Lupin Alkaloids Research Articles

Indolizidine and quinolizidine alkaloids.

This review covers the isolation, structure determination, synthesis and biological activity of indolizidine and quinolizidine alkaloids from microbial, plant and animal sources. Included in the review are slaframine; hydroxylated indolizidines and their analogues; alkaloids from ants and amphibians; metabolites of the genera Prosopis, Streptomyces and Nuphar and the Lythraceae; phenanthroindolizidines and related alkaloids; lupin alkaloids; and alkaloids from sponges. tunicates and coccinellid beetles. The literature from July 2000 to June 2001 is reviewed, and 172 references are cited.

HOST EFFECTS ON HERBIVORY AND POLLINATION IN A HEMIPARASITIC PLANT

The indirect effects of hosts on interactions between parasites and other species are not well understood, and it may be difficult to predict the outcome of host species effects on parasite performance due to the complexity of potential direct and indirect effects. For example, parasitic plants obtain defensive compounds as well as nutrients from their hosts, and thus many attributes of parasitic plants are dependent on the quality of their host species. Here I measure the effect of a lupine host species ( Lupinus argenteus) compared to other host species on herbivory, pollination, and female plant fitness in the hemiparasite Indian paintbrush (Castilleja miniata) using a series of field experiments. Association with lupine was determined in the field by assaying Indian paintbrush leaves for lupine alkaloids. I found that Indian paintbrush plants parasitizing lupines experienced reduced herbivory from plume moth larvae, agromyzid fly larvae, and deer, relative to Indian paintbrush plants parasitizing other host species. However, there was no correlation between alkaloid content of inflorescences and plume moth performance. Host species did not affect pollinator preference for Indian paintbrush in the field. Indian paintbrush para- sitizing lupines produced twice as many seeds overall as Indian paintbrush parasitizing other host species. Correlations suggest that this benefit arises both from reduced herbivory and increased nitrogenous resources. The reduction of herbivory in Indian paintbrush plants parasitizing lupines indicates that host species can affect performance of hemiparasites via indirect pathways, and that the larger community of herbivores could alter the impact of a host on its plant parasites.

ChemInform Abstract: Total Synthesis of the Putative Structure of the Lupin Alkaloid Plumerinine.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Determination of sophoridine and related lupin alkaloids using tris(2,2′-bipyridine)ruthenium electrogenerated chemiluminescence

Electrogenerated chemiluminescences (ECLs) based on tris(2,2′-bipyridine)ruthenium(II) (Ru(bpy) 3 2+) and lupin alkaloids, for instance, sophoridine (SRI), matrine (MT), sophoranol (SR) and sophocarpine (SC) in an aqueous alkaline buffer solution (pH 9.0) are studied. The light emission is mainly caused by an electro-oxidation reaction between tertiary amino group on the alkaloid compounds and Ru(bpy) 3 2+ in a thin layer flow cell equipped with a glassy carbon disc electrode (22.1 mm 2) at the potential of +1.50 V (versus Ag/AgCl). The luminescence wavelength of 610 nm confirmed that ECL is caused by Ru(bpy) 3 2+∗ to its ground state. ECL intensities of these lupin alkaloids are affected by the substituent character, three-dimensional conformation of hydrogen on β-carbon atom. Ionization potentials taken from calculation data further confirm the experimental results. In addition, the factors affecting the determination and HPLC separation of the four alkaloids are also investigated.

Total synthesis of the putative structure of the lupin alkaloid plumerinine.

[reaction: see text]. A stereocontrolled synthesis of quinolizidine 1, the reported structure of plumerinine, has been accomplished in 10 steps from 4-methoxypyridine. The key step is a highly facial selective intramolecular [2 + 2] photocycloaddition of a 2,3-dihydro-4-pyridone. The reported spectral data for plumerinine did not match that of our synthetic 1.

Molecular biological studies on diversity of secondary metabolism in medicinal plants and application to the production in transgenic plants

A molecular biological approach was applied to the study of diversity and regulation of secondary metabolism in medicinal plants at various levels. For the inter-species diversity, RFLP (restriction fragment length polymorphism) and RAPD (random amplified polymorphic DNA) analyses of genomic DNA were performed on the plants, belonging to the same genus or family and containing related compounds. Phylogenetic trees of lupin alkaloid containing plants and other medicinal plants, based on RFLP and/or RAPD profiles, showed the relationship between the diversities in genomes and secondary metabolisms. The chemotypes regarding anthocyanin production in Perilla frutescens var. crispa, were subjected to the study on intra-species diversity. The structural genes and the regulatory genes involved in anthocyanin biosynthesis were isolated and their expression in red and green forms was determined by Northern blot analysis. The expression of all structural genes examined was co-ordinately regulated in form-specific manner and by light illumination. The anthocyanin production was enhanced in transgenic plants over-expressing Myc homologue genes from perilla. These results suggested that a protein complex including bHLH factors might regulate the expression of a series of structural genes. Additionally, cDNAs coding anthocyanin 5-O-glucosyltransferase and anthocyanidin synthase were isolated and characterized using recombinant proteins for the time. In conclusion, it was indicated that the molecular biological techniques are powerful tools for the investigation of diversity and regulation of and for the genetic engineering of secondary metabolism in medicinal plants.

An Efficient Enantioselective Entry to the Piperidino-Quinolizidine Ring System of Lupine Alkaloids by Means of N-Acyliminium Ion Initiated Cyclization Reactions

An efficient methodology for the enantioselective synthesis of the decahydro-1,5-methano-pyrido[1,2-a][1,5]diazocine skeleton found in tricyclic lupine alkaloids is described, starting from 3,5-disubstituted piperidines as chiral building blocks. Alkyne- or vinylsilane-terminated N-acyliminium ion cyclizations performed on appropriate 3,7-diazabicyclo[3.3.1]nonane derivatives allow for the highly stereoselective construction of piperidino-quinolizidine ring systems. A preliminary application of this methodology results in the synthesis of the quinolizidine alkaloid virgilidone.

An Efficient Enantioselective Entry to the Piperidino-Quinolizidine Ring System of Lupine Alkaloids by Means of N-Acyliminium Ion Initiated Cyclization Reactions

An efficient methodology for the enantioselective synthesis of the decahydro-1,5-methano-pyrido[1,2-a][1,5]diazocine skeleton found in tricyclic lupine alkaloids is described, starting from 3,5-disubstituted piperidines as chiral building blocks. Alkyne- or vinylsilane-terminated N-acyliminium ion cyclizations performed on appropriate 3,7-diazabicyclo[3.3.1]nonane derivatives allow for the highly stereoselective construction of piperidino-quinolizidine ring systems. A preliminary application of this methodology results in the synthesis of the quinolizidine alkaloid virgilidone.

ChemInform Abstract: Recent Progress on the Lupine Alkaloids in Leguminous Plants Growing Mainly in Japan

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Bacterial removal of quinolizidine alkaloids from Lupinus albus flours

The bacterial detoxification of bitter lupine seed flours using two bacterial strains, previously shown to catabolize lupanine and to degrade other lupine alkaloids in liquid culture media containing protein, is described. The experimental starting conditions were selected to match the compositions and temperatures that might be expected in an industrial operation. A response surface methodology was used to pinpoint trends in alkaloid removal and to determine the best operating conditions for each strain. Alkaloid removal was modeled and the major constraints were identified. Based on the results obtained, it is suggested that enzymatically active bacterial lysates or purified enzyme complexes may possess a high potential for the detoxification of this material, thus constituting a new potential alternative for the processing of lupine seed material into valuable food ingredients.

Recent progress on the lupine alkaloids in leguminous plants growing mainly in Japan

The existence of the lupine alkaloids in leguminous plants mainly growing in Japan has been thoroughly ascertained, and 106 kinds of lupine alkaloids, including 51 kinds of novel lupine-type alkaloids, have been isolated and characterized from 28 species belonging to the 9 genera of leguminous plants (Table 1). Among them (e.g. Fig. 1-2), a number of unusual types of alkaloids (e.g. Fig. 2) may be regarded as possible metabolites of the lupine alkaloids that coexist in the same plant, such as (+)-kuraramine-type, (-)-mamanine-type (Fig. 3), (-)-tsukushinamine-type (Fig. 5) and (+)-hupeol-type (Fig. 7) alkaloids, or as products of alternative biosynthetic pathway, such as tashiromine-type and (-)-camoensidine-type alkaloids in the Maackia species. The biosynthetic pathways (Fig. 8) by enzymes (Fig. 9) and some of biological activities (e.g. Table 2) of the lupine alkaloids have also been presented. The leguminous plants that accumulate the common lupine alkaloids may be divided into three main groups: plants which produce the matrine, the cytisine/sparteine, and the lupinine-type alkaloids. In addition, the Maackia species and a few other species produce rare bases. Some of more detailed chemical properties of the lupine alkaloids that have been isolated and studied in our laboratory, including a newly proposed biosynthetic pathway, biotechnological studies, a summary of biological activities, and a discussion of chemotaxonomic aspects of the leguminous plants which accumulate lupine alkaloids, have been reviewed by authors in English papers shown in References 1, 55, 65, and also reviewed by one of the authors (I.M.) in a Japanese papers shown in Ref. 66, in which many aspects of the active research history on (+)-matrine and its relatively alkaloids since 1892 in Japan are described.

Lupin alkaloids from Chinese Maackia amurensis.

Two new alkaloids were isolated together with 16 known lupin alkaloids from the leaves and stems of Chinese Maackia amurensis. Their structures were determined by spectroscopic methods to be (-)-6alpha-methoxylupanine and (-)-5alpha-(12-cytisinylmethyl)-6alpha-hydroxylupan ine and identified by comparison with synthetic samples. The structures of lupin alkaloids were also related to the geographical distributions of the Maackia plants.

The hypoglycemic effect of (7R*,9aS*)-7-phenyl-octahydroquinolizin-2-one in mice.

(-)-Multiflorine (1), which was isolated from leguminous plants, produced a hypoglycemic effect when administered to mice with streptozotocin-induced diabetes. (-)-Multiflorine has an enaminone type conjugation on the A-ring, which is unusual in lupine alkaloids. Proceeding on the assumption that the A-B ring is responsible for the activity, several compounds bearing quinolizidin-2-one were synthesized and their hypoglycemic effects were examined. The hypoglycemic effect of (7R*,9aS*)-7-phenyl-octahydroquinolizin-2-one was approximately 4 times stronger than that of (-)-multiflorine measured by oral glucose tolerance test in normal mice. This result indicates that compounds possessing the quinolizidin-2-one ring system as the basic structure may be possible lead compounds for a new type of diabetes drug.

Kappa-Opioid receptor-mediated antinociceptive effects of stereoisomers and derivatives of (+)-matrine in mice.

The antinociceptive effects of seven matrine-type lupin alkaloids were examined using the acetic acid-induced abdominal contraction test (the writhing test) and the tail-flick test in mice. (+)-Allomatrine, the C-6 epimer of (+)-matrine, produced the antinociceptive effect at 1/3 potency of (+)-matrine or pentazocine. It was demonstrated that the antinociceptive effects of (+)-allomatrine were mediated through the activation of kappa-opioid receptors, while the antinociceptive effect of (+)-matrine was mediated by both mu- and kappa-opioid receptors. (-)-Sophoridine, the C-6 epimer of (+)-matrine, (+)-sophoranol, (-)-14 beta-hydroxymatrine and (+)-matrine N-oxide, which possess a hydrophilic group, and (-)-sophocarpine and (-)-sophoramine having a double bond(s) did not show significant antinociceptive activity.

Lupin alkaloids from seeds of Sophora viciifolia

Abstract Three new lupin alkaloids, (−)-14β-hydroxysophoridine, (−)-12β-hydroxysophocarpine and (−)-9α-hydroxysophocarpine, were isolated from the seeds of Sophora viciifolia together with 10 known lupin alkaloids, (+)-9α-hydroxymatrine, (−)-14β-hydroxymatrine, (+)-lupanine, (−)-5,6-dehydrolupanine, (−)-cytisine, (+)-matrine, (+)-matrine N -oxide, (−)-sophocarpine, (+)-sophocarpine N -oxide and (−)-sophoridine.

(-)-14.BETA.-Acetoxymatrine and (+)-14.ALPHA.-Acetoxymatrine, Two New Matrine-Type Lupin Alkaloids from the Leaves of Sophora tonkinensis.

Two new lupin alkaloids, which are the first ester derivatives of matrine-type lupin alkaloids, (-)-14β-acetoxymatrine and (+)-14α-acetoxymatrine, were isolated from the leaves of Sophora tonkinensis along with fourteen known lupin alkaloids: 17-oxo-α-isosparteine, (-)-sophocarpine, (+)-matrine, (-)-14β-hydroxymatrine, (+)-14α-hydroxymatrine, 13,14-dehydrosophoranol (5α-hydroxysophocarpine), (+)-sophoranol, (+)-9α-hydroxymatrine, lamprolobine, (+)-3α,5α-dihydroxymatrine, (-)-baptifoline, (+)-matrine N-oxide, (+)-sophocarpine N-oxide, and (+)-sophoranol N-oxide.

Lupin Alkaloids from Chinese Maackia Hupehensis.

Two new lupin alkaloids, (-)-N-(2-oxopyrrolidinomethyl)cytisine and (-)-N-(N-acetylaminomethyl)cytisine, were isolated together with 9 known alkaloids from Chinese Maackia hupehensis, which grows in the south of China. The alkaloidal constituents of M. hupehensis were shown to be comparable to those of the southern species of Japanese Maackia plants.

Alkaloids of Bongardia chrysogonum

Two new pyridine alkaloids were isolated from the tubers of Bongardia chrysogonum, together with a new lupine alkaloid. The structures of the new alkaloids were characterized by spectroscopic analysis and the stereochemistry was confirmed by applying Horeau's method.

Crystal structure of (−)- Δ16(17)-dehydrolupaninium perchlorate from sealed-tube and synchrotron X-ray diffraction data

Two independent X-ray structure determinations on the same crystal sample of the lupine alkaloid (−)- Δ 16(17)-dehydrolupaninium perchlorate, [C 15H 23N 2O] +·ClO − 4, were carried out, one using a laboratory 4-circle diffractometer equipped with a sealed X-ray tube, and the other, a 6-circle diffractometer installed at the Swiss-Norwegian beam line at the ESRF in Grenoble. The same crystal sample was used but different setting angles for positioning reflections were applied. The measurements provide the most precise dimensions obtained so far for the immonium group. Both determinations reveal consistent details of the dehydrolupaninium cation structure and of ClO − 4 anion distortions. The cation rings A, B, C and D assume distorted half-chair, chair, distorted sofa, and chair conformations, respectively. No short electrostatic interactions between the immonium group and the perchlorate anion are observed, in contrast to all previous studies.

NEW ALKALOIDS FROM LUPINUS ALBUS L. SEEDS

Two new lupin alkaloids, (+)-14-dehydro-10a-hydroxytermisine, (-)-13a-hydroxy-5,6-dehydromultiflorine N-oxide have been isolated from the ethanolic extract of Lupinus albus seeds together with (+)-13a-(2-methylbutyryl)-oxylupanine, (+)-a-isolupanine, (+)-ammodendrine and (-)-sparteine. The structure elucidation of these alkaloids is based on spectroscopic and semisynthetic methods.