Ipvelutine, 7ß-Acetoxy-2α-(tigloyloxy)tropane, an Unusual Tropane Alkaloid from Ipomoea velutina R. Br. (Convolvulaceae).

Convolvulaceae provide a rich source of tropane alkaloids, however, 2-substituted tropanes have been described for only few species of this taxon. In this note, 2,7-diesters such as ipvelutine [7ß-acetoxy-2α-(tigloyloxy)tropane] isolated from the vegetative parts of the Australian Ipomoea velutina R. BR. are described as a new group of tropane diesters.

Stereochemistry of Consabatine from Convolvulus sabatius Viv. (Convolvulaceae).

The stereochemistry of consabatine, which was isolated from the roots of Convolvulus sabatius Viv. as a novel natural compound, has now been determined by the synthesis of its Mosher esters. Consabatine was found to be 1'R-configurated.

Evolution of homospermidine synthase in the convolvulaceae: a story of gene duplication, gene loss, and periods of various selection pressures.

Homospermidine synthase (HSS), the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, is known to have its origin in the duplication of a gene encoding deoxyhypusine synthase. To study the processes that followed this gene duplication event and gave rise to HSS, we identified sequences encoding HSS and deoxyhypusine synthase from various species of the Convolvulaceae. We show that HSS evolved only once in this lineage. This duplication event was followed by several losses of a functional gene copy attributable to gene loss or pseudogenization. Statistical analyses of sequence data suggest that, in those lineages in which the gene copy was successfully recruited as HSS, the gene duplication event was followed by phases of various selection pressures, including purifying selection, relaxed functional constraints, and possibly positive Darwinian selection. Site-specific mutagenesis experiments have confirmed that the substitution of sites predicted to be under positive Darwinian selection is sufficient to convert a deoxyhypusine synthase into a HSS. In addition, analyses of transcript levels have shown that HSS and deoxyhypusine synthase have also diverged with respect to their regulation. The impact of protein-protein interaction on the evolution of HSS is discussed with respect to current models of enzyme evolution.

Bonabiline A, a monoterpenoid 3alpha-acyloxytropane from the roots of Bonamia spectabilis showing M3 receptor antagonist activity.

Two 3alpha-acyloxytropanes with unique monoterpenoic acyl moieties, bonabiline A and its anhydro derivative bonabiline B, have been isolated from the roots of Bonamia spectabilis. Their structures were elucidated by detailed spectroscopic analysis. Due to the structural similarity of bonabiline A to atropine/hyoscyamine, the affinity of both bonabilines to the muscarinic M (3) receptor was studied in the isolated guinea-pig ileum. Bonabiline A (pA (2) 6.65 +/- 0.03) proved to be a more potent antagonist than bonabiline B (pA (2) 5.50 +/- 0.03).

Chemotaxonomy of the pantropical genus Merremia (Convolvulaceae) based on the distribution of tropane alkaloids.

The occurrence and distribution of tropane and biogenetically related pyrrolidine alkaloids in 18 Merremia species of paleo-, neo-, and pantropical occurrence have been studied. The extensive GC-MS study included members of almost all sections of the genus and has been carried out with epigeal vegetative parts as well as with roots. It comprises altogether 74 tropanes and 13 pyrrolidines including nicotine. Along with datumetine known already from a solanaceous species, the study led to the isolation (from M. dissecta and M. guerichii, respectively) and structure elucidation (spectral data) of four novel 3alpha-acyloxytropanes, merresectines A-D: 3alpha-(4-methoxybenzoyloxy)nortropane (A), 3alpha-kurameroyloxytropane (B), 3alpha-nervogenoyloxytropane (C), 3alpha-[4-(beta-D-glucopyranosyloxy)-3-methoxy-5-(3-methyl-2-butenyl)benzoyloxy]tropane (beta-d-glucoside of D). Moreover, the novel 3alpha,6beta-di-(4-methoxybenzoyloxy)tropane (merredissine) has been isolated from M. dissecta and structurally elucidated. In addition the structures of datumetine and merresectine A could be confirmed by synthesis. Spectral data for two known 3alpha-acyloxytropanes (merresectine E beta-D-glucoside, 4'-dihydroconsabatine) and one known 3beta-acyloxytropane (concneorine) are documented for the first time. The structures of three further merresectines (F-H) have been determined by mass spectrometry. Furthermore, the linkage (2',3- and 2',4-, respectively) of two position isomer N-methylpyrrolidinylhygrines was proven by synthesis. The results of the study contribute to the solution of infrageneric taxonomic problems. Whereas all species yield pyrrolidine alkaloids without suitably differentiating results the diverging occurrence of tropane alkaloids leads to three groups of sections: (1) taxa free of tropanes, (2) taxa with simple tropanes, and (3) taxa with merresectines in addition to simple tropanes.

Calystegines as chemotaxonomic markers in the Convolvulaceae.

An extended GC-MS study of 129 convolvulaceous species belonging to 29 genera (all 12 tribes) including the results of a previous survey (65 spp.) revealed the occurrence of one to six polyhydroxy alkaloids of the nortropane type (calystegines) in 62 species belonging to 22 genera of all tribes except the unique parasitic Cuscuteae. The large genus Ipomoea turned out to comprise calystegine-positive species in at least eight out of ten sections checked. The number of the calystegines used as reference compounds has been increased from seven (previous survey) to 11 (present study). Furthermore, the results concerning these additional four alkaloids could also be completed for all species of the previous survey. The plant material (epigeal vegetative parts and/or roots, flowers, fruits/seeds) was obtained from collections in the wild from a wide range of tropical, subtropical, and temperate locations of all continents as well as from cultivation in the greenhouse. All plant organs turned out to be potential locations for the occurrence of these metabolites though they are detectable often only in certain organs of a given species. Three genera (Cuscuta, Operculina, Polymeria) might have lost the ability to synthesize these plesiomorphic characters in the course of the evolution since the examination of several different organs and/or provenances of five species each failed to show calystegines as constituents. Nevertheless, the present data clearly demonstrate that the occurrence of calystegines is an almost consistent trait in the Convolvulaceae in principle, from basal to most advanced tribes.

Ipangulines and minalobines, chemotaxonomic markers of the infrageneric Ipomoea taxon subgenus Quamoclit, section Mina.

A comprehensive GC-MS analysis of 8 Ipomoea species belonging to the subgenus Quamoclit, section Mina revealed that the members of this taxon form combinations of two necine bases with rare necic acids resulting in unique pyrrolizidine alkaloids. The occurrence and diversity of these metabolites show remarkable variations: Some species, especially Ipomoea hederifolia and Ipomoea lobata, are able to synthesize a large number of alkaloids whereas others, especially Ipomoea coccinea and Ipomoea quamoclit, are poor synthesizers with only a few compounds. However, these metabolites are apparently chemotaxonomic markers of this infrageneric taxon in general. They represent either esters of (-)-platynecine (altogether 48 ipangulines and 4 further esters including results of a previous study) or esters of (-)-trachelanthamidine, an additional novel structural type called minalobines (altogether 21 alkaloids). Both types are characterized by section-specific rare necic acids, e.g., ipangulinic/isoipangulinic acid, phenylacetic acid. The alkaloids of Ipomoea cholulensis, I. coccinea, I. hederifolia, Ipomoea neei, and Ipomoea quamoclit were mono and diesters of platynecine. Minalobines turned out to be metabolites of I. lobata (Cerv.) Thell. (syn.: Mina lobata Cerv.) lacking ipangulines. The major alkaloid of this species, minalobine R, has been isolated and identified as 9-O-(threo-2-hydroxy-2-methyl-3-phenylacetoxy-butyryl)-(-)-trachelanthamidine on the basis of spectral data. Apparently only two of the species included in this study, Ipomoea cristulata and Ipomoea sloteri, are able to synthesize both, ipangulines as well as minalobines. Minalobine O could be isolated as a major alkaloid of I. cristulata, its structure has been established as 9-O-(erythro-2-hydroxy-2-methyl-3-tigloyloxy-butyryl)-(-)-trachelanthamidine on the basis of spectral data.

In vitro antiplasmodial activities of semisynthetic N,N'-spacer-linked oligomeric ergolines.

Starting from three monomeric ergolines (terguride 1, festuclavine 2, pergolide 3) N,N'-spacer-linked oligomeric derivatives were prepared using different aliphatic or arylalkyl spacers. The compounds have been evaluated for their in vitro antiplasmodial activity against the chloroquine-sensitive strain poW and the chloroquine-resistant clone Dd2 of Plasmodium falciparum. Additionally, the cytotoxic effects against mouse fibroblasts (NIH 3T3) in vitro, and human hepatocytes were evaluated. All monomers displayed only a weak antiplasmodial effect, but N-1,N-1'-spacer-linked dimerization substantially enhanced their antiplasmodial activity. The best activities were observed for compounds showing a distance of six carbon atoms between two monomers, which can be obtained by aliphatic or p-xylene linkers. The N-6,N-6'-spacer-linked depropylpergolide dimer 3i exhibited the highest antiplasmodial activity of all compounds tested (IC(50) values: 0.14 and 0.13 microM against poW and Dd2, respectively). Unfortunately, it displayed toxic effects against the mouse fibroblast cell line NIH 3T3 (IC(50): 0.1+/-0.09 microM) and also against human hepatocytes at 100 microM (LDH-leakage: 15.58+/-0.87 microkat/L; GSH-level: 8.15+/-0.78 nmol/10(6) cells). However, the N-1,N-1'-spacer-linked trimer of festuclavine (2f), and also the N-1,N-1'-spacer-linked tetramer of terguride (1g) possessed remarkable antiplasmodial activities (IC(50): 0.54 and 1.53 microM, respectively, against Dd2) lacking cytotoxicity.

Ipobscurines C and D: macrolactam-type indole alkaloids from the seeds of Ipomoea obscura.

Separation of the methanolic seed extract of Ipomoea obscura afforded five indole alkaloids, three of them (ipobscurines B-D) being new natural products of a unique structural type characterized as serotonin hydroxycinnamic acid amide-type conjugates with a second phenylpropanoid moiety forming an ether with the 5-OH position of the indole nucleus. Due to an oxidative phenolic coupling between the two phenylpropanoid moieties of the supposed precursor ipobscurine B two 21-membered macrolactams with a phenol ether partial structure are formed: the trans-cis isomers ipobscurines C and D. Their structures were established on the basis of spectral data. Moreover, total synthesis of the racemic erythro- and threo-ipobscurine B 4',4"-dimethyl ethers and the comparison with the corresponding derivative of natural (-)-ipobscurine B proved an erythro configuration of the latter.

In vitro antiplasmodial evaluation of medicinal plants from Zimbabwe.

In this study the in vitro antiplasmodial activities of extracts from Cussonia spicata (Araliaceae), Artemisia afra, Vernonia colorata, V. natalensis (Asteraceae), Parinari curatellifolia (Chrysobalanaceae), Clutia hirsuta, Flueggea virosa, (Euphorbiaceae), Adenia gummifera (Passifloraceae) and Hymenodictyon floribundum, (Rubiaceae) were evaluated. The lipophilic extracts from the aerial parts of Artemisia afra and Vernonia colorata proved to be the most active against the chloroquine-sensitive strain PoW and against the chloroquine-resistant clone Dd2 of Plasmodium falciparum. Bioassay-guided fractionation of the extract of A. afra yielded seven flavonoids, from which acacetin, genkwanin and 7-methoxyacacetin showed in vitro activity; the IC(50) values ranged from 4.3 microgram/mL to 12.6 microgram/mL. In addition, several sesquiterpene lactones could be obtained from the most active fractions. Whereas eudesmaafraglaucolide proved to be inactive, the guaianolides 1-desoxy-1alpha-peroxy-rupicolin A-8-O-acetate, 1alpha,4alpha-dihydroxybishopsolicepolide and rupicolin A-8-O-acetate revealed in vitro antiplasmodial activity. Evaluation of V. colorata gained four sesquiterpenes 11beta,13-dihydrovernodalin, vernodalol, 11beta,13-dihydrovernolide and 11beta,13,17,18-tetrahydrovernolide, from which the first two constituents exhibited the strongest antiplasmodial activity (IC(50) values: 1.1-4.8 microgram/mL).

Andirol A and B, two unique 6-hydroxymethylpterocarpenes from Andira inermis.

From a methanolic extract of the leaves of Andira inermis (Fabaceae), andirol A and B, two compounds with a novel type of a rotenoid-related skeleton and andinermol, a new 2-aryl-3-hydroxymethyl-benzofuran could be isolated. Characterisation and structure elucidation of these compounds was achieved on the basis of their spectral data. In addition, the in vitro activities of the isolated compounds against both the chloroquine-sensitive strain PoW and the chloroquine-resistant clone Dd2 of Plasmodium falciparum have been evaluated.

In vitro antiplasmodial investigation of medicinal plants from El Salvador.

In vitro antiplasmodial activities of extracts from Albizia saman, Fabaceae, Calea tenuifolia (C. zacatechichi), Asteraceae, Hymenaea courbaril, Fabaceae, Jatropha curcas, Euphorbiaceae, Momordica charantia, Cucurbitaceae, and Moringa oleifera, Moringaceae were evaluated. From the lipophilic extract of C tenuifolia five active flavones were obtained. 4',5-Dihydroxy-7-methoxyflavone [genkwanin] and 5-hydroxy-4',7-dimethoxyflavone [apigenin 4',7-dimethylether] exhibited the strongest antiplasmodial activity against a chloroquine-sensitive strain (poW) and a chloroquine-resistant strain (Dd2) of Plasmodium falciparum [IC50 values: 17.1-28.5 microM). Furthermore octadeca-9,12-dienoic acid [linoleic acid] [IC50] values of 21.8 microM (poW) and 31.1 microM (Dd2)] and octadeca-9,12,15-trienoic acid (alpha-linolenic acid) were isolated.

Antiplasmodial activity of sesquilignans and sesquineolignans from Bonamia spectabilis.

Phytochemical re-investigation of the aerial parts of Bonamia spectabilis (Convolvulaceae) led to the isolation of four minor tetrahydrofuran-type sesquilignans (bonaspectins E-H) together with the known neolignan virolongin A and the known lignan rel-(7S,8R,7'R,8'R)-3,3',4,4',5,5'-hexamethoxylignan. Their structures were established on the basis of spectral data. These six compounds as well as further seven lignanoids from B. spectabilis, characterised previously, were tested for their antiplasmodial activity against a chloroquine-sensitive strain (PoW) and a chloroquine-resistant clone (Dd2) of Plasmodium falciparum. Bonaspectin C 4"-O-glucoside, its aglycone, and bonaspectin D 4"-O-glucoside revealed the highest antiplasmodial activities (IC50 values: 1.3, 2.0, 6.5 microM [PoW]; 1.7, 4.6, 3.7 microM [Dd2], respectively).

Antiplasmodial activity of naphthoquinones and one anthraquinone from Stereospermum kunthianum.

A lipophilic extract of the root bark of Stereospermum kunthianum revealed antiplasmodial activity in vitro. Bioassay-guided fractionation led to the isolation of four novel naphthoquinones (sterekunthals A and B, pyranokunthones A and B) and one novel anthraquinone (anthrakunthone) together with the known naphthoquinone pinnatal. The structures of the novel compounds were determined by comprehensive analyses of their 1D and 2D NMR data. The antiplasmodial activities and toxicity against the endothelial cell line ECV-304 of the isolated compounds have been assessed.

Herbal remedies traditionally used against malaria in Ghana: bioassay-guided fractionation of Microglossa pyrifolia (Asteraceae).

Different extracts from 11 West African plants traditionally used against malaria in Ghana were tested against both the chloroquine-sensitive strain PoW and the chloroquine-resistant clone Dd2 of Plasmodium falciparum. Due to the promising in vitro activity of the lipophilic extract [IC50: 10.5 microg/ml (PoW); 13.1 microg/ml (Dd2)], Microglossa pyrifolia (Lam.) Kuntze (Asteraceae) was chosen for further phytochemical investigation. From active fractions 13 compounds were isolated; their structures were established on the basis of spectroscopic methods. 1-Acetyl-6E-geranylgeraniol-19-oic acid and sinapyl diangelate represent new natural compounds. The two diterpenes E-phytol [IC50: 8.5 microM (PoW); 11.5 microM (Dd2)], and 6E-geranylgeraniol-19-oic acid [IC50: 12.9 microM (PoW); 15.6 microM (Dd2)] proved to be the most active constituents in our test system.