Of lupine alkaloids

In the course of biogenesis-type syntheses of lupin alkaloids, reduction of protected macrocyclic acyloin 50 (Scheme 15) has been found to be a second route to bicyclic aminoalcohol 14a (69JA7372). Another 11-membered ring compound, namely caprinolactam (51), on anodic oxidation in the presence of halide ions produces 6/7 bicyclic lactam 52 together with two isomeric 5/8 bicyclic lactams (87CJC2770). 

Aniszewski, T. 1994. From iodine to enzyme A critical review of chemical and biological methods of lupine alkaloids analysis. Science of Legumes, 1 25-36. 

Golebiewski, W. M. and Spenser, I. D. 1976. The biosynthesis of lupine alkaloids. A reexamination. Journal of American Chemical Society, 21 6726-6728. 

Korcz, A., Markiewicz, M., Pulikowska, J., and Twardowski, T. 1987. Species-specific inhibitory effects of lupine alkaloids on translation in plants. J. Plant Physiol. 128, 433-442... 

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. 

During 1993, Daly and co-workers reviewed the alkaloids found in amphibians [5] and Takahata et al. focused on structural assignments and the synthesis of amphibian and polyhydroxylated indolizidines [6]. Wink reviewed the characterisation, natural distribution and biological activity of lupine alkaloids [7] and systematic updates on indolizidine and quinolizidine alkaloids are annually summarized by Michael [8-14]. 

The mass spectra of a number of lupine alkaloids have been determined and their interpretation has been confirmed by deuteration (7). 

Gas chromatographic separation and isolation of microgram amounts of lupine alkaloids combined with mass spectrometry was used by Cho and Martin for the unambiguous identification of 20 such alkaloids. The retention times on a packed column of 10 % QF-1 and the five most abundant ions by spectrometry are listed in Table 7.4. 

EXPERIMENTAL CONDITIONS USED FOR GAS CHROMATOGRAPHY OF LUPINE ALKALOIDS... 

Simple bicyclic compounds form a rather small subset of the lupine (or lupin) alkaloids, the overwhelming majority of which have tricyclic or tetracyclic structures based on the quinolizidine motif. These alkaloids are characteristic metabolites of the Papilionoideae, a sub-family of the Leguminosae (Fabaceae), although representative examples have also been isolated from several other plant families. The simple lupine quinolizidines were surveyed in Volume 28 of this treatise (7), while later reviews in Volumes 31 (5) and 47 (9) comprehensively covered all classes of lupine alkaloids, including those containing indolizidine components. Much relevant material is also to be found in the review on the biosynthesis of pyrrolizidine and... 

A new alkaloid of Sarothamnus scoparius seems to be the same dehydrosparteine obtained in transformation of lupin alkaloids by plant cell cultures and regarded as 11,12-dehydrosparteine (10)... 

The formation of lupin alkaloids in the early days of growth seems, on the other hand, to be promoted by light, even though the assay falls on account of the more rapid simultaneous formation of carbohydrate. Thus Sabalitschka and Jungermann (39) recorded 86.2 mg. alkaloid in 2-week-old... 

Chemistry, Biochemistry and Chemotaxonomy of Lupine Alkaloids in the Leguminosae... 

Numerous original research articles have been published on various aspects of the chemistry and biochemistry of lupin alkaloids. Some excellent reviews and chapters in books have attempted to provide comprehensive lists of known lupin alkaloids [2-6]. Recent advances, specially on the chemistry of these alkaloids, have appeared in the annual reviews published by the Royal Society of Chemistry [7]. Therefore, in this chapter we summarize the natural occurrence and structural characteristics of newly discovered alkaloids in our recent investigations with brief comments on the spectroscopy of the alkaloids. We also describe the summarized results of biochemical aspects including plant tissue culture and works on isolated enzymes. Chemotaxonomic and pharmacological significance of the alkaloids will be given briefly. 

Matrine (7) (+)-Ammodendrine (8) (-)-Tsukushinamine-A (9) Fig. 1 Types of structure of lupin alkaloids in Leguminous plants... 

Since, in the H-NNIR spectra of lupin alkaloids, most signals of alicyclic hydrogens appear in the range of S 1-2.5, it is not easy to assign all overlapping signals. However, several characteristic features in the spectra are helpful for structural elucidation. In the IH-NMR spectra of lupanine-type alkaloids, only the signal of Hjoa... 

In most cases, the molecular ions of lupin alkaloids are detectable in electron impact (El) ionization technique, and, therefore, useful for determination of molecular mass and composition by the combination with high resolution mass spectrometry. However, N-oxides usually exhibit very small molecular ion peaks in the El mode. Inbeam ionization technique provides relatively strong molecular ions of the alkaloid N-oxides. However, fast atom bombardment (FAB) mass spectrometry has been recently proved very useful for the determination of the molecular masses of N-oxides. 

In the IR spectra of lupin alkaloids, Bohlmann bands are characteristic for molecules having ra -quinolizidine rings and are useful for structural elucidation. The UV spectra of a-pyridone and multiflorine-type alkaloids show absorptions at... 

The CD spectra provide information about the absolute stereochemistry of these alkaloids. The signs of Cotton effects due to the chirality of structurally similar chromophore predicts the absolute configuration of the alkaloids by comparison to that of known compounds. For the quantification of each known alkaloid in the plant materials, the most reliable data are obtained by the combination of normal-phase HPLC, reverse-phase HPLC and capillary GC/MS. The N-oxides of lupin alkaloid can be normally detected by HPLC. 

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]. 

Table IV The distribution of lupin alkaloids in plants of the Leguminosae.

Some pharmacological activities of lupin alkaloids were briefly summarized by Kinghorn and Balandrin [3]. Recently, some additional interesting activities have been revealed by our study (Table V). 

Table V Example of recently examined biological activities of lupin alkaloids.

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... 

Stereochemistry, syntheses, and biological activity of lupine alkaloids 07YZ1557. 

Wink, M. 1994. Biological activities and potential application of lupin alkaloids. In Neves-Martins, J.M., and M.L. Beirao da Costa, eds. Advances in lupin research. Lisboa ISA Press. 

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