Quinolizidine alkaloid spartein

Among quinolizidine alkaloids, sparteine and its stereoisomers have been studied in detail by X-ray analysis (42-50). It was demonstrated that proper conformation was not reorganized in monohydrates (42), diperchlorates (43), or methyliodides of a-isosparteine (11) (53). Unlike in the case of a-isosparteine, in spareteine diperchlorate rings C/D appear to have a boat-chair conformation (44-46). On the basis of spectroscopy data a cis conformation for sparteine methyliodide (12) was proposed (57,52). However, radiographic examination (53) of this compound showed it to have the trans conformation (13). 

Voltage-gated K+ channels are critical to transmembrane potential- and Ca2+-mediated signalling. Voltage-regulated K+ channels are critically involved in action potentials as described above and such channels are blocked by the legume quinolizidine alkaloid sparteine (lupinidine) as well as by various synthetic psychoactive compounds with disparate effects such as amitryptiline, chlorpromazine, imipramine and phencyclidine. 

Lupanine lupin Lupinus quinolizidine alkaloids sparteine... 

The synthesis pathway of quinolizidine alkaloids is based on lysine conversion by enzymatic activity to cadaverine in exactly the same way as in the case of piperidine alkaloids. Certainly, in the relatively rich literature which attempts to explain quinolizidine alkaloid synthesis °, there are different experimental variants of this conversion. According to new experimental data, the conversion is achieved by coenzyme PLP (pyridoxal phosphate) activity, when the lysine is CO2 reduced. From cadeverine, via the activity of the diamine oxidase, Schiff base formation and four minor reactions (Aldol-type reaction, hydrolysis of imine to aldehyde/amine, oxidative reaction and again Schiff base formation), the pathway is divided into two directions. The subway synthesizes (—)-lupinine by two reductive steps, and the main synthesis stream goes via the Schiff base formation and coupling to the compound substrate, from which again the synthetic pathway divides to form (+)-lupanine synthesis and (—)-sparteine synthesis. From (—)-sparteine, the route by conversion to (+)-cytisine synthesis is open (Figure 51). Cytisine is an alkaloid with the pyridone nucleus. 

This pathway clearly proves that the first quinolizidine alkaloid to be synthesized is (—) lupinine (two cycling alkaloids) and subsequently both (+)-lupanine and (-)-sparteine. This is a new approach to the synthesis of this type of alkaloids because in the older literature just four cycling alkaloids (lupanine and sparteine) were mentioned as the first synthesized molecules . In the cadaverine conversion, the participation of diamine oxidase is more reliable than the oxosparteine synthase mentioned by some older studies °. 

The X is transformed in two directions (—)-sparteine and (-l-)-lupanine, the two basic quinohzidine alkaloids which occur in nature and which have an important role in the ecosystem. The (—)-sparteine is transformed by the cleavage of the C4 unit to (-l-)-cytisine, a three-cycle quinolizidine alkaloid with a pyridon nucleus, and from this step to the other pyridon quinolizidine alkaloids (P, Pj). The (-l-)-lupanine converts to the lupanine derivatives, angustifoline, a-isolupanine and 13a-hydroxylupanine (P) (Figure 54). 

One of the most important tetracyclic quinolizidine alkaloids with a quinolizidine nucleus is lupanine, which is in fact 2-oxo-lla-sparteine. In absolute configuration, lupanine is (-I-)-lupanine with a molecular weight of 248 and melting point of 127 Lupanine occurs in L. polyphyllus, L. albus and... 

This group of alkaloids has a pyridone nucleus and generally takes the tetracyclic or tricyclic form. The a for pyridone alkaloids is L-lysine, while the j8, q> and X the same as for other quinolizidine alkaloids. Quinolizidine alkaloids containing the pyridone nucleus are the P from the (—/-sparteine by cleavage of the C4 unit. The first quinolizidine alkaloid with the pyridone nucleus is tricyclic cytisine, which converts to four cyclic alkaloids. In this synthesis the anagyrine, the most poisonous quinolizidine alkaloid with a pyridone nucleus, has its own synthesis pathway. 

The first method of alkaloid analysis was developed in 1805, in the case of morphine. This method of isolation, with minor and major variations, is still used today. By this method, the first quinolizidine alkaloids were also extracted sparteine in 1851, lupinine in 1865 and lupanine 2 years later. At the beginning of the 20th century, the extraction and determination of total quinolizidine alkaloids in the same analysis (common) was carried out by Jurkowski , Nowotndwna, Trier272, ivanov °, Sengbusch , Lukaszewicz , Wuttke . Reifer and Niziolek and Wiewiorowski and Skolik initiated research in which the sum of the contents of the different and separate alkaloids is the total alkaloid content. The method of isolation of quinolizidine alkaloids was developed next by Wysocka et and Wysocka and Przybyl . ... 

The idea of calorimetry is based on the chemical reaction characteristic of molecules. The calorimetry method does not allow absolute measurements, as is the case, for example, with volumetric methods. The results given by unknown compounds must be compared with the calibration curve prepared from known amounts of pure standard compounds under the same conditions. In practical laboratory work there are very different applications of this method, because there is no general rule for reporting results of calorimetric determinations. A conventional spectrophotometry is used with a calorimeter. The limitations of many calometric procedures lie in the chemical reactions upon which these procedures are based rather than upon the instruments available . This method was first adapted for quinolizidine alkaloid analysis in 1940 by Prudhomme, and subsequently used and developed by many authors. In particular, a calorimetric microdetermination of lupine and sparteine was developed in 1957. The micromethod depends upon the reaction between the alkaloid bases and methyl range in chloroform. 

Quinolizidine Alkaloids.—Biosynthesis of quinolizidine alkaloids, e.g. sparteine (28), is from lysine (15) by way of cadaverine (16), as shown in Scheme 4. Three cadaverine units (as indicated by the thickened bonds) are required for the construction of alkaloids such as sparteine (28).10 Although something has been discerned about the biosynthetic relationships of various quinolizidine alkaloids, the nature of early intermediates beyond cadaverine has remained quite elusive.10 Exciting new results obtained with crude enzyme preparations from cell suspension cultures of Lupinus polyphyllus indicate why this is so. 

Hyoscyamine, scopolamine, and other tropane alkaloids (AA) acetylheliosupine and some other pyrrolizidine alkaloids arecoline (A) berbamine, berberine, and other isoquinoline alkaloids dicentrine and other aporphine alkaloids strychnine, brucine cryptolepine (AA) sparteine and other quinolizidine alkaloids (A) pilocarpine (A) emetine himbacine and other piperidine alkaloids (A) imperialine (AA) muscarine (A)... 

Aconitine and related diterpene alkaloids (A) veratridine, zygadenine, and related steroidal alkaloids (A) ajmaline, vincamine, ervatamine, and other indole alkaloids (AA) dicentrine and other aporphine alkaloids (AA) gonyautoxin (AA) paspalitrem and related indoles (AA) phalloidin (AA) quinidine and related quinoline alkaloids (AA) sparteine and related quinolizidine alkaloids (AA) saxitoxin (AA) strychnine (AA) tetrodotoxin (AA)... 

Bitterness varies with the chemical structure of an alkaloid. With the quinolizidine alkaloids (QAs) the following scale was assessed for man Mean detection levels are 0.00085% for sparteine, 0.0021% for lupanine, and 0.017% for hydroxylupanine (503). Whereas we know a few parameters of olfactory qualities in Homo sapiens, often much less or hardly anything is known for most other vertebrates. 

Cytisus scoparius (Scotch broom) contains the toxic alkaloid sparteine and related quinolizidine alkaloids, such as isosparteine and cytisine. Sparteine has been used as a marker of drug metabolism by CYP2D6 (28) and is covered in a separate monograph. 

Sparteine is a major quinolizidine alkaloid found in a variety of plants ... 

Among the known quinolizidine alkaloids of natural origin, only a few are of pharmacological or therapeutic relevance. In the period of time covered by this review, sparteine and cytisine were the only two natural quinolizidines that were reported for their biological importance. 

Sarothamnus catalaunicus Webb has already yielded several quinolizidine alkaloids, namely, (— )-sparteine, (+ )-lupanine, angustifoline, 13-hydroxylupa-nine, cineverine, and catalauverine.13 More recently, the branches of this species have been shown to contain sarodesmine (8), which was identified as the 3,4,5-trimethoxybenzoate of 13-hydroxylupanine.14 Continuing their investigations... 

Alkaloids which modulate ion channels are tabulated in Table 10. Voltagegated Na+ channels are a target for several steroidal alkaloids, (e.g., batrachotoxinin, samandarine, veratrine, veratridine and zygadenine), indole alkaloids (e.g., ajmaline), aporphines (e.g., dicentrine, liriodenine), quinoline alkaloids (quinine, quinidine), quinolizidine alkaloids (e.g., sparteine, lupanine), and furthermore, for alkaloids present in animals or venoms (e.g., chiriquitoxin, i-conotoxins, dibromosceptrine, gonyauxtoxins, histrionicotoxins, pumiliotoxins, saxitoxin and tetrodotoxin). 

Quinolizidine alkaloids (QA), such as lupanine, sparteine or cytisine are produced by many members of the Leguminosae. QA are bitter for many animals (and plants producing them are therefore avoided as food)... 

Quinolizidine alkaloids, such as sparteine, lupanine and cytisine are relatively weak inhibitors at this target (they strongly affect ACh receptors and Na+ channels see Tables 3-15). The stages which are inhibited are the loading of aminoacyl-tRNA with amino acids and the elongation step. The inhibitory activity was visible in heterologous systems, but protein biosynthesis in the producing plants (here lupins) was not affected [23]. 

Quinolizidine Alkaloids.—Previous results demonstrate that the quinolizidine skeleton in its entirety derives from lysine.Further research has indicated that lysine is a precursor of all the alkaloids of this type in five species of Leguminosae. From the levels of activity observed in the individual alkaloids it was concluded that saturated alkaloids are precursors for those with a pyridone ring. This was supported by the observation that label from radioactive sparteine (24) and lupanine (25) appeared in more highly oxidized alkaloids. (This compares with a similar situation in the biosynthesis of matrine-type alkaloids. ) A metabolic grid for the biosynthesis of quinolizidine alkaloids from lysine was proposed, based on these results,... 

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