Alkaloids lobeline

The alkaloid lobeline (as derived from Lobelia inflata) bears a striking resem-blanee to nieotine, and both have similar chemical actions. This may extend to cancer treatment. Heinerman observes that the nineteenth century American herbalist... 

Lobeline.—The results of feeding experiments with DL-[2- C]lysine and dl-[2- Clphenylalanine in Lobelia inflata have shown that these amino-acids are both specific precursors for the alkaloid lobeline (13). In further experiments, DL-[3- C]phenylalanine, [3- C]cinnamic acid, and [3- C]-3-hydroxy-3-phenylpropionic acid [as (9)] have been found to be specific precursors for lobeline (13). These results are consistent with the anticipated pathway " to lobeline illustrated in Scheme 2, with benzoylacetic acid (10) as the intermediate which couples with A -piperideine to give the intermediate (11). The probability of 3-hydroxy-3-phenylpropionic acid (9) being an intermediate in lobeline biosynthesis is increased by the isolation of this acid from L. inflata ... 

Desymmetrization of meso-Diols. BTM-catalyzed de-symmetrization of meso-diol lobelanidine has been employed as the key step in an asymmetric synthesis of alkaloid lobeline (eq 6).5... 

Solid-phase extraction (SPE micro-columns) was efficient for the purification of alkaloidous solutions. Aliquots were passed through a pre-activated (by methanol than water) SPE cartridge (Supelclean LC-8 columns 500 mg, 3 mL, supplied by Supelco) which was then washed with water. Extraction was performed on a vacuum manifold processor (LiChrolut extraction unit Merck).The alkaloid (lobeline)-containing fraction was eluted from the tube with methanol. On the basis of the HPLC determination, the recovery of lobeline from the SPE step was total [40]. 

For identification of alkaloids of plant obtained by vegetative micro propagation, the LC-MS/MS quadropole with electrospray ionization method was very suitable. In plant cultivated on field, 52 alkaloids (lobeline and related piperidine alkaloids) were found and identified. Of them, as main component, was identified the 8-ethyl-lO-phenyl-lobelienonol isomer of molecular ion [M + H]" of miz 288 (Fig. 11.29), [52]. 

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). 

Contains alkaloids lobeline, lobeHdirte Toxic principle is coniine and related alkaloids Contains the quinolizidine alkaloid cytisine Contains cytisine, similar to Cymnocladus... 

Methylation of the secondary amine of aT-norlobelanine (52) affords lobelanine (53), a precursor of the alkaloid lobeline (54), which is obtained upon selective reduction of a single carbonyl group and is commonly applied as a smoking cessation aid [9]. 

Isolates from Indian tobacco Q obelia inflata L.), as a cmde mixture of bases, have been recognized as expectorants. The same (or similar) fractions were also used both in the treatment of asthma and as emetics. The principal alkaloid in T. inflata is lobeline (49), an optically active tertiary amine which, unusual among alkaloids, is reported to readily undergo mutarotation, a process normally associated with sugars. Interestingly, it appears that the aryl-bearing side chains in (49) are derived from phenylalanine (25, R = H) (40). 

Billing 7 has provided a scheme for distinguishing between the hemlock bases and other alkaloids, such as sparteine, nicotine and lobeline. 

The presence of alkaloids in Lobelia injlata, Linn., was first recorded by Proctor. Lobeline was prepared by Lewis as a basic oil from which Siebert made and analysed a series of salts and proposed the formula, CigHjsOjN. In 1921 Bohringer and Sohne protected a process for the isolation and separation of three alkaloids, a-, 3 and y-lobelines. In the same year Wieland published the first of a series of papers in which is described the isolation of several groups of alkaloids, to most of which constitutional formulae have been assigned and, in some cases, confirmed... 

Numerous methods for the alkaloidal assay of lobelia and its galenical preparations have been published and two recent critical surveys, by a special committee of the Society of Public Analysts and by Caulkin, indicate that the process of Markwell is satisfactory. Processes for the isolation and separation of the various alkaloids have been protected by patent. Balandin states that Lobelia sessiliflora contains less alkaloid than L. injiata but yields a high-quality lobeline. 

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. 

LELOBINE AND LOBININE GROUPS. These include the minor alkaloids of lobelia isolated from factory residues accumulated during the manufacture of lobeline. Their isolation and separation involve complicated processes of fractionation for which the original paper should be consulted. Their inter-relationships (Table A, p. 23 and general formula, I, p. 24) are similar to those among members of the lobeline group, but the effect of the presence of three or more asymmetric carbon atoms is more evident, thus there are already known six forms of the basic dihydric alcohol, lelobaiiidine. 

Isotoma longiflora. This Peruvian plant contains an alkaloid, m.p. 190°, forming a hydrochloride, m.p. 160°. Pharmacological results are recorded and it is suggested that the alkaloid resembles lobeline of which it may be a derivative (Sanchez, Rev. Med. expU, (Peru), 1945, 4, 284 Chem. Abstr., 1948, 42, 1350). 

The alkaloid sedamine has been prepared under physiological conditions too (318). Aldolization of the immonium salt 200, obtained by mercuric acetate dehydrogenation of (2S,8R)-(—)-sedamine (199), with benzoylacetic acid produces (2S,6R,8S)-(—)-8,10-diphenyllobelinol (i.e., (—)-lobeline) (201). This determines its absolute configuration (319, 320). 

Lobeline. The alkaloid lobehne, whose mechanism of action in unclear but that appears to have dopamine reuptake blockade and nicotinic receptor antagonist properties (Dwoskin and Crooks 2002), was evaluated in a double-bhnd, randomized, placebo-controUed, multicenter trial involving 180 ciga-... 

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. 

Lobeline (3), extracted from Lobelia inflate, interacts with the nicotinic receptor and could also be exploited to influence cholinergic function in AD. Other alkaloids such as sophoramine (4) and cytisine (5), found in members of the Leguminosae, also have nicotinic agonistic properties. ... 

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. 

The alkaloids which influence acetylcholine esterase activity are eserine, galan-thamine, nicotine, lobeline and tubocurarine. All of these alkaloids are very active. 

Drugs based on eserine, galanthamine, nicotine, lobeline and tubocurarine are also prominent. Two examples of drugs containing eserine are Antichohum and Pilo-Eserin. There are at least 20 different products based on this alkaloid. 

The tertiary natural cholinomimetic alkaloids (pilocarpine, nicotine, lobeline Figure 7-3) are well absorbed from most sites of administration. Nicotine, a liquid, is sufficiently lipid-soluble to be absorbed across the skin. Muscarine, a quaternary amine, is less completely absorbed from the gastrointestinal tract than the tertiary amines but is nevertheless toxic when ingested—eg, in certain mushrooms—and it even enters the brain. Lobeline is a plant derivative similar to nicotine. These amines are excreted chiefly by the kidneys. Acidification of the urine accelerates clearance of the tertiary amines. 

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 constitution of a number of alkaloids has not as yet been definitely established. Among these are aconitine from aconite, delphinine from larkspur, jervine and protojervine from veratrum viride, cevadine from sabadilla seed, lobeline from lobelia, the curare alkaloids from Chondro-dendron tomentosum, sanguinarine from sanguinaria, and many others. 

Meperidine (isonipecaine, Demerol , and Dolantin ) is the methyl ester of methyl-4-phenylpi-peridine-4 carboxylic acid. It is used in the form of its soluble hydrochloride. The piperidine nucleus is also present in many alkaloids, such as atropine or lobeline, which are not analgesics, as well as in morphine. 

Lobelia nicotianaefolia Heyne (Lobeliaceae) (XI, 462 XII, 488) Lobeline constituted 20% of the total alkaloids (103a). 

Active Constituents Lobeline -- 2-[6-(beta-hydroxy-phenethyl)-1-methyl-2-piperidyl] acetophenone -- and related alkaloids. 

Some alkaloids interfere with the assembly of microtubules (taxol, colchicine, maytansine), inhibit key enzymes such as adenylate cyclase (papaverine, theophylline, theobromine), activate neuromuscular systems involving ACH (physostigmine, coniine, nicotine), inhibit digestive processes (emetine, lobeline, morphine), modulate liver and kidney function (pyrrolizidine alkaloids, amanitine), and destabilize the blood and circulatory system (vinblastine, colchicine). 

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