Lupine Lupinine

Bicyclic QAs, such as lupinine and derivatives, already occur in the more ancestral tribes such as Thermopsideae and Podalyrieae. They are rarely found in members of the Cytisus/Genista complex, but are typical for lupins of the subgroup, Scabrispermae (L. atlanticus, L. digitatus, L. princei, L. pi-losus, L. cosentinii), and of the closely related L. luteus/L. hispanicus pair. In North American lupins, bicyclic QAs occur only sporadically as minor components. 

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. 

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). 

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. 

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]. 

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. 

Lupinine (II), isolated from yellow lupin seeds by Cassola (112) in 1835, was obtained in pure form by Baumert in 1881. Derivatives... 

The compound of oxidation state intermediate between that of lupinine and lupininic acid, namely, lupinal, C10H17NO, m.p. 93-96°, has been obtained by Zaboev (72) through the use of chromic anhydride in acetic acid. It appears that the first use of natural lupinine itself as a synthetic tool dates from the work of Bartholomaus and Schaumann, described in two patents (150, 151). Products were characterized which resulted from the condensation of chloro- or bromo-lupinane (derived from lupinine (124, 125)) with ammonia, aniline, methylamine, dimethyl-amine, and piperidine (150). The product resulting from chlorolupinane and piperidine was also described by Clemo and Paper (126). Compounds of possible therapeutic interest were made by the condensation of a halolupinane with 8-amino-2-methylquinoline, 4-amino-2-methyl-quinoline, and by the combination of methylaminolupinane with 4-chloro-... 

Lupins produce both tetracyclic (e.g., lupanine) and bicyclic quinolizidine alkaloids (i.e., lupinine), which typically accumulate as esters of tiglic acid, p-coumaric... 

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