidine ring system derived from ornithine as a portion of their structure. 

This allows an aldol-type reaction with the A-methylpyrrolinium cation, and finally dehydrogenation of the dihydropyridine ring back to a pyridine gives nicotine. Nornicotine is derived by oxidative demethylation of nicotine. Anaba-sine is produced from nicotinic acid and lysine via the A1 -piperidinium cation in an essentially analogous manner (Figure 6.32). A subtle anomaly has been exposed in that a further Nicotiana alkaloid anatabine appears to be derived by... 

Nicotinic acid undoubtedly provides the basic skeleton for some other alkaloids. Ricinine (Figure 6.35) is a 2-pyridone structure and contains a nitrile grouping, probably formed by dehydration of a nicotinamide derivative. This alkaloid is a toxic constituent of castor oil seeds (Ricinus communis Euphorbiaceae), though the toxicity of the seeds results mainly from the polypeptide ricin (see page 434). Arecoline (Figure 6.36) is found in Betel nuts (Areca catechu Palmae/Arecaceae) and is a tetrahydronicotinic acid derivative. Betel nuts are chewed in India and Asia for the stimulant effect of arecoline. 

Alkaloids of the Celastraceae.—The structures of eleven new alkaloids of this family, all related to nicotinic acid, have been elucidated, largely by interconversions and degradations and by spectral study and analysis.28-30... 

The structure of onychine, an alkaloid of Onychopetalum amazonicum that has hitherto been formulated as (33), must be revised to (34). Both structures have been synthesized the former was found to be different from onychine and the latter identical with it.33 Three stereospecific syntheses of sesbanine (35) have been reported. In one, 4-(methoxycarbonyl)nicotinic acid is the starting point (Scheme 3).34 The other two both start from 4-methylnicotinonitrile, one35 leading to ( )-sesbanine and the other to the (+)-enantiomer.35 10-Deoxyses-banine has also been synthesized, by a route which appears applicable to the alkaloid itself.37... 

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