Lanceocrepidiasides A-F, glucosides of guaiane-type sesquiterpene from Crepidiastrum lanceolatum

From the aerial parts of Crepidiastrum lanceolatum, six guaiane-type sesquiterpene glucosides, lanceocripidiasides A-F were isolated together with five known sesquiterpene glucosides, ixerin Y, crepidialanceosides A and B, and youngiasides A and D, two known megastigmane glucosides, icariside B1 and corchoionoside A, and benzyl 6'-O-beta-D-apiofuranosyl-beta-D-glucopyranoside. Structures were elucidated by spectroscopic analyses.     

Lasianthionosides A-C, megastigmane glucosides from leaves of Lasianthus fordii

From the leaves of Lasianthus fordii, three megastigmane glucosides, lasianthionosides A, B and C, were isolated together with the known iridoid glucoside, asperuloside, deacetylasperuloside and methyl deacetyl-asperulosidate, and a megastigmane glucoside, citroside A. The structures have been elucidated based on spectroscopic analyses and/or X-ray crystallographic analysis.     

Crotonionosides A-G: megastigmane glycosides from leaves of Croton cascarilloides Räuschel

From the 1-BuOH-soluble fraction of a MeOH extract of leaves of Crotoncascarilloides, collected in Okinawa, Japan, seven megastigmane glycosides, named crotonionosides A-G, were isolated together with three known megastigmane glucosides, dendranthemosides A and B, and citroside A. This structures were elucidated by a combination of spectroscopic analyses, HPLC analyses, and application of the modified Mosher’s method.     

Euodionosides A-G: megastigmane glucosides from leaves of Euodia meliaefolia

From a 1-BuOH-soluble fraction of the MeOH extract of leaves of Euodia meliaefolia, collected in Okinawa, seven megastigmane glucosides, named euodionosides A-G, were isolated together with three known megastgmane glucosides, and two aliphatic and three phenolic compounds. Their structures were elucidated through a combination of spectroscopic analyses and application of the modified Mosher's method.     

Stereochemistry of megastigmane glucosides from Glochidion zeylanicum and Alangium premnifolium

From Glochidion zeylanicum, two megastigmane glucosides, 3- and 9-O-beta-D-glucopyranosides of (3S,5R,6R,7E,9S)-megastigman-7-ene-3,5,6,9-tetrol (1 and 2, respectively), were isolated. Their structures were different from those of kiwiionoside (3) and actinidioionoside (4), isolated from Actinidia chinensis and Actinidia polygama, respectively, in the stereochemistry at the 9-positions. Alangionosides E (5) and O (6), isolated from the leaves of Alangium premnifolium, are also megastigmane glucosides, and the latter is closely related to 1 and actinidioionoside (4). However, the absolute configurations of the 9-position remained to be determined. They were analyzed to be R by means of a modified Mosher's method. Alangionoside E (5) is identical with corchoionoside A in all aspects. The name of corchoionoside A must be retained thereafter.     

Eudesmane and megastigmane glucosides from Laggera alata

Four eudesmane glucosides, alatosides A-D (1-4), and one megastigmane glucoside, alatoside E (5), were isolated from the BuOH fraction of Laggera alata along with six known compounds. Structures of the new compounds were elucidated by a combination of chemical and spectroscopic methods. Alatosides A-E were characterized as: 1alpha-O-(beta-D-glucopyranosyloxyl)-7-epi-eudesma-11-en-2beta,4alpha-diol (1), 2beta-O-(beta-D-glucopyranosyloxyl)-eudesma-4alpha-hydroxyl-11(13)-en-12-oic-acid (2), 5beta-O-(beta-D-glucopyranosyloxyl)-eudesma-4(15),11(13)-dien-12-oic-acid (3), 5alpha-O-(beta-D-glucopyranosyloxyl)-eudesma-3,11(13)-dien-12-oic acid (4) and 3beta-O-(beta-D-glucopyranosyloxyl)-megastigma-9-one (5), respectively. Based on the chemical characteristics of eudesmane derivatives isolated from the Laggera genus, it was suggested that there are probably two different biogenetic pathways for these secondary metabolites in this genus.     

Diversification of an ancient theme: hydroxynitrile glucosides

Many plants produce cyanogenic glucosides as part of their chemical defense. They are alpha-hydroxynitrile glucosides, which release toxic hydrogen cyanide (HCN) upon cleavage by endogenous plant beta-glucosidases. In addition to cyanogenic glucosides, several plant species produce beta- and gamma-hydroxynitrile glucosides. These do not release HCN upon hydrolysis by beta-glucosidases and little is known about their biosynthesis and biological significance. We have isolated three beta-hydroxynitrile glucosides, namely (2Z)-2-(beta-D-glucopyranosyloxy)but-2-enenitrile and (2R,3R)- and (2R,3S)-2-methyl-3-(beta-D-glucopyranosyloxy)butanenitrile, from leaves of Ribesuva-crispa. These compounds have not been identified previously. We show that in several species of the genera Ribes, Rhodiola and Lotus, these beta-hydroxynitrile glucosides co-occur with the L-isoleucine-derived hydroxynitrile glucosides, lotaustralin (alpha-hydroxynitrile glucoside), rhodiocyanosides A (gamma-hydroxynitrile glucoside) and D (beta-hydroxynitrile glucoside) and in some cases with sarmentosin (a hydroxylated rhodiocyanoside A). Radiolabelling experiments demonstrated that the hydroxynitrile glucosides in R. uva-crispa and Hordeum vulgare are derived from L-isoleucine and L-leucine, respectively. Metabolite profiling of the natural variation in the content of cyanogenic glucosides and beta- and gamma-hydroxynitrile glucosides in wild accessions of Lotus japonicus in combination with genetic crosses and analyses of the metabolite profile of the F2 population provided evidence that a single recessive genetic trait is most likely responsible for the presence or absence of beta- and gamma-hydroxynitrile glucosides in L. japonicus. Our findings strongly support the notion that the beta- and gamma-hydroxynitrile glucosides are produced by diversification of the cyanogenic glucoside biosynthetic pathway at the level of the nitrile intermediate.     

Absolute configuration of (+)-pinoresinol 4-O-[6″-O-galloyl]-β-d-glucopyranoside, macarangiosides E, and F isolated from the leaves of Macarangatanarius

A lignan glucoside, (+)-pinoresinol 4-O-[6″-O-galloyl]-β-d-glucopyranoside (1), and two megastigmane glucosides, named macarangiosides E and F (2,3), together with 15 known compounds (4-18) were isolated from leaves of Macarangatanarius (L.) Müll.-Arg. (Euphorbiaceae). Their structures were elucidated by spectroscopic and chemical analyses. In addition, the absolute stereochemistry of macarangiosides B and C isolated previously from the same plant was also determined for the first time. Compounds 1 and 2 were galloylated on glucose and possessed potent DPPH radical-scavenging activity.     

Iridoid glucosides from Kickxia abhaica D.A. Sutton from Scrophulariaceae

Two iridoid glucosides namely; 6-acetylantirrinoside (1), 6'-O-p-hydroxybenzoylantirrinoside (2) were isolated from the aerial parts of Kickxia abhaica. Beside that, three known iridoid glucosides, antirrinoside (3), antirride (4) and mussaenosidic acid (5), one flavone glycoside (6) and a hexitol, d-mannitol (7) were isolated. The structures of the iridoid glucosides 1-2 were established by 1D and 2D NMR spectral data, including COSY, HMQC and HMBC experiments, as well as HRMS.     

The first cyclomegastigmane rhododendroside A from Rhododendron brachycarpum alleviates HMGB1-induced sepsis

Background

Endangered plant species are a vital resource for exploring novel drug prototypes. A Korean endangered plant Rhododendron brachycarpum G. Don is a broad-leaved shrub native to northern Korea and central Japan. The high mobility group box 1 protein (HMGB1) could be a specific target for the discovery of novel antiseptic agents.

Methods

Gauge-invariant atomic orbital (GIAO) NMR chemical shift calculations were applied for investigation of stereochemical details with accuracy improved by application of DP4 analysis. In vitro antiseptic mechanisms were investigated utilizing immunofluorescence staining, ELISA and cell–cell adhesion assay. Cecal ligation and puncture (CLP) operation was employed to evaluate in vivo potential alleviating severe sepsis and septic shock.

Results

The first bicyclic megastigmane glucoside rhododendroside A (1) along with known megastigmane glucosides (2–5) were isolated from the leaves of R. brachycarpum. The structure of 1 was established by NMR analysis as well as comparison of the experimental chemical shifts with those of computed values employing DP4 application. In the CLP operation model that simulates severe sepsis, rhododendroside A (1) improved the survival rate up to 60%.

Conclusions

Our results exhibit that R. brachycarpum may produce a unique scaffold that is developed into a drug lead mitigating HMGB1-induced vascular pro-inflammatory stimuli and thus alleviating severe sepsis and related manifestations.

General significance

Discovery of new drug leads would warrant conservation efforts of endangered species.     

Quassinoid glucosides from seeds of Brucea amarissima

Quassinoid glucosides, javanicosides I, J, K and L, were isolated from the seeds of Brucea amarissima (Lour.) Desv. ex B. A. Gomes (Simaroubaceae), along with two known quassinoids, i.e. bruceins D and E, and seven known quassinoid glucosides, yadanziosides B, C, E, I and K, bruceoside B and yadanzigan. Their structures were elucidated by analysis of the spectral data and chemical evidence.     

Megastigmane and iridoid glucosides from Clerodendrum inerme

From the aerial parts of Clerodendrum inerme, two megastigmane glucosides (sammangaosides A and B) and a iridoid glucoside (sammangaoside C) were isolated together with 15 known compounds. The structural elucidations were based on analyses of physical and spectroscopic data.     

Chemotaxonomic markers in Digitalideae (Plantaginaceae)

In a chemosystematic investigation of Digitalideae (Plantaginaceae), the water-soluble part of extracts of two species of Digitalis, two species of Isoplexis, as well as Erinus alpinus and Lafuentea rotundifolia were studied with regard to their content of main carbohydrates, iridoids and caffeoyl phenylethanoid glycosides (CPGs). Digitalis and Isoplexis contained sorbitol, cornoside and a number of other phenylethanoid glycosides including the new tyrosol beta-D-mannopyranoside, sceptroside but were found to lack iridoid glucosides. Erinus contained mainly glucose, the new 8,9-double bond iridoid, erinoside, and a number of known iridoid glucosides including two esters of 6-rhamnopyranosylcatalpol, as well as the CPG poliumoside. Finally, Lafuentea was characterized by the presence of glucose, aucubin and cryptamygin B but apparently lacked CPGs. The chemosystematic significance of the isolated compounds is discussed.     

5-O-glucosyldihydroflavones from the leaves of Helicia cochinchinensis

From the leaves of Helicia cochinchinensis, collected on Okinawa Island, seven phenolic glucosides and two terpenic glucosides were isolated. Five of the phenolic glucosides were previously known, being identified with p-coumaric and ferulic acids glucosyl esters, rhodioloside, helicidiol, and naringenin 5-O-beta-D-glucopyranoside. The structures of two other phenolic glucosides, named heliciosides A and B, were elucidated to be 5-O-beta-D-glucosides of 3-hydroxyflavanone, namely aromadendrin and taxifolin, by means of spectroscopic analyses. The two terpenic glucosides were identified with ampelopsisionoside and icariside C1.     

Cyanogenesis in plants and arthropods

Cyanogenic glucosides are phytoanticipins known to be present in more than 2500 plant species. They are regarded as having an important role in plant defense against herbivores due to bitter taste and release of toxic hydrogen cyanide upon tissue disruption, but recent investigations demonstrate additional roles as storage compounds of reduced nitrogen and sugar that may be mobilized when demanded for use in primary metabolism. Some specialized herbivores, especially insects, preferentially feed on cyanogenic plants. Such herbivores have acquired the ability to metabolize cyanogenic glucosides or to sequester them for use in their own defense against predators. A few species of arthropods (within diplopods, chilopods and insects) are able to de novo biosynthesize cyanogenic glucosides and some are able to sequester cyanogenic glucosides from their food plant as well. This applies to larvae of Zygaena (Zygaenidae). The ratio and content of cyanogenic glucosides is tightly regulated in Zygaena filipendulae, and these compounds play several important roles in addition to defense in the life cycle of Zygaena. The transfer of a nuptial gift of cyanogenic glucosides during mating of Zygaena has been demonstrated as well as the involvement of hydrogen cyanide in male attraction and nitrogen metabolism. As more plant and arthropod species are examined, it is likely that cyanogenic glucosides are found to be more widespread than formerly thought and that cyanogenic glucosides are intricately involved in many key processes in the life cycle of plants and arthropods.     

Immunosuppressive constituents from Saussurea medusa.

The methanol extract of Saussurea medusa Maxim afforded two lignans: 2alpha-guaicyl-4-oxo-6alpha-catechyl-3,7-dioxabicyclo [3.3.0]octane and 1alpha-hydroxy-2alpha,4alpha-guaicyl-3,7-dioxabicyclo[3.3.0]octane; two chlorophyll derivatives: 13-epi-phaeophorbide-a and 13-epi-phaeophorbide-a methyl ester; one megastigmane derivative: 3beta-hydroxy-5alpha,6alpha-epoxy-7-megastigmen-9-one, along with 19 known compounds. Their structures were established on the basis of spectroscopic studies.     

Furanoflavonoid glycosides from Pongamia pinnata fruits

Pongamia pinnata fruits afforded three new furanoflavonoid glucosides, pongamosides A-C (1-3), and a new flavonol glucoside, pongamoside D (4). The structures of these compounds were established on the basis of spectroscopic studies. This is the first time that furanoflavone glucosides have been found as naturally occurring compounds.     

Differentiation-dependent levels of benzofuran-type resveratrol dimers in root cultures of Anigozanthos preissii

The level of secondary compounds formed by sterile root cultures of Anigozanthos preissii depends on the differentiation state. Cultures showing shoot formation and accelerated growth are depleted in stilbenes, stilbene glucosides, and phenylphenalenones. Three glucosides of anigopreissin A, a benzofuran-type resveratrol dimer, were isolated from slow-growing cultures and their structures elucidated by spectrometric methods.     

Lignan and megastigmane glycosides from Sauropus androgynus

A lignan diglycoside, (-)-isolariciresinol 3alpha-O-beta-apiofuranosyl-(1-->2)-O-beta-glucopyranoside, and a megastigmane glucoside, sauroposide, were isolated from the aerial part of Sauropus androgynus together with (+)-isolariciresinol 3alpha-O-beta-glucopyranoside, (-)-isolariciresinol 3alpha-O-beta-glucopyranoside, (+)-syringaresinol di-O-beta-glucopyranoside, guanosine and corchoionoside C. The structural elucidations were bases on analyses of physical and spectroscopic data.     

Chromone and chromanone glucosides from Hypericumsikokumontanum and their anti-Helicobacter pylori activities

Chromone glucosides, takanechromones A-C (1, 2 and 5) and chromanone glucosides, named takanechromanones A and B (3 and 4), were isolated from the methanolic extracts of Hypericumsikokumontanum together with 27 known compounds. Their structures were established based on spectroscopic evidence. The isolated compounds and some chromone derivatives were assayed for antimicrobial activity against Helicobacter pylori and cytotoxicity against human cancer cell lines.