Lobelanine

The carbonyl groups in the diketo- and keto-aleohol bases are not readily detected by the usual reagents and as these bases can be reduced to the dihydrie alcohols, it was assumed at first that lobeline and lobelanine contained one and two ether linkages respectively and formulse based on this assumption, and satisfying the other experimental evidence then available, were put forward by Wieland, Schopf and Hermsen, of which that for lobeline (II) may be quoted as an example. 

All five alkaloids must have the same nuclear structure since lobeline is convertible into lobelanidine by hydrogenation and into lobelanine by oxidation, and worlobelanidine and worlobelanine yield lobelanidine and lobelanine respectively on A-methylation. 

All five alkaloids yield acetophenone usually on heating dry, alone or in presence of a catalyst. Lobelanine hydrochloride on distillation with zinc dust produces more than one molecular proportion of acetophenone. 

Lobelanine dioxime, obtainable in poor yield, undergoes a Beekmann transformation into the dianilide of l-methylpiperidine-2 6-diaeetie aeid (lobelinie aeid (HI) ). On oxidation by ehromie aeid in sulphurie aeid lobelanine furnished l-methylpiperidine-2 6-dicarboxylic acid (scopolinic acid (IV)) and benzoic acid. 

Seheuing and Winterhalder treated 2 6-distr3rrylpyridine tetra-bromide with potassium hydroxide in alcohol, so producing 2 6-di-)3-phenylacetylenylpyridine (XI) which by the action of 50 per cent, sulphuric acid was converted into 2 6-diphenacylpyridine (XII), and this, on hydrogenation in presence of platinic oxide, barium sulphate and methyl alcohol, was reduced to 2 6-di-(6-hydroxy-(6-phenylethylpyridine, and the hydrochloride of this, on similar catalytic hydrogenation, yielded worlobelanidine (XIII). This can be methylated to lobelanidine, from which in turn dMobeline and lobelanine can be obtained. 

The A-methyl bases may be reached more directly by converting 2 6-di-(6-phenylacetylenylpyridine (XI) metho-p-toluenesulphonate, by treatment with slightly diluted sulphuric acid at 125°, into 2 6-diphenacylpyridine (XII) metho-p-toluenesulphonate. This, on direct hydrogenation, gives, with 3 mols. of hydrogen, lobelanine (VIII), or, with 5 mols. of hydrogen, lobelanidine (XIII NH— NMe). 

Schopf and Lehmann found that lobelanine could be synthesised by keeping at 25° a mixture of glutardialdehyde, methylamine hydrochloride and benzoylacetic acid in a buffered solution. The best yield was obtained at pH 4-5, and appeared to be complete in forty hours. At pH 7 or 9, 11 or 13, the yield was very small. This synthesis under physiological conditions is represented as occurring in accordance with the following scheme —... 

The methods of investigation used are the same in principle as those used successfully with the diketo-base, lobelanine (p. 24) in the lobeline series. 

Schopf and Lehmann synthesised by similar methods, which are referred to later, tropinone, -pelletierine and lobelanine These syntheses illustrate the dependence of yield on the pH of the reaction mixture, as the following table for yields of lobelanine hydrochloride shows. -—... 

Parker, W, Raphael, R.A., Wilkinson, D.l. (1959) Acetylenic Routes to Tropinone, pseudo-PeUetierine, and Lobelanine. Journal of the Chemical Society, 2433-2437. 

Lobelia contains 14 alkaloids, of which lobeline is the most significant (figure 4.13). Other alkaloids include lobelanine, lobelanidine, norlobelanine, and isolobinine. Another relevant chemical that is isolated from the leaves of lobelia is beta-amyrin palmitate. 

Alkaloids with the piperidine nucleus, such as pelletierine (Punica grana-tum), lobelanine Lobelia inflata) and piperine Piper nigrum), have a typical biosynthesis pathway. It starts with L-lysine and continues via cadaverine (biogenic amine), A -piperideine and A -piperidinium cations and lobelanine, to be synthesized as lobeline. Piperine is synthesized from A -piperideine via piperidine (Figure 49). For the transformation from A -piperideine to A -piperideine cation, the residue from acetyl-CoA is needed, together with SAM activity in the transformation to lobelanine. Piperine is synthesized from piperidine through the formation of amide. 

Figure 49. Diagram of the pelletierine, lobelanine and piperine synthesis pathway.

Lobelia chinensis L. L. pyramidalis Wallich. L. sessilifolia Lambert Ban Bian Lian Sha Gen Cai (Lobelia) (whole plant) Lobeline, lobelanine, lobelanidine, isolobelamine. (Lobeline has been approved by the FDA to curb the tobacco habit).33-50-71 This herb may be toxic. Diuretic, increase respiration via stimulation of carotid chemoreceptors. Treat snakebites, insecticide, reduce swelling, depurative, antirheumatic, antisyphilitic. 

Condensation reactions of aniline and of other bases with aromatic aldehydes to give Schiff s bases are accelerated by ultraviolet light in buffered media. For example, o-phenylenediamine reacts with formic acid to yield benzimidazole and acetylacetone reacts with guanidine to form 2-amino-4,6-dimethylpyrimidine.162 Similarly, lobelanine is formed by the photocondensation of glutaraldehyde, benzoylacetic acid, and methylamine hydrochloride.163... 

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. 

Anabasine (3-(2-piperidinyl)-pyridine) from Mcotiana and Duboisia species (Solanaceae) is an nACh-R agonist used to discourage tobacco smoking as is the JV-methylated tricyclic piperidine (—)-lobeline from Lobelia species (Campanulaceae). Lobeline-related compounds from Lobelia species include the bicyclic jV methyltetrahydropyridines isolobinine and lobinine and the tricyclic jV-methylpiperidines lobelanine and lobelanidine. Anabasine-related compounds include anatabine (2-(3-pyridyl)-l,2,3,6-tetrahydropyridine) from M tabacum and (+)-ammodendrine (jV-acetyltetrahydroanabasine) from Ammodendron and Sophora species (Fabaceae). 

Lobelia alkaloids, e.g., lobelanine (140), can easily lose one of the side chains. The primary degradation product [141] is further cleaved by a McLafferty rearrangement to [142]. Other key fragments corre-... 

Keywords A-84543 A-85380 ABT-089 ABT-418 ABT-594 Aminoethoxypyridines Anabaseine Anabasine Chloronicotine, 6- Cotinine Cytisine Dihydro-P-erythroidine DMXB Epibatidine GTS-21 Isonicotine Lobelanidine Lobelanine Lobeline Metanicotine Myosmine Nicotine Nicotinoids Nornicotine SIB-1508Y SIB-1553A SIB-1765F Tetrahydropyrido[3,4-rf]azepines... 

Ligand-receptor interactions, 287 Lobelanidine, 103 Lobelanine, 103 Lobeline, 103 Louis Pasteur, 79... 

Lobelanine (242) and lobelanidine (238) blocked nicotine-induced seizures in rats (ED50 = 25 nmole each) [518]. Lobelanidine was found to be a competitive inhibitor of pea diamine oxidase (Ki = 0.36 mM) 242 was inactive [453], Both 242 and 238 were recently synthesized and 238 was found to be a respiratory stimulant [536]. 

Lobeline (piperidine ring system) isolobinine (dehydro, piperidine ring) m.-lobelidine, lobelanine... 

In contrast to the biosynthesis of many other piperidine alkaloids, the incorporation of [2- C]lysine into lobeline (13) was found to be symmetrical, i.e. C-2 and C-6 were equally labelled. Symmetrization of the label could occur on formation of lobelanine (12), a known late precursor, or at a possible earlier intermediate,... 

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