Lupine alkaloids lupinine

Hypusine (N -(4-amino-2-hydroxybutyl)lysine) occurs in mammalian initiation factor 4D, which is utilized in protein S5mthesis (Chapter 29) and is formed by transfer of the 4-carbon butylamine group from spermidine to a lysine side chain followed by hydroxylation. The lupine alkaloid lupinine is formed from two C5 units of cadaverine which arises by decarboxylation of lysine. Silaffins (pp. 178, 1381) also contain modified lysines. 

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. 

Alkaloid metabolism in lupine was proved by Wink and Hartmann to be associated with chloroplasts (34). A series of enzymes involved in the biosynthesis of lupine alkaloids were localized in chloroplasts isolated from leaves of Lupinus polyphylls and seedlings of L. albus by differential centrifugation. They proposed a pathway for the biosynthesis of lupanine via conversion of exogenous 17-oxosparteine to lupanine with intact chloroplasts. The biosynthetic pathway of lupinine was also studied by Wink and Hartmann (35). Two enzymes involved in the biosynthesis of alkaloids, namely, lysine decarboxylase and 17-oxosparteine synthetase, were found in the chloroplast stoma. The activities of the two enzymes were as low as one-thousandth that of diaminopimelate decarboxylase, an enzyme involved in the biosynthetic pathway from lysine to diaminopimelate. It was suggested that these differences are not caused by substrate availability (e,g., lysine concentration) as a critical factor in the synthesis of alkaloids. Feedback inhibition would play a major role in the regulation of amino acid biosynthesis but not in the control of alkaloid formation. 

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. 

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. 

Lupin alkaloids can be classified into seven structural groups according to the carbon skeleton and the oxidative states (Fig. 1). The alkaloids of lupinine- and... 

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]. 

Lung carcinoma (A-549), 3479 Luotonin A, 658 Lupanine, 383, 1177 Lupin alkaloids, 382 Lupinine, 389 Lupinus, 383... 

Figure 1.13. Degradation of quinolizidine alkaloids A—general structure. B—end product alkaloids, and C— products derived from alkaloids. The structure of lupine alkaloids four ring— sparteine type three ring—cytisine type two ring— lupinine type laige hollow arrow— most common oxidation and hydroxylation arrows from parallel lines— most common dehydrogenation site.

Some plants accumulate alkaloids with very different chemical structures which are nevertheless related biosynthetically. In some cases the biosynthetic route may be branched, but in some it is rather clear that the more complicated structures arise from the simpler molecules. The latter condition is encountered in lupines. While the majority of alkaloids are of a coupled quinolizidine structure, two uncommon alkaloids, lupinine and epilupinine, are of a simple quinolizidine structure. The idea that lupinine is a precursor of sparteine, i.e., a bisquinolizidine, was first proven by experiments in which radioactive lupinine was fed to the plants and radioactive sparteine and its derivatives were isolated (Schuette, 1960 Nowacki et al.y 1961). In this study, varieties of Lupinus luteus from Palestine, Portugal, and central Europe were tested. There were plants that produced only one major alkaloid, either sparteine or lupinine however, the hybrid plants which produced sparteine also produced a small amount of lupinine. Consequently, it was a typical example of intermediate inheritance. The F2... 

In crosses of yellow lupines with lupinine as the major alkaloid with plants bearing only sparteine, the Fi plants had both alkaloids and in Fa a segregation into five groups was observed, the extreme with only one alkaloid comprising each about Viq of the Fa generation. The rest were... 

Figure 5.4a. Effect of lupine alkaloids on peanut plants. Top—control plant middle—plants grown from seeds with added alkaloids, left—hydroxylupanine, right—lupinine bottom— average leaflets fi om these plants in the same order.

These tetracyclic and tricyclic quinolizidine alkaloids are commonly known as lupine alkaloids. The simple bicyclic alkaloids such as lupinine are produced from two lysine units via cadaverine. Tricyclic alkaloids such as cytisine are considered to be formed from tetracyclic alkaloids through anagyrine-type alkaloids (Fig. 5.2.7). 

The composition of the major alkaloids of different lupine seed species is shown in Table 10.3. The main alkaloids of white lupine seeds are lupanine and albine, of blue lupine seeds lupanine and 13-hydroxylupanine and of yellow lupine seeds lupinine and sparteine. The content of other toxic and antinutritional substances (lectins, trypsin inhibitors and phytates) in lupine seeds is similar to the content of other legume seeds. 

The starting material for the synthesis of the lupin alkaloids is the amino acid lysine, which is first decarboxylated to give its biogenic amine cadaverine. Two units of cadaverine are then joined via a still hypothetical intermediate to give lupinin. Addition of another cadaverine unit to lupinin gives sparteine, which then can be oxidized to lupanin and, further, to hydroxylupanin. The C skeleton of the quinolizidine alkaloids is derived entirely from lysine. We shall now consider two further groups of alkaloids, the nicotiana alkaloids and the tropane alkaloids, which derive only a part of their C skeleton from the aliphatic amino acids ornithine or lysine. 

Not included in the Table are the results of a colossal GC-MS chemotaxonomic survey of the alkaloidal profiles of 56 Lupinus species (embracing 90 subspecies and chemotypes) representing both Old World and New World taxa 337). Of interest in this survey is the finding that bicyclic alkaloids of the lupinine class occurred mainly in Old World species. Genetic evidence has also been obtained for a close relationship between (and probably a common ancestry for) lupines that produce the lupinine complex of metabolites 33S). 

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