Alkaloids piperidine, lobelia

Several plants produce milk juice sequestered in laticifers in several plant genera alkaloids are mainly stored in latex vesicles, such as isoquinoline alkaloids in Papaver and Chdidonium, or piperidine alkaloids in Lobelia. If herbivores wound such a plant, the latex will spill out and the herbivore will immediately be confronted with alkaloids. Since most of them are strong poisons, a deterrent effect is usually achieved. Another strategic way to store alkaloids is their sequestration in epidermal vacuoles or in trichomes. These tissues have to ward off not only herbivores (especially small ones) but also microorganisms in the first place. Several classes of alkaloids have been found in epidermal tissues, such as quinohzidine and tropane alkaloids [2,3]. 

A comprehensive review article on the synthesis of piperidines by Buffat was published in 2004. The review covers many different methodologies applicable to simple piperidines and complex natural products. Pertinent literature through early 2003 is included <04T1701>. A review on the history, chemistry, and biology of the alkaloids from Lobelia inflate by Felpin and Lebreton includes useful information on the synthesis of piperidine alkaloids, with an emphasis on asymmetric methods <04T10127>. 

Ma, Y, and M. Wink. 2008. LobeUne, a piperidine alkaloid from Lobelia can reverse P-gp dependent multidrug resistance in tumor cells. Phytomedicine 15(9) 754-758. 

Resting, J.R., I.L. Tolderlund, A.F. Pedersen, et al. 2009. Piperidine and tetrahydropyridine alkaloids from Lobelia siphilitica and Hippdmnm longiflora. J. Nat. Prod. 72(2) 312-315. 

LobeHa aikdoids. Name for piperidine alkaloids from Lobelia inflata (Lobeliaceae) and some related species. 

Biological Activity of Tropane Alkaloids Distribution of Tropane Alkaloids Piperidine Alkaloids Alkaloids from Piper Species Piperine Alkaloids Involving Condensation with Acetate/Malonate Sedum Alkaloids Lobelia Alkaloids Lycopodium Alkaloids Piperidine Alkaloids in Insects Polyketide-Derived Alkaloids Coniine... 

HPLC-MS/MS Characterization of Piperidine Alkaloids of Lobelia inflata... 

Kursinszki L, Ludanyi K, Szoke E (2008) LC-DAD and LC-MS-MS analysis of piperidine alkaloids of Lobelia inflata L. (in vitro and in vivo). Chromatographia 68 27-33 Balvanyos I, Kursinszki L, Szoke E (2001) The effect of growth regulators on the biomass formation and lobeline production of Lobelia inflata L. hairy root cultures. Plant Growth Regul 34 339-345... 

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)... 

In addition to lupines, poison-hemlock and Nicotiana spp., other plant species of the genera Genista, Prosopis, Lobelia, Cytisus, Sophora, Pinus, Punica, Duboisia, Sedum, Withania, Carica, Hydrangea, Dichroa, Cassia, Ammondendron, Liparia, and Colidium contain potentially toxic and teratogenic piperidine alkaloids. Many plant species or varieties from these genera may be included in animal and human diets (Keeler and Crowe, 1984). 

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. 

Allosedamine 157 is a relatively simple piperidine alkaloid which was isolated more than 60 years ago by Wieland and co-workers from Lobelia inflate. It has good activity against respiratory disorders such as asthma, bronchitis, and pneumonia. The key step of the current synthesis (Scheme 29) is an RCM of enone ester 155 which closes the... 

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. 

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

Lobelia tupa Known in Chile as tupa or tabaco deldiablo, Mapuche Indians have been reported to smoke the leaves of this plant as an inebriant (Duke 1985 Schultes Hofmann 1980). Piperidine alkaloids not known to be psychoactive are found in this plant, although lobeline is said to exert a nicotine-like activity. Lobelia inflata was used ceremonially by North American Crow Indians, and in love magic by Mesquakie and Pawnee Indians (IGndscher 1992). 

Piperidine alkaloids occur in only a few species of higher plants. However, (S)-pipecolic acid 3 [121] is widely distributed in higher plants, microorganisms and animals. Lobeline 4 is the main constituent of lobelia alkaloids (Lobelia inflata, Campanulaceae). It is a respiratory stimulant in mammals. Pi-perine 5 is the active ingredient in black pepper (Piper nigrum). On hydrolysis it furnishes piperic acid 6 and piperidine (hence its name) [122] ... 

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 S. a. are formed biogenetically from lysine via enzyme-bound intermediates. The side chain originates from phenylalanine. Sedamine is accompanied by structurally related piperidine alkaloids such as ( )- pelletierine and 2,6 substituted piperidines of the Lobelia alkaloid type (including sedinine, seda-crine) The acute toxicity of the S. a. is low, unambiguous pharmacological activities have not yet been confirmed. ... 

Lobelia inflata (Campanulaceae) grows wild in the U.S.A., the eastern and central part of Canada, and Kamchatka. The leaf has been used by Native Americans as an emetic since ancient times. From this plant, a large number of piperidine and Af-methylpiperidine derivatives were obtained, and the main alkaloids are lobehne, lobelanine, and lobelanidine [1,2]. 

Piperidine alkaloids a group of alkaloids containing the piperidine ring system. Simple P.a. are the alkyl substituted piperidines which occur sporadically. The other P.a. are classified according to their origin, e.g. Coninm alkaloids (see), Punica alkaloids (see), Sedum alkaloids (see) and Lobelia alkaloids (see). These various groups are structurally different and have different mechanisms of biosynthesis. Other P. a. are found in water lilies, and are biosynthesized from mevalonic acid (see Nuphara alkaloids). A de-hydropiperidine structure is present in the Areca alkaloids (see) and the Betalains (see). 

The biosynthesis, occurrence, and biological activities of piperidine alkaloids arising from lysine have been studied Punica granatum. Piper species, and Lobelia inflata). The isolation process, chromatographic purification/analysis, and structure elucidation of the significant alkaloids are discussed. 

Biological activities biosynthesis of piperidine alkaloids HPLC and LC-MS/MS Lobelia inflata lobeline and their derivates pelletierine Piper nigrum piperine Punic a granatum... 

While for developing of simple piperidine alkaloids, e.g., pelletierine (Punica granatum), piperine (Piper nigrum et longum), and lobeline (Lobelia inflata), only one molecule of lysine is necessary, for quinolizidine alkaloids - e.g., lupinine (Lupinus luteus), sparteine of antiarrhythmic activity (Sarothamnus scoparius), and cytisine of respiratory stimulant effect (Laburnum species) - two molecules of lysines are indispensable. It was also proved that lycopodine (Lycopodium tristachyum, clubmoss) of quinolizidine structure has no polyketide origin, but it is a modified dimer of pelletierine, which, in turn, is derivable from lysine and acetate. 

In this chapter, we intensively studied the Punica, Piper, and Lobelia piperidine alkaloids. These plants and their main alkaloids are undoubtedly known and used in therapy for ages, but at present, numerous scientific results were also bom on their biological activities and pharmacological and clinical tests further, new alkaloids were isolated and semisynthetic analogues prepared, which could be important in the modem phytotherapy. 

The piperidine ring - the core of Lobelia alkaloids - is derived generally from lysine but their biosynthetic pathways are depentent on the type (phenolic or aliphatic) of side chains, although the piperidine core seldom could be derived from nicotinic acid (similarly to pyridine alkaloids), e.g., in case of anatabine. 

In biosynthesis of Lobelia alkaloids, the two basic compounds (direct precursors) are A -piperideine and benzoylacetic acid. A -piperidine is derived from lysine via two pathways direct from the cadaverine or the 5-aminopentanal, a cadaverine derivate (Fig. 11.17). 

Biosynthesis of Lobelia Alkaloids with Core of A -Dehydropiperidine The biosynthetic pathways of Lobelia alkaloids in which the core is A -dehydropiperidine (tetrahydropyridine) ring instead of piperidine have not been studied, except of the anatabine. 

The Lobelia alkaloids were first detected by Procter in 1850. At the begiiming of the twentieth century, Wieland and Scheuing isolated the first alkaloids from L. inflata. The most important alkaloid of the family Lobeliaceae is lobeline, which is an a, ai-disubstituted piperidine. Further, other alkaloids of L. inflata have been isolated, with their structures described [29, 34, 35]. 

The fragmentation of the molecular ion at m z 354 (Peak d. Fig. 11.27d) led to daughter ions, only two at m z 188 and 84. The ion at m z 188 might be explained by a neutral loss of 3-hydroxy-3-phenylpropanoic acid from its ester form resulting in dehydroxylated norallosedamine. This acid has been isolated from L. inflata and is considered as an intermediate in the biosynthesis of the phenyl-2-hydroxyethyl side chains of lobelia alkaloids. A possible fragment loss of 104 Da at m z 84 (188-84) can correspond to the removal of dehydroxylated phenyl-2-hydroxyethyl unit. Further, the ion at mJz 84 can be an indicator of that the parent piperidine ion was... 

Piperidine Alkaloids in Culture of Lobelia inflata Under In Vitro, Greenhouse, and Field Conditions... 

L. inflata L. is a traditional medicinal plant native to North America. It contains several piperidine alkaloids. The main alkaloid is lobeline which has a stimulatory effect on the respiratory center and it is applied in the cases of asthma, gas- and narcotic-poisoning. Thus, lobeiine is currently the subject of renewed interest for the treatment of drug abuse and neurological disorders, like Alzheimer s or Parkinson s disease, which pose an important public health problem in industrial countries. As lobeiine can act as a competitive nicotinic receptor antagonist, it is frequently used in antismoking preparations. Interest in Lobelia alkaloids, and in particular (-)-lobeline, the most active of them, has increased in recent years due to their activity on the central nervous system (CNS). 

In Lobelia inflata, two types of piperidine alkaloids were detected alkaloids of phenolic side chaines, as lobeline, lobelanine, norlobelanine, sedamine, and the dimer lobinaline further, alkaloids of aliphatic side chains diethyllobelidiol and methyl-ethyllobelidiol. It is important to mention that lobelane and nor-lobelane as... 

Sophora species [Leguminosae]) and the piperidine alkaloid lobeline (37) (from Lobelia inflata L. [Campanulaceae]), which have high affinity for 4p2 nAChRs lobeline also improves learning and is anxiolytic in vivo [137, 150, 151] (Scheme 42.9). Cytisine and derivatives may also be of therapeutic interest for PD (see Sect. 4). Huperzine A and tacrine hybrid structures (huprines) are also under investigation as nAChR agonists for AD, in addition to their documented ChE inhibitory and Mi mAChR agonistic properties [10] (see Sect. 2.2). 

Lobelia alkaloids, 320, 322 Lobelia piperidine alkaloids, 305 Lobelidine, 328... 

Allosedamine (113) and (+)-sedamine (119), two piperidine alkaloids isolated from Lobelia inflate, have been used for the treatment of respiratory disorders such as asthma, bronchitis, and pneumonia. While several racemic syntheses have been reported, there are much less asymmetric ones. An enantioselective route to (—)-aUosedamine (113) was developed by Raghaven et al, which commenced with addition of lithium compound 110 to the imine 109 providing the separable aUyUc amine 111 as a 3 1 mixture of diastereoisomers (Scheme 2.27) [45, 46). Six... 

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