Tobacco piperidine alkaloid

Felpin, F.X., Girard, S., Vo-Thanh, G., Robins, R.f, ViUieras, L, Lebreton, L (2001) Efficient Enantiomeric Synthesis of PyrroUdine and Piperidine Alkaloids from Tobacco. Journal of Organic Chemistry, 66, 6305-6312. 

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... 

H. Rapoport, Biosynthesis of the pyridine and piperidine alkaloids. The tobacco alkaloids. Abhandl. Deut. Akad. Wiss. Berlin, Kl. Ghem., Geol. Biol. Ill (1966) CA 66, 73203 (1967). 

There is no uniform classification for the A. In the literature divisions according to origin (examples Aconitum, Amaryllidaceae, Aspidosperma, cactus, Catharanthus, Cephalotaxus, Cinchona, coca, Corydalis, curare, Dendrobates, ergot, Erythrina, Iboga, Lycopodium, Maytenus, opium, Rauvol-fia, Senecio, Strychnos, tobacco, Vinca alkaloids, salamander, Solanum, Veratrum steroid alkaloids) in addition to divisions according to chemical structure (examples aporphine, benzylisoquinoline, bis-benzylisoquinoline, berberine, carboline, diterpene, inudazole, indole, indolizidine, isoquinoline, lupinane, macrocyclic, morphine, peptide, / -phenyl-ethylamine, piperidine, purine, pyridine, pyrrolidine, pyrrolizidine, quinoline, quinolizidine, quinucli-dine, spermine, spermidine, steroid, terpene, tro-pane, tropolone alkaloids) are used. 

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). 

Vojnich VJ, Mdth6 A, Szoke E, Gaal R (2012) Effect of Mg treatment on the production of Indian tobacco Lobelia inflata L.). Acta Horticulturae (ISHS) 955 125-128 Kursinszki L, Szoke E (2013) Characterization of piperidine alkaloids of Lobelia inflata L by liquid chromatography combined with electrospray ionization tandem mass spectrometry. J Chrom A 1318 (submitted)... 

Piperidine alkaloids found in Cdnium maailatum (poison hmlock) arxl Nico-tiana species (tobacco, tree tobacco) cause skeletal arthrogrypmis. 

Solenopsis (Diplorhoptrum) conjurata and some other thief ants contain indo-lizidines and/or piperidines (Tables I and II). (5Z,8 )-3-Heptyl-5-methylpyr-rolizidine (48) has also been shown to be contained in the thief ant Solenopsis xenovenenum (Table IV). The poison glands of Aphaenogaster fulva and A. tennesseensis contain the tobacco alkaloid anabaseine (8), which functions as an attractant in A. fulva (Table I) (26). 

Nomicotine, an organocatalyst studied by Dickerson and co-workers (Entry 5 [52, 58d], Appendix 7.B), reinforces the important principle that even catalysts from Nature can present problems when it comes to toxicity. The family of nicotinic receptor agonists (Figure 7.9) contains several chiral pyrrolidines and piperidines with the potential to act as asymmetric aldol catalysts. Nomicotine, which can be isolated from plants such as tobacco, or readily synthesized by demethylation of the maj or tobacco alkaloid nicotine, was investigated in some depth as an aldol catalyst by Dickerson and Janda in 2002 [52]. 

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... 

Lobelia or Indian tobacco consists of the dried leaves and tops of Lobelia inflata (Campanulaceae), an annual herb from the USA and Canada. Lobelia contains about 0.2-0.4% of alkaloids, of which the piperidine derivative lobeline (Figure 6.23) is the chief constituent. Minor alkaloids identified include closely related structures, e.g. lobelanine (Figure 6.23). The North American Indians employed lobelia as an alternative or substitute for tobacco (Nicotiana tabacum Solanaceae), and it is found that lobeline stimulates nicotinic receptor sites in a similar way to nicotine, but with a weaker effect. Lobeline has been employed in preparations intended as smoking deterrents. The crude plant drug has also long been used to relieve asthma and bronchitis, though in large doses it can be quite toxic. 

The enantioselective total syntheses of several piperidine and pyrrolidine alkaloids of tobacco were accomplished in the laboratory of J. Lebreton. ° In the final stage of the total synthesis of (S)-A/-methylanabasine, a one-pot Cbz-deprotection-hydrogenation-Eschweiler-Clarke methylation was carried out using a HCHO/MeOH/Pd(C)/H2 system at room temperature with an overall 88% yield. 

Piperidine-like alkaloid from Indian tobacco (Lobelia inflata). Partial agonist at nACh receptors and alters dopamine storage and release. 

Although Z-nicotine is the major alkaloid of tobacco, a number of other bases have been reported as occurring with it such as nicotimine, nicoteine, and nicotelline (259, 260, 261) to which Noga later added two more isonicoteine and nicotoine (261). It is now known that nicoteine was a mixture (262) and the homogeneity of nicotimine is extremely doubtful. The latter was considered to be 3 -pyridyl-2-piperidine, but its properties do not agree with those of that compound now known to be identical with anabasine. Furthermore, isonicoteine has been shown to be identical with 3, 2-dipyridyl (263). 

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). 

Thebaine, the methoxy derivative of morphine, is also a habit-forming substance, but its primary toxic effects are similar to those of strychnine, a convulsant poison, rather than narcosis. Also, there are alkaloids having different structures but similar toxic actions. Lobeline, a lobelia alkaloid, which has a piperidine nucleus, shows pharmacologic action similar (but less potent) to that of nicotine, a tobacco alkaloid that has a pyridine-pyrrolidine ring system. The structure, occurrence, physical properties, and toxicity of some important alkaloids are presented in the following sections. 

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). 

L. inflata (Indian tobacco) is indigenous to the Eastern and Central states of USA and Canada. The plant contains ca. 0.3% of alkaloids. The L. a. are 2,6-di-substituted piperidine derivatives. Among the ca. 20 L. a., lobeline is the major alkaloid. When administered parenterally (3-10 mg) lobeline stimulates respiration and was used in the past as a respiratory analeptic agent for asthma, collapse, and narcosis incidents. When taken orally it is rapidly degraded and thus not effective. Since lobeline potentiates the action of nicotine and induces nausea and revulsion it has been developed clinically in depot form in antismoking preparations. - The piperidine ring is biogenetically derived from lysine and the substituents from phenylalanine. 

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. 

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]. 

The pyridine and piperidine rings are found in many natural products. Examples are nicotine (the major alkaloid in tobacco, used as an agricultural insecticide and... 

Nicotinoids with Basic Pyrrolidine or Piperidine Moiety. Nicotinoids are (i) congeners of nicotine, usually minor alkaloids but the term also includes (ii) the principal tobacco alkaloid, nicotine itself. From the structural point of view the nicotinoids may be divided into five groups (Figs. 3.8 and 3.9) ... 

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