Lupin alkaloids sparteine

Feeding experiments utilizing C-, N-, and H-labeled cadaverine (44) and lysine (24) in l upinus augustifolius a source of the lupine alkaloids (—)-sparteine (50, R = H,H) and (+)-lupanine (50, R = O), have been reported which lend dramatic credence to the entire biosynthetic sequence for these and the related compounds discussed above (41). That is, the derivation of these bases is in concert with the expected cyclization from the favored aH-trans stereoisomer of the trimer expected on self-condensation of the 1-dehydropiperidine (45). 

The lupin alkaloids sparteine (98) and lupanine (99) are both derived from lysine, and it is possible on the basis of past work that either one may be a precursor of the other.63 However, recent work suggests that they are derived by divergent pathways.64... 

The majority of the acute studies has been performed on the common lupin alkaloids sparteine and lupanine [39-41]. They both display moderate acute toxicity, the former being the more toxic one. The observed symptoms suggest that alkaloids cause neurological effects leading to loss of motor coordination and muscular control. The effects are generally reversible. 

Several lupin alkaloids have been derived from the unsaturated quinalozidine 433, that was obtained in the treatment of amine 431 with ortho-quinone 432. This quinone behaves as a model of topaquinone, the cofactor of copper-containing amine oxidases. The cyclization step involved a nucleophilic attack of the piperidine nitrogen of 431 onto a side-chain aldehyde function that is unmasked by the oxidative deamination. Quinolizine 433, when treated with dehydropiperidine, gave the oxime ether 434 that, on ozonolysis followed by reduction, afforded sparteine 10, presumably via the bis(iminium) system 435 (Scheme 102) <1996JOC5581>. 

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. 

Sparteine, lupanine, and other QA exhibit antiarrhythmic properties. Since only sparteine can be isolated easily from broom (Cytisus scoparius) it is the only lupin alkaloid that is commercially available and exploited in medicine as an antiarrhythmic drug. However, about 10% of all patients are unable to metabolize sparteine and suffer from sparteine intoxication. Because of these side effects and the availability of more reliable synthetic heart drugs, the use of sparteine in... 

Lupin Alkaloids.—The Ci5 lupin alkaloids, e.g. sparteine (9) and lupanine (10), are biosynthesized from three C5 units derived (as shown in Scheme 2) from lysine and... 

The most common group of alkaloids possessing a quinolizidine nucleus is that of the lupine alkaloids which can simply be classified as bicyclic (lupinine/epilupinine type), tricyclic (cytisine type) or tetracyclic, (sparteine/lupanine or matrine type). Fig. (23). This grouping is made according to structure complexity and without considering biosynthesis, as the detailed biosynthetic pathways are still not completely understood. 

The conformational study of sparteine derivatives has been of great interest due to their use as synthetic chiral auxiliaries and a brief account of the progress made in this area will be presented. A description of the newly isolated and characterised lupine alkaloids, as well as an updated review of the biological activity of these metabolites will be given. 

Ten of the 45 alkaloids that were gas chromatographed by Lloyd et al. in 19611 on a 2-3 % SE-30 on Chromosorb W column were lupine alkaloids. The bicyclic lupinine and the tricyclic sparteine, a-isosparteine and 13-hydroxysparteine were chromatographed at at column temperature of 160°C, the tricyclic cytisine, methylcytisine, methylcytisine-N-oxide and the tetracyclic lupanine, 13-hydroxylupanine and matrine at 204°C.The retention times of the alkaloids are listed in Table 7.1. 

In vitro tissue and cell cultures of lupin plants are not appropriate systems for the study of biosynthesis of lupin alkaloids, because the production ability by in vitro culture is rather low, i.e., 10 2 to lO times compared with that of differentiated plants. The production of the alkaloids of lupinine- and sparteine-groups by cell culture have been reported by us [59] and by Wink s group [60]. We have also successfully produced matrine in green callus culture and in multiple shoots of Sophora flavescens [61]. The producibility of matrine was positively correlated with the chloroplast formation. This indicates that the formation of carbon skeleton of matrine-type alkaloids also likely takes place in chloroplasts in plant cells as postulated in that of sparteine-type alkaloids [62]. 

Since lupin seeds are used in some areas in cattle feeding, it is of practical as well as theoretical interest to determine the stage at which the seeds will be rich in the alkaloidal material responsible for toxicity. It has also been important to devise methods for the removal of alkaloids from the seeds so that the detoxified or debittered material can still be used as feed (111). Extraction procedures which accent the recovery of non-alkaloidal material have less interest to the alkaloid chemist than those which provide for the isolation of the pure organic bases. Given below are typical examples of the extraction procedures employed for the isolation of the lupin alkaloids lupinine, cytisine, Z-sparteine, d-lupanine, and anagyrine. The methods selected are representative of those utilized for the isolation of the less abundant or well-known lupin alkaloids as well. These methods are also representative of the different quantities of materials which are handled. One of the methods was selected (for anagyrine) to indicate some of the complexities of separation when there are a number of alkaloids present in a plant, rather than only one main alkaloidal constituent. The techniques of fractional distillation of the bases, fractional crystallization of alkaloid salts, such as perchlorates and picrates, and extractions dependent upon differential solubility have been employed for the isolation of pure individual alkaloids from a mixture. 

Oxysparteine was also the intermediate which furnished conclusive proof of the ring structure of all the Cw lupin alkaloids. Clemo, Morgan, and Raper in 1936 (260) announced the synthesis, from non-alkaloid starting materials, of a compound with structure XCV and established the identity of this compound with the d/-oxysparteine obtained by alkaline ferricyanide oxidation of dZ-sparteine. The s3Tithesis of dZ-oxy-sparteine (XCV) was accomplished as outlined below. The Claisen condensation of ethyl 2-pyridylacetate (XCVI) with ethyl orthoformate... 

On the basis of evidence and knowledge presently accumulated, it has been possible to assign absolute stereochemical structures to the members of the C16 family of lupin alkaloids. The arguments of Marion and Leonard (320) rest upon (a) the structural similarity but configurational difference between rings B and C in sparteine and its derivatives (278), (b) the study of accurate scale molecular models, and (c) the recognized surface nature of the catalytic hydrogenation process (327), as applied to certain of the alkaloid interconversions. Consistent with... 

Table 1 Isolation of alkaloids of the lupine-cytisine-sparteine-matrine-Ormosxz. group...

Lupanine lupin Lupinus quinolizidine alkaloids sparteine... 

Lupanine and other lupin alkaloids show moderate toxicity in vertebrates. In mammals, acute intoxications with sparteine, lupanine, or angustifoline cause convulsions, shaking and trembling, and death from respiratory and cardiac arrest [15]. 

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