Scutellarein 4'-methyl ether glycosides as taxonomic markers in Teucridium and Tripora (Lamiaceae,Ajugoideae)

The flavonoid profiles of two monotypic genera, Teucridium and Tripora, have been studied by analytical methods. These genera were formerly placed in the Verbenaceae, but are now classified in the Lamiaceae, subfamily Ajugoideae. The major flavonoids of both genera were identified as glycosides of scutellarein 4'-methyl ether (5,6,7-trihydroxy-4'methoxyflavone) and acacetin (5,7-dihydroxy-4'-methoxyflavone). The new flavone glycoside, scutellarein 4'-methyl ether 7-O-rutinoside, was isolated from Teucridium parvifolium and the rare scutellarein 4'-methyl ether 7-O-glucuronide from Tripora divaricata. The latter compound has only been reported previously in the related genus Clerodendron. The potential of these flavonoids as taxonomic markers for the tribe Ajugoideae is discussed.     

Anthocyanin 3-galactosides from Cornus alba 'Sibirica' with glucosidation of the B-ring

The three anthocyanins, delphinidin 3-O-beta-galactopyranoside-3',5'-di-O-beta-glucopyranoside (1), delphinidin 3-O-beta-galactopyranoside-3'-O-beta-glucopyranoside (2) and cyanidin 3-O-beta-galactopyranoside-3'-O-beta-glucopyranoside (3), and the 3-O-beta-galactopyranosides of delphinidin (4) and cyanidin (5) were isolated from the bluish white berries and compound umbel of Siberian dogwood, Cornus alba 'Sibirica'. The ornamental autumn leaves and the characteristic purplish red bark of this variety were found to contain only pigment 5.     

Two aurone glycosides from heartwood of Pterocarpus santalinus

Two new aurone glycosides, 6 hydroxy 5 methyl 3',4',5' trimethoxy aurone 4-O-alpha-L-rhamnopyranoside and 6,4' dihydroxy aurone 4-O-rutinoside have been isolated from the ethanolic extract of the wood of Pterocarpus santalinus. Their structures were determined on the basis of chemical and spectroscopic analysis (UV, IR, EIMS, (1)H and (13)C NMR).     

Flavonoid glycosides from Centaurea pseudoscabiosa subsp. pseudoscabiosa from Turkey

Three flavonoid glycosides were isolated and characterized, together with a further 13 substances belonging to various classes of compounds, in particular two phenolic acids, a coumarin, a sugar and nine flavonoids from the flowered aerial parts of Centaurea pseudoscabiosa subsp. pseudoscabiosa Boiss. et Buhse (Asteraceae). Some considerations about their evolutionary meaning are provided.     

Polyoxygenated flavonoids from Eugenia edulis

Leaves of Eugenia edulis contain the new polyoxygenated flavonoid derivatives, gossypetin-3,8-dimethyl ether-5-O-beta-glucoside; gossypetin-3,5-dimethyl ether, and myricetin-3,5,3'-trimethyl ether. In addition, ten known polyphenolics were also isolated and identified. All structures were established on the basis of chemical and spectral evidence, including ESI-MS and 13C NMR.     

Constituents of the stems of Macrococculus pomiferus and their inhibitory activities against cyclooxygenases-1 and -2

As part of our program directed towards the discovery of new cancer chemopreventive agents from plants, the EtOAc-soluble extract of the stems of M. pomiferus was found to inhibit the enzyme cyclooxygenase-2 (COX-2). Bioassay-directed fractionation of this extract led to the isolation of two dibenzylbutyrolactone lignans, (8R,8'R)-3'-O-demethyl-5-hydroxymatairesinol (1) and (8R,8'R)-3'-O-demethyl-5-methoxymatairesinol (2), as well as seven known compounds, (-)-5'-methoxyyatein (3), blumenol A, (-)-deoxypodophyllotoxin (anthricin), (-)-deoxypodorhizone, 2,6-dimethoxyhydroquinone, 4-hydroxybenzaldehyde, and beta-sitosterol glucoside. The structures of compounds 1 and 2 were determined using spectroscopic data (1D and 2D NMR, and HREIMS), and the 8R and 8'R absolute stereochemistry was established for both 1 and 2 on the basis of their CD spectra. All isolates obtained in the present study were evaluated for their inhibitory effects with both COX-1 and -2. Of these, only 5'-methoxyyatein (3) showed weak activity against COX-2, while all other compounds isolated were inactive. The COX-2 inhibitory activity of the EtOAc extract was also traced to the presence of several common fatty acids by LC-MS.     

Chemical constituents of the seeds of Ammopiptanthus (Leguminosae) and their systematic and ecological significance

Eleven flavonoids including a new flavone glycoside, 7,3′-dihydroxy-4′-methoxyflavone-7-O-β-glucopyranoside, and a quinolizidine alkaloid, lupanine, were isolated from the seeds of two Ammopiptanthus (Leguminosae) species, Ammopiptanthus mongolicus and Ammopiptanthus nanus. 7,3′-Dihydroxy-4′-methoxyflavone and lupanine were the major constituents in the seeds of both species. The patterns of seed flavonoids presented a clear systematic relationship between the two species. The simple seed alkaloid composition was presumed to be responsible for the weak defense capability of the seeds to insect pests in both species.     

Six naphthylisoquinoline alkaloids and a related benzopyranone from a Congolese Ancistrocladus species related to Ancistrocladus congolensis

From the roots of a recently discovered Ancistrocladus taxon, with close affinities to Ancistrocladus congolensis regarding molecular ITS sequence data, six naphthylisoquinoline alkaloids, 5'-O-demethylhamatine (2), 5'-O-demethylhamatinine (3), 6-O-demethylancistroealaine A (4), 6,5'-O,O-didemethylancistroealaine A (5), 5-epi-6-O-methylancistrobertsonine A (6), and 5-epi-4'-O-demethylancistrobertsonine C (7), have been isolated, along with a likewise benzopyranone carboxylic acid, 8. The structural elucidation succeeded by chemical, spectroscopic, and chiroptical methods. Their bioactivities were tested against protozoan parasites causing severe tropical diseases. Furthermore, eight known related alkaloids were identified.     

Flavonoid 5-glucosides from the cocoon shell of the silkworm, Bombyx mori

The flavonoid 5-glucosides, quercetin 5,4'-di-O-beta-D-glucopyranoside and quercetin 5,7,4'-tri-O-beta-D-glucopyranoside, together with the known quercetin 5-O-beta-D-glucopyranoside, were isolated from the cocoon shell of the silkworm, Bombyx mori. The structures were identified by spectroscopic analysis. These flavonoid glucosides were not present in mulberry leaves, the silkworm's only food, and they are considered to be metabolites produced by the silkworm.     

Potato tuber isoapyrases: substrate specificity, affinity labeling, and proteolytic susceptibility

Apyrase/ATP-diphosphohydrolase hydrolyzes di- and triphosphorylated nucleosides in the presence of a bivalent ion with sequential release of orthophosphate. We performed studies of substrate specificity on homogeneous isoapyrases from two potato tuber clonal varieties: Desiree (low ATPase/ADPase ratio) and Pimpernel (high ATPase/ADPase ratio) by measuring the kinetic parameters K(m) and k(cat) on deoxyribonucleotides and fluorescent analogues of ATP and ADP. Both isoapyrases showed a broad specificity towards dATP, dGTP, dTTP, dCTP, thio-dATP, fluorescent nucleotides (MANT-; TNP-; ethene-derivatives of ATP and ADP). The hydrolytic activity on the triphosphorylated compounds was always higher for the Pimpernel apyrase. Modifications either on the base or the ribose moieties did not increase K(m) values, suggesting that the introduction of large groups (MANT- and TNP-) in the ribose does not produce steric hindrance on substrate binding. However, the presence of these bulky groups caused, in general, a reduction in k(cat), indicating an important effect on the catalytic step. Substantial differences were observed between potato apyrases and enzymes from various animal tissues, concerning affinity labeling with azido-nucleotides and FSBA (5'-p-fluorosulfonylbenzoyl adenosine). PLP-nucleotide derivatives were unable to produce inactivation of potato apyrase. The lack of sensitivity of both potato enzymes towards these nucleotide analogues rules out the proximity or adequate orientation of sulfhydryl, hydroxyl or amino-groups to the modifying groups. Both apyrases were different in the proteolytic susceptibility towards trypsin, chymotrypsin and Glu-C.     

A rationale for the shift in colour towards blue in transgenic carnation flowers expressing the flavonoid 3',5'-hydroxylase gene

Recently marketed genetically modified violet carnations cv. Moondust and Moonshadow (Dianthus caryophyllus) produce a delphinidin type anthocyanin that native carnations cannot produce and this was achieved by heterologous flavonoid 3',5'-hydroxylase gene expression. Since wild type carnations lack a flavonoid 3',5'-hydroxylase gene, they cannot produce delphinidin, and instead accumulate pelargonidin or cyanidin type anthocyanins, such as pelargonidin or cyanidin 3,5-diglucoside-6"-O-4, 6"'-O-1-cyclic-malyl diester. On the other hand, the anthocyanins in the transgenic flowers were revealed to be delphinidin 3,5-diglucoside-6"-O-4, 6"'-O-1-cyclic-malyl diester (main pigment), delphinidin 3,5-diglucoside-6"-malyl ester, and delphinidin 3,5-diglucoside-6",6"'- dimalyl ester. These are delphinidin derivatives analogous to the natural carnation anthocyanins. This observation indicates that carnation anthocyanin biosynthetic enzymes are versatile enough to modify delphinidin. Additionally, the petals contained flavonol and flavone glycosides. Three of them were identified by spectroscopic methods to be kaempferol 3-(6"'-rhamnosyl-2"'-glucosyl-glucoside), kaempferol 3-(6"'-rhamnosyl-2"'-(6-malyl-glucosyl)-glucoside), and apigenin 6-C-glucosyl-7-O-glucoside-6"'-malyl ester. Among these flavonoids, the apigenin derivative exhibited the strongest co-pigment effect. When two equivalents of the apigenin derivative were added to 1 mM of the main pigment (delphinidin 3,5-diglucoside-6"-O-4,6"'-O-1-cyclic-malyl diester) dissolved in pH 5.0 buffer solution, the lambda(max) shifted to a wavelength 28 nm longer. The vacuolar pH of the Moonshadow flower was estimated to be around 5.5 by measuring the pH of petal. We conclude that the following reasons account for the bluish hue of the transgenic carnation flowers: (1). accumulation of the delphinidin type anthocyanins as a result of flavonoid 3',5'-hydroxylase gene expression, (2). the presence of the flavone derivative strong co-pigment, and (3). an estimated relatively high vacuolar pH of 5.5.     

Neolignan and flavonoid glycosides in Juniperus communis var. depressa

Two neolignan glycosides (junipercomnosides A and B) were isolated from aerial parts of Juniperus communis var. depressa along with two known neolignan glycosides and seven flavonoid glycosides. The structures of the isolated compounds were determined by spectral analysis, in particular by 2D-NMR analysis. The significance of distribution of flavonoids in the chemotaxonomy of genus Juniperus was also discussed.     

Chemotaxonomic relevance of cardenolides in Urginea fugax

In a chemotaxonomic approach the investigation of a methanolic extract of bulbs of Urginea fugax (MORIS) STEINH. resulted in the detection of several cardenolides. The structure of a novel compound, named fugaxin (1), was established as 12alpha,14beta-dihydroxy-2alpha,3beta-(tetrahydro-3',5'-dihydroxy-4'-methoxy-6'-methyl-2H-pyran-2',4'-diylbisoxy)-card-4,20-dienolide by extensive NMR spectroscopic studies including 2D-NMR techniques (COSY, HSQC, HMQC) and selective 1D experiments (NOE, TOCSY) as well as HR-ESI-MS. The chemotaxonomic relevance of the occurrence of cardenolides in the genus Urginea is discussed.     

Anthocyanins in Caprifoliaceae

The qualitative and relative quantitative anthocyanin content of 19 species belonging to the genera Sambucus, Lonicera and Viburnum in the family Caprifoliaceae has been determined. Altogether 12 anthocyanins were identified; the 3-O-glucoside (2), 3-O-galactoside (5), 3-O-(6″-O-arabinosylglucoside) (7), 3-O-(6″-O-rhamnosylglucoside) (9), 3-O-(2″-O-xylosyl-6″-O-rhamnosylglucoside) (10), 3-O-(2″-O-xylosylgalactoside) (11), 3-O-(2″-O-xylosylglucoside) (12), 3-O-(2″-O-xylosylglucoside)-5-O-glucoside (14), 3-O-(2″-O-xylosyl-6″-O-Z-p-coumaroylglucoside)-5-O-glucoside (15) and 3-O-(2″-O-xylosyl-6″-O-E-p-coumaroylglucoside)-5-O-glucoside (16) of cyanidin, in addition to the 3-O-glucosides of pelargonidin and delphinidin (1 and 3). Pigment 7 is the first complete identification of the disaccharide vicianose, 6″-O-α-arabinopyranosyl-β-glucopyranose, linked to an anthocyanidin.     

A hemiterpene glucoside as a probing deterrent of the bean aphid, Megoura crassicauda, from a non-host vetch, Vicia hirsuta

The bean aphid, Megoura crassicauda Mordvilko, feeds selectively on plants belonging to the genus Vicia (Fabaceae). However, it never infests the tiny vetch, V. hirsuta (L.) Gray. The aphid appeared to discriminate between host and non-host plants by tasting specific chemicals during penetration of its stylet into the plant tissues. The aphid, after being stimulated by specific probing stimulants, deposited characteristic proteinous stylet sheaths through a parafilm membrane, which has one side in contact with an extract solution of Vicia angustifolia. However, an addition of a V. hirsuta extract to the medium strongly inhibited the salivary sheath formation. A specific probing deterrent was isolated from a V. hirsuta extract by monitoring the inhibitory effect, and identified as (E)-2-methyl-2-butene-1,4-diol 4-O-beta-d-glucopyranoside. A mixture of the glycoside and the stimulatory V. angustifolia fraction in the same equivalency found in plants significantly decreased the probing activity in M. crassicauda. Since the stylet insertion process is a crucial step for the aphid's settlement on a plant, the glycoside seems to act as an effective chemical barrier for V. hirsuta.     

Guanosine Analogues as Anti-Herpesvirus Agents

Abstract

Several guanosine analogues, i.e. acyclovir (and its oral prodrug valaciclovir), penciclovir (in its oral prodrug form, famciclovir) and ganciclovir, are widely used for the treatment of herpesvirus (i.e. HSV-1, HSV-2, VZV and HCMV) infections. In recent years, several new guanosine analogues have been developed, including the 3-membered (cyclopropyl) sugar derivative A-5021 and the 6-membered D- and L-cyclohexenyl derivatives. Prominent features shared by all guanosine analogues are the following. They depend for their phosphorylation on the virus-encoded thymidine kinase (TK), which makes them particularly effective against those viruses (HSV-1, HSV-2 and VZV) that encoded for such TK. They are also active against HCMV, whether or not they are subject of phosphorylation by the HCMV-induced UL97 protein kinase. Their antiviral activity can be markedly potentiated by mycophenolic acid, an IMP dehydrogenase inhibitor, and they hold great promise, not only as antiviral agents for the treatment of herpesvirus infections, but also as antitumor agents for the combined gene therapy/chemotherapy of cancer, provided that (part of) the tumor cells have been transfected by the viral TK gene.     

Isolation and structure elucidation of 5′-O-β-d-glucopyranosyl-dihydroascorbigen from Cardamine diphylla rhizome

From the methanol extract of Cardamine diphylla rhizome, 5′-O-β-d-glucopyranosyl-dihydroascorbigen (1) and 6-hydroxyindole-3-carboxylic acid 6-O-β-d-glucopyranoside (2) were isolated. The structures of the compounds were elucidated using spectroscopic methods. This is the second report on the presence of a glucosylated indole ascorbigen in plants.     

Cyclohexanoid protoflavanones from the stem-bark and roots of Ongokea gore

Phytochemical investigation of root and stem-bark of the West African medicinal plant Ongokea gore resulted in the isolation of four novel flavonoids with an unusual cyclohexyl substituent instead of the common aromatic ring B. The structures of the isolated compounds were elucidated by spectroscopic methods, mainly 1D and 2D NMR, and subsequently, the structures were corroborated by chemical conversion to (-)-(S)-sakuranetin. The absolute configurations, and preferred conformations were determined by NOE experiments and CD measurements.     

Flavonoids, including an unusual flavonoid-Mg2+ salt, from roots of Cudrania cochinchinensis

Four flavonoids with 2',4'-di-oxygenated B-rings, cochinchinol A (1), cochinchinol B (2), (2R,3R)-4',7-dihydroxy-2',5-dimethoxydihydroflavonol (3), 4',7-dihydroxy-2',5-dimethoxyflavonol (4), along with 11 known compounds, were isolated from an ethanolic extract of the roots of Cudrania cochinchinensis. Their structures were elucidated by chemical and spectroscopic methods. Cochinchinol A (1) and cochinchinol B (2) have two hitherto unprecedented flavonol salt structures in natural product chemistry. Cytotoxic activities were evaluated against several different cell lines.