Verbascoside is a natural antioxidant extracted from Pedicularis striata Pall (Jueyehesen). After being treated with 20 mumol/l verbascoside, the growth curve and mitotic index of human gastric adenocarcinoma MGc80-3 cells decreased remarkably, cell doubling time was delayed, the cellular growth inhibitory rate amounted to 53.2%, cell surface charge assayed by cell electrophoresis obviously changed, the electrophoresis rate dropped from 3.51 microns/s/v/cm to 2.74, i.e., the percent of retardation reached 28.4%. There was a 75% decrease of the tumorigenicity for the treated cells compared with the untreated cells inoculated subcutaneously in BALB/C nude mice. Scanning electron microscopy revealed that the microvilli on the surface of treated cells had been reduced obviously. It confirmed that verbascoside, similar to DMSO, could reverse MGc80-3 cells' malignant phenotypic characteristics and induced redifferentiation of MGc80-3 cells.

Three new phenylpropanoid glycosides, named luteoside A (3), luteoside B (4), and luteoside C (5), were isolated together with the known compounds verbascoside (1) and isoverbascoside (2) from the roots of the medicinal plant Markhamia lutea. The structures of the new compounds were determined to be 1-O-(3, 4-dihydroxyphenyl)ethyl beta-D-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-4-O- caffeo yl-6-acetyl-beta-d-glucopyranoside, 1-O-(3,4-dihydroxyphenyl)ethyl beta-d-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-6-O- caffeo yl-beta-d-glucopyranoside, and 1-O-(3,4-dihydroxyphenyl)ethyl beta-D-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-6-O- ferulo yl-beta-d-glucopyranoside, respectively, on the basis of chemical and spectroscopic data. All five phenylpropanoid glycosides exhibited potent in vitro activity against respiratory syncytial virus.

Ethanol extracts of Stachys glutinosa L. (Lamiaceae) were investigated for antioxidative properties, as well as antiproliferative action on various cell lines. The antioxidant activities were investigated by ABTS (2,2'-azinobis-3-ethylbenzothiazoline-6-sulphonic acid) assay, DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging, beta-carotene/linoleic acid assay, scavenging of hydrogen peroxide (horseradish peroxidase test), superoxide anion scavenging, and hypochlorous acid scavenging (taurine test). The antioxidant activity was reported as IC50 and reveals antioxidant effects. Antiproliferative effects were measured in vitro on three cell lines: HepG2 (human hepatocarcinoma), MCF7 (breast human adenocarcinoma) and C2C12 (mouse myoblast) cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The ethanol extract induced variations in cell viability on all cell lines tested. At 200 mug/mL, the effects on cell viability were - 23%, - 27% and - 37%, respectively, for C2C12, MCF7 and HepG2.

The methanolic extract from fresh stems of Cistanche tubulosa (Orobanchaceae) was found to show hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. From the extract, three new phenylethanoid oligoglycosides, kankanosides H(1) (1), H(2) (2), and I (3), were isolated together with 16 phenylethanoid glycosides (4-19) and two acylated oligosugars (20, 21). The structures of 1-3 were determined on the basis of spectroscopic properties as well as of chemical evidence. Among the isolates, echinacoside (4, IC(50)=10.2 microM), acteoside (5, 4.6 microM), isoacteoside (6, 5.3 microM), 2'-acetylacteoside (8, 4.8 microM), and tubuloside A (10, 8.6 microM) inhibited D-GalN-induced death of hepatocytes. These five isolates, 4 (31.1 microM), 5 (17.8 microM), 6 (22.7 microM), 8 (25.7 microM), and 10 (23.2 microM), and cistantubuloside B(1) (11, 21.4 microM) also reduced TNF-alpha-induced cytotoxicity in L929 cells. Moreover, principal constituents (4-6) exhibited in vivo hepatoprotective effects at doses of 25-100mg/kg, po.

The total chemical synthesis of isoacteoside (1), 2-(3′,4′-dihydroxyphenyl)ethyl 6-O-caffeoyl-3-O-(α-l-rhamnopyranosyl)-β-d-glucopyranoside, is described. An acteoside acetate with benzyl groups at the catechols (3: 2-(3′,4′-dibenzyloxyphenyl)ethyl 2,6-di-O-acetyl-4-O-[3′,4′-bis(O-benzyl)caffeoyl]-3-O-(α-l-rhamnopyranosyl)-β-d-glucopyranoside) was treated with a solution of methy-lamine in methanol (MeNH2 in MeOH) to perform both deacetylation and caffeoyl migration, affording an isoacteoside derivative with benzyl groups at the catechols4b: 2-(3′,4′-dibenzyloxyphenyl)ethyl 6-O-[3′,4′-bis(O-benzyl) caffeoyl] -3-O-(α-l-rhamnopyranosyl)-β-d-glucopyranoside —in 34% yield. Debenzylation of4b was successfully accomplished by catalytic transfer hydrogenation using 1,4-cyclohexadiene to give the target compound isoacteoside (1) in 54% yield.1H and13C nuclear magnetic resonance spectral data of the synthesized isoacteoside (1) were identical with those of the natural isoacteoside isolated fromPaulownia tomentosa (Thumb.) Steud.]]>

Anomerization, which involves cleavage and formation of the anomeric C-O bond, is of fundamental importance in the carbohydrate chemistry. Herein, the unexpected gold(I)-catalyzed anomerization of glycosyl ortho-alkynylbenzoates has been studied in detail. Especially, crossover experiments in the presence of an exogenous isochromen-4-yl gold(I) complex confirm that the anomerization proceeds via the exocleavage mechanism, involving (surprisingly) the addition of the isochromen-4-yl gold(I) complex onto a sugar oxocarbenium (or dioxolenium) and an elimination of LAu(+) from the vinyl gold(I) complex. The inhibitory effect of the exogenous isochromen-4-yl gold(I) complex when in stoichiometric amount on the anomerization has guided us to disclose an isochromen-4-yl gem-gold(I) complex, which is inactive in catalysis but in equilibrium with the monogold(I) complex and the LAu(+) catalyst. The proposed key intermediate in the anomerization, a transient glycosyloxypyrylium species, is successfully trapped via a cycloaddition reaction with n-butyl vinyl ether as a dienophile. SN2-like substitution of the initially formed glycosyloxypyrylium intermediate has then been achieved to a large extent via charging with acceptors in an excess amount to lead to the corresponding glycosides in a stereoselective manner.

The methodological developments in gold(i)- and gold(iii)-catalyzed glycosylation reactions are fully surveyed, which exploit the special alkynophilicity or the Lewis acidity of the gold cationic complexes. The application of the new methods in the total synthesis of naturally occurring glycoconjugates and glycans is comprehensively reviewed, with a focus on glycosylation of various complex aglycones.

Naturally occurring glycans and glycoconjugates have extremely diverse structures and biological functions. Syntheses of these molecules and their artificial mimics, which have attracted the interest of those developing new therapeutic agents, rely on glycosylation methodologies to construct the various glycosidic linkages. In this regard, a wide array of glycosylation methods have been developed, and they mainly involve the substitution of a leaving group on the anomeric carbon of a glycosyl donor with an acceptor (a nucleophile) under the action of a particular promoter (usually a stoichiometric electrophile). However, glycosylations involving inherently unstable or unreactive donors/acceptors are still problematic. In those systems, reactions involving nucleophilic, electrophilic, or acidic species present on the leaving group and the promoter could become competitive and detrimental to the glycosylation. To address this problem, we applied the recently developed chemistry of alkynophilic gold(I) catalysts to the development of new glycosylation reactions that would avoid the use of the conventional leaving groups and promoters. Gratifyingly, glycosyl o-alkynylbenzoates (namely, glycosyl o-hexynyl- and o-cyclopropylethynylbenzoates) turned out to be privileged donors under gold(I) catalysis with Ph3PAuNTf2 and Ph3PAuOTf. The merits of this new glycosylation protocol include the following: (1) the donors are easily prepared and are generally shelf-stable; (2) the promotion is catalytic; (3) the substrate scope is extremely wide; (4) relatively few side reactions are observed; (5) the glycosylation conditions are orthogonal to those of conventional methods; and (6) the method is operationally simple. Indeed, this method has been successfully applied in the synthesis of a wide variety of complex glycans and glycoconjugates, including complex glycosides of epoxides, nucleobases, flavonoids, lignans, steroids, triterpenes, and peptides. The direct glycosylation of some sensitive aglycones, such as dammarane C20-ol and sugar oximes, and the glycosylation-initiated polymerization of tetrahydrofuran were achieved for the first time. The gold(I) catalytic cycle of the present glycosylation protocol has been fully elucidated. In particular, key intermediates, such as the 1-glycosyloxyisochromenylium-4-gold(I) and isochromen-4-ylgold(I) complexes, have been unambiguously characterized. Exploiting the former glycosyloxypyrylium intermediate, SN2-type glycosylations were realized in specific cases, such as beta-mannosylation/rhamnosylation. The protodeauration of the latter vinylgold(I) intermediate has been reported to be critically important for the gold(I) catalytic cycle. Thus, the addition of a strong acid as a cocatalyst can dramatically reduce the required loading of the gold(I) catalyst (down to 0.001 equiv). C-Glycosylation with silyl nucleophiles can proceed catalytically when moisture, which is sequestered by molecular sieves, can serve as the H(+) donor for the required protodeauration step. Indeed, the unique mechanism explains the merits and broad applicability of the present glycosylation method and provides a foundation for future developments in glycosylation methodologies that mainly involve improving the diastereoselectivity and catalytic efficiency of glycosylations.

1) and Notoginsenoside R1 (2) are two representative dammarane type protopanaxatriol-6,20-O-bisglycosides occurring widely founded in Panaxginseng. Ginsenoside Re (1) showed potent antioxidative, anti-inflammatory and antihyperlipemia activities, and Notoginsenoside R1 (2) showed potent antioxidative and antiinflammatory activities, so it would be helpful to synthesize these homogeneous natural products in appreciable amounts by accelerating their structure-activity relationship study. As a persistent effort on the chemical syntheses of the diverse ginsenosides in our group, we report herein the efficient syntheses of these two complex natural products. Thus, based on the reactivity sequence of the four hydroxyl groups (i.e., 12-OH > 3-OH > 6-OH >> 20-OH) of the protopanaxatriol aglycon, an orthogonal and efficient protecting group strategy was applied to distinguish these hydroxyl groups. The subsequent installation of the 6,20-O-bisglycosides are challenging, given the poor reactivity of the secondary 6-OH and tertiary 20-OH, moreover, with the latter being labile toward acidic conditions. Taking advantage of the neutral conditions of the Au(I)-catalyzed glycosylation reaction (0.3 equiv. Ph3PAuNTf2, 4 Å MS, CH2Cl2, r.t.), the glycosylation of the acid-labile 20-hydroxyl group was achieved effectively in a high 84% yield firstly. To be convergent for the syntheses of these two ginsenosides, the 6-O-disaccharide residues were installed in a stepwise manner. For the glycosylation of the 6-OH of protopanaxatriol, a higher loading of the catalyst Ph3PAuNTf2 (0.5 equiv.) was employed in order to increase the glycosylation yield while reduce the orthoester formation, thus, the desired 6β-O-glucosides were prepared in satisfactory yields (77%~83%). Both terminal α-L-Rha/β-D-Xyl moieties at the 2' position of 6-O-glc were installed efficiently under 0.2 equiv. Ph3PAuNTf2 catalyzing condition (ClCH2CH2Cl, 5 Å MS, 40℃) with 86% and 81% yields, respectively. After global deprotection, Ginsenoside Re (1) and Notoginsenoside R1 (2) were synthesized with the longest 13 linear steps in 5.1% and 4.5% overall yields, respectively.]]>

O-Glc'糖基2位羟基连续三次糖苷化,以最长线性13步分别以5.1%和4.5%的收率合成了天然双糖基达玛烷皂苷Ginsenoside Re（1）和Notoginsenoside R1（2）.]]>

O-β-D-glucuronide (1) and scutellarin (scutellarein-7-O-β-D-glucuronide, 2) are two major flavone glucuronide components occurring in breviscapines, which are prepared from the traditional Chinese herb Erigeron breviscapus. These two flavone glycosides show potent anti-oxidative, anti-inflammatory and neuroprotective activities in various evaluations. Synthesis of these natural glycosides in an efficiently manner would facilitate studies on their structure activity relationships. As a persistent effort on the chemical syntheses of the diverse glycoconjugates from traditional Chinese herbs in our group, we report herein the synthesis of these two representative flavone O-glucuronides. It is known that the solubility of flavone compounds is rather low and this property would greatly hinder their glycosylation reactions. In order to increase the solubility of the flavone derivatives in the glycosylation solvents, hexanoyl and benzyl groups were selected as the permanent protecting groups for the hydroxyl groups of apigenin (7) and scutellarein (8). The construction of the phenolic O-glucuronide is known to be a difficult task, especially the glycosylation of the poorly nucleophilic 7-hydroxyl group which locates at the para-position of the flavone carbonyl group. We achieved the glycosylation of the flavone 7-OH with 2,3,4-tri-O-benzoyl-6-O-TBDPS-glucopyranosyl ortho-alkynylbenzoate (9) under the catalysis of Ph3PAuNTf2 (0.2 equiv., 4 ? MS, CH2Cl2, r.t., 5 h) in excellent yields. After that, the 6-O-TBDPS groups were removed, and the requisite glucuronides were then elaborated by oxidation of the resulting 6-OH under the conditions of DAIB/TEMPO (CH2Cl2/H2O, V∶V=2∶1, r.t.) in good yields. After global deprotection, the desired products apigenin-7-O-β-D-glucuronide (1) and scutellarin (2) were obtained in overall yields of 36% (5 steps) and 7% (9 steps), respectively, from the starting flavone aglycones. Following the same strategy, four naturally occurring flavone-7-O-glycosides, namely apigetrin (3), plantaginin (4), apigenin 7-O-β-D-xylopyranoside (5) and apigenin 7-O-α-L-rhamnopyranoside (6), were smoothly synthesized in 4~7 steps with the overall yields of 61%, 13%, 58% and 61%, respectively.]]>

O-β-D-glucuronide, 1)和乙素(scutellarin, scutellarein-7-O-β-D-glucuronide, 2)是灯盏花素(breviscapine)中的两种主要黄酮苷成分, 具有抗氧化、抗肿瘤和治疗老年痴呆等生理活性; 大波斯菊苷(apigetrin, 3)、车前子苷(plantaginin, 4)、apigenin 7-O-β-D-xylopyranoside (5)、apigenin 7-O-α-L-rhamnopyranoside (6)等黄酮-7-O-糖苷也具有相似的结构和生理活性. 本工作针对黄酮苷元(芹菜素7和野黄芩素8)溶解度差、7位羟基酸性强而亲核性较弱以及糖醛酸糖基化给体反应活性较弱的问题, 综合利用使苷元有效增溶的保护基策略、金(I)催化的糖苷化方法和后期糖醛酸氧化策略, 高效构建了黄酮-7-O-葡萄糖醛酸结构, 并经统一的保护基脱除完成了灯盏花甲素(1) (36%)和乙素(2) (7%)的合成. 采用相似的策略, 从苷元出发分别以4~7步完成了天然黄酮-7-O-糖苷3~6的合成.]]>

A highly effective and versatile glycosylation method is developed, which uses 3,5-dimethyl-4-(2'-phenylethynylphenyl)phenyl (EPP) glycosides as donors and NIS/TMSOTf as promoter and proceeds via an unprecedented dearomative activation mechanism.

We report on a diastereoselective synthesis of six derivatives of caffeoyl- and feruloyl-muco-quinic acids. All the muco-quinic acid derivatives were obtained in excellent yield in five steps starting from quinic acid, caffeic acid and ferulic acid. Allyl ether protection of trans-hydroxy cinnamic acids was here introduced to chlorogenic acids synthesis. We show that muco-quinic acid derivatives, which are formally diastereoisomers of chlorogenic acids, can be readily distinguished by their tandem mass spectra.

AbstractTreatment of saccharidic polyols in ethyl acetate with catalytic sulfuric acid leads to the corresponding primary monoacetate derivatives in good yields. The transesterification was realized by simple stirring without rigorous exclusion of moisture or oxygen. Our protocol is applicable to the regioselective monoacetylation of amino sugars having different substituents at the 2-positions.Graphical abstract]]>