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An open-air palladium-catalyzed O-glycosylation was developed using glycals and arylboronic acids with base additives at ambient conditions. The novel approach enabled facile access to various

A novel tactic for the regioselective O-alkylation of 2-pyridones has been realized through palladium catalysis facilitated by silver carbonate in moderate to high yields, the coordination effect between palladium and nitrogen on the pyridine ring plays a versatile role.

A mild and highly efficient Ugi-3CR using a novel Cu-COOH@MOF-6 as the catalyst has been developed, which provides facile access to α-amino amides. The recycling test and XRD images showed that the catalytic system has good stability and recyclability.

An effective regiodivergent synthesis toward 1- and 3-thiosugars was achieved through palladium and cobalt catalysis, respectively. β-1-Thiosugars were obtained from 3,4-O-carbonate-glycals and var...

An exclusive asymmetric reduction of CO bonds of 2-arylidene four-, five-, six-, and seven-membered cycloalkanones has been studied systematically. The asymmetric transfer hydrogenation was performed using a robust and commercially available chiral diamine-derived ruthenium complex as a catalyst and HCOOH/Et3N as a hydrogen source under mild conditions, giving 51 examples of chiral exocyclic allylic alcohols in up to 96% yield and 99% ee. This method was also applicable to the gram-scale synthesis of the active intermediates of the anti-inflammatory loxoprofen and natural product (−)-goniomitine.

A new methodology of stereoselective C-glycosylation has been developed with 3,4-O-carbonate glycals and boronic acids, catalyzed by 1,2-bis(phenylsulfinyl)ethane palladium(II) acetate under open-air conditions at room temperature. This mild method is simple in operation, wide in substrate range, and tolerant in alcoholic/phenolic hydroxyl and amino groups. High to excellent yields were observed for all substrates tested, with the driving force mainly contributed by decarboxylation. Meanwhile, the high 1,4-trans-selectivity was achieved by steric effects as proposed.

Direct N-glycosylation between glycals and amides/amines was achieved with exclusive stereoselectivity in moderate to high yields. Various amides, amines, and 3,4-O-carbonate-glycals were tolerated, and unique β-N-glycosides were obtained. The strategy was based on palladium-catalyzed decarboxylative allylation, and the high 1,4-cis-selectivity was proposed because of the hydrogen bonding effect. Notably, all the synthesized products were subjected to preliminary bioactivity studies, revealing that three compounds were cytotoxic to tumor cells and nontoxic to normal human cells.

A new methodology of stereoselective

The interaction mechanisms of a series of bisabolonalone hydrazone carboxamides as H+,K+-ATPase reversible inhibitors were studied by molecular docking, QM/MM calculation, and MM/GBSA binding free energy analysis methods. The correlation coefficient, R, between calculated ΔG bind (the binding free energy with H+,K+-ATPase homology model) and experimental pIC50 (negative logarithms of 50% inhibition concentration) of ligands is −0.9386. A suitable molecular volume of ligand is needed to dock into the whole binding pocket, which includes Gln127–Leu141 in the loop of TM1–TM2; Arg328–Ala335 in the loop of TM4; Tyr799–Thr815 in the loop of TM5–TM6; Trp899–Phe917 in the loop of TM7–TM8; Leu921–Tyr928 in the loop of TM8; and Asn986–Asn989 in the loop of TM9–TM10. By the decomposed energy comparisons of residues in binding sites, the naphthyl group substituting benzene ring in bisabolonalone hydrazone carboxamides could increase the hydrophobic interaction with Cys813, which is a very important binding site for enhancing the inhibition activity. In addition, Asp137 is another key residue binding with ligand through the hydrogen bond and electrostatic interactions. The results of this analysis could help in further rational design of novel H+,K+-ATPase reversible inhibitors.

An inexpensive and effective cobalt coordinated conjugated microporous polymer (Co-CMP-2) made up from cross-linked an ethanediamine-based salen ligand with 1,3,5-triethynylbenzene. Co-CMP-2 exhibited extremely high catalytic efficiency in the synthesis of cyclic carbonates from CO2 and epoxides, which is superior to that of previously reported Co-CMP. Co-CMP-2 achieved a TOF of 23300 h−1 for ethylene carbonate. Moreover, the catalyst can be reused more than 10 times without significant loss in activity.

Covalent triazine-based frameworks (CTFs) are important microporous materials with a wide range of applications. Here, we demonstrate an environmentally benign and economic synthetic pathway to CTFs. The monomers used for CTFs, aromatic nitriles, were obtained by cyanation using nontoxic potassium hexacyanoferrate (Ⅱ) in place of commonly used toxic cyanides. Then, the CTFs were synthesized by trimerization of the corresponding cyano monomers in molten zinc chloride. A series of CTFs was synthesized, and the highest Brunauer-Emmett-Teller surface area measured in this series was 2404 m 2 /g. Among the synthesized CTFs, CTF DCP exhibited excellent CO 2 adsorption properties, with a CO 2 uptake of 225 mg/g at 0℃.

Trametenolic acid B (TAB) was a lanostane-type triterpenoid isolated from the trametes lactinea (Berk.) Pat. We have previously reported that extract from trametes lactinea (Berk.) Pat and TAB could efficiently improve learning and memory ability of the cerebral ischemia injury rats and suppress mitochondrial-mediated apoptosis in hydrogen peroxide damaged SH-SY5Y cells. However, the potential mechanisms have not been fully understood yet. The current study was to further investigate the protective effect of TAB on oxygen glucose deprivation/reoxygenation (OGD/R)-damaged SH-SY5Y cells and cerebral ischemia/reperfusion (I/R) injury rats, as well as its mechanisms involved. Cell experiments demonstrated that TAB (10, 20 and 40 μg/mL) protected OGD/R-induced SH-SY5Y cell injury by promoting cell proliferation and suppressing LDH leakage; Meanwhile, the results in vivo showed that TAB (20, 40 and 80 mg/kg) might significantly ameliorate the neurological deficit score, cerebral edema, neuronal cell loss and apoptosis, suppress cerebral infarction volume of the cerebral I/R injury rats. Further studies in vitro and in vivo indicated TAB could efficiently reduce OGD/R-damaged SH-SY5Y cell and cerebral I/R rat serum ROS, LDH and MDA levels, elevate SOD, GSH-Px and CAT activities, downregulate miR-10a mRNA and Bax, cytochrome C, cleaved-caspase-3 and cleaved-caspase-9 protein expressions, upregulate p-PIK3CA, p-Akt, p-mTOR, Bcl-2, pro-caspase-9 and pro-caspase-3 protein expressions and p-PIK3CA/PIK3CA, p-Akt/Akt, p-mTOR/mTOR ratios (P

Bisabolangelone is the main active ingredient of Angelica polymorpha, which has the good pharmacological activities such as anti-celialgia, anti-dysmenorrhea and anti-gastralgia. In this study, the neuroprotective effect of bisabolangelone against hydrogen peroxide (H2O2)-induced neurotoxicity in human neuroblastoma cells was studied. The binding capacity between bisabolangelone and calcium channel was calculated by molecular docking method, and calcium concentration was detected by the calcium fluorescent probe of Fura-2 AM. The results indicated that bisabolangelone had a good neuroprotective effect on nerve cells by interacting with calcium channels, mainly blocking the voltage-gated calcium channels, suppressing calcium releasing from the calcium store.

A novel gold-catalyzed C-glycosylation has been developed to gain access to α,(Z)-selective C-vinyl glycosides, starting from readily available glycals and propargylic carboxylate. This reaction involves a tandem intermolecular gold-catalyzed 1,3-acyloxy migration/Ferrier rearrangement with the involvement of allenic ester as the glycosyl acceptor. A wide range of substrate scope with good to excellent yields was achieved with complete diastereoselectivity. Ministry of Education (MOE) National Research Foundation (NRF) Accepted version We thank the Ministry of Education (MOE 2013-T3-1-002), National Research Foundation (NRF2016NRF-NSFC002-005), Nanyang Technological University, Singapore (RG14/16), China Scholarship Council (No. 201508420062), and Youth Talent Development Foundation of China Three Gorges University for their financial support. Dr. Yongxin Li and Dr. Ganguly Rakesh in the division of chemistry and biological chemistry, Nanyang Technological University are also acknowl-edged for X-ray analysis.

A high-efficient and stereo-specific approach for the preparation of biologically important (E)-2-styryl-tetrahydrobenzo[d]thiazoles has been developed via TMSCl promoted direct sp3 C-H alkenylation of 2-methyl-5,6-dihydrobenzo[d]thiazol-7(4H)-one under metal-free conditions. Seventeen target compounds were synthesized in excellent yields of 82% –98% under the optimal conditions of 300 mol% TMSCl at 110°C for 2 h, and their chemical structures were elucidated by IR, NMR, ESI-MS, elemental analyses and X-ray crystallography analysis. A plausible mechanism was also proposed, and this method provided a good functional group conversion for the sp3 C-H substrates.

Seeking a strategy for triggering the cryptic natural product biosynthesis to yield novel compounds in the plant-associated fungus Xylaria sp., the effect of culture conditions on metabolite production was investigated. A shift in the production of five known cytochalasin-type analogues 1–5 to six new α-pyrone derivatives, xylapyrones A–F (compounds 6–11), from a solid to a liquid medium was observed. These compounds were identified by analysis of 1D and 2D NMR and HRMS data. Compounds 1–3 showed moderate cytotoxicity against HepG2 and Caski cancer cell lines with IC50 values ranging from 25 to 63 μM and compounds 4–11 were found to be inactive, with IC50 values &gt, 100 μM.

Hispolon was the main antitumor active ingredient in Phellinus sensu lato species. In order to confirm the dual regulating estrogenic ingredient and obtain more effective natural estrogen replacement drugs, hispolon was separated from Phellinus lonicerinus (Bond.) Bond. et sing. Hispolon exhibited significant anti-proliferative effect against estrogen-sensitive ER (+) MCF-7 cells in the absence of estrogen, and exhibits antagonistic effects on 17β-estradiol (E2)-induced MCF-7 cell proliferation when E2 and the different concentrations of hispolon were treated simultaneously. Hispolon also inhibited the proliferation of estrogen-negative ER (−) MDA-MB-231 cells at the concentration of 5.00 × 10− 5 M. The yeast two-hybrid experiments showed that hispolon had strong and non-selective effects on the estrogen receptor (ER) α and ERβ at a concentration of 1.00 × 10− 6 M. The ERβ-binding ability of hispolon was larger than ERα in the concentration range of 1.00 × 10− 9 M and 1.00 × 10− 7 M. Hispolon could increase the body weight coefficient, serum E2 and progesterone contents in immature female mice at dose of 9.10 × 10− 6 mol/kg, and increase coefficient of thymus and spleen in mice. The Gscores of hispolon-ERα and hispolon-ERβ docked complexes were − 7.93 kcal/mol and − 7.79 kcal/mol in docking simulations. Hispolon presented dual regulating estrogenic activities, which showed estrogenic agonist activity at low concentration or lack of endogenous estrogen, and the estrogenic antagonistic effect was stimulated at high concentrations or too much endogenous estrogen. Hispolon could be used for treating the estrogen deficiency-related disease with the benefit of non-toxic to normal cells, good antitumor effects and estrogenic activity.

Zinc-coordinated conjugated microporous polymers (zn-cmps), prepared by linking salen zinc and 1,3,5-triethynylbenzene, exhibit extraordinary activities (turnover frequencies of up to 11600 h(-1)), broad substrate scope, and group tolerance for the synthesis of functional organic carbonates by coupling epoxides with co2 at 120 degrees c and 3.0 mpa without the use of additional solvents. the catalytic activity of zn-cmp is comparable to those of homogeneous catalysts and superior to those of other heterogeneous catalysts. this catalyst could be reused more than ten times without a significant decrease in performance.

We reported a bifunctional material, Cr-salen implanted conjugated microporous polymer (Cr-CMP), which is able to capture excellent CO2 amounts and has a remarkable catalytic activity towards the cycloaddition reaction of CO2 to epoxides forming cyclic carbonates at mild conditions without additional solvents. This heterogeneous Cr-CMP catalyst has a superior catalytic activity to its related homogeneous catalyst and can be reused more than ten times without a significant decrease in catalytic activity.

Trametenolic acid B (TAB), the bioactive component in the Trametes lactinea (Berk.) Pat, was reported to possess cytotoxic activities and thrombin inhibiting effects. This study was performed to investigate the effects of TAB on H(+)/K(+)-ATPase and gastric cancer. The H(+)/K(+)-ATPase inhibitory activity was determined by gastric parietal cells. Compared to the normal control group, TAB (10, 20, 40 and 80 μg/mL) inhibited the H(+)/K(+)-ATPase activity by 15.97, 16.96, 24.86 and 16.25%, respectively. In the study, 36 Kunming mice were randomly divided into six groups: control, model, TAB-L (TAB, 5 mg/kg/day, i.g.), TAB-M (TAB, 20 mg/kg/day, i.g.), TAB-H (TAB, 40 mg/kg/day, i.g.) and omeprazole (OL, 10 mg/kg/day, i.g.). All mice except the control group were administrated with anhydrous alcohol (5.0 mL/kg, i.g.) for induced gastric-ulcer 1h after the 5th day. At the same time, the control mice were given the same volume of physiological saline. After 4h, TAB was evaluated for H(+)/K(+)-ATPase inhibitory activities of ulcerative gaster, gastric ulcer index and ulcer inhibition. In vitro, the anti-proliferation effect of TAB to gastric cancer cell (HGC-27) in acid environment was detected by MTT, and the apoptosis morphological changes were also observed by Hoechst 33258 dye assay. The results indicated that TAB inhibited moderately H(+)/K(+)-ATPase activity in vitro. Compared to the model group, TAB showed anti-ulcer effects in gastric tissue with the dosages of 20 and 5 mg/kg in vivo. Apart from that, TAB could selectively inhibit gastric cancer cell viability and reduce cell apoptosis against HGC-27 cells at low doses in acid environment.

we first report the application of 3-acyl-5-hydroxybenzofurans as a scaffold to develop potential drugs for breast cancer. seven novel derivative compounds were synthesized by using a microwave-assisted synthesis method. those compounds exhibited different antiproliferation against human breast cancer mcf-7 cells, with the best activity of ic50=43.08 mu m for compound 1. a quantum mechanics polarized ligand docking (qpld) study was carried out to investigate the binding interactions between these compounds and estrogen receptor alpha (er alpha). the simulation results showed that the trend of receptor-ligand binding interactions was same as that of their antiproliferative activities. a detailed analysis indicated that compound 1 possesses the highest van der waals and hydrogen bond interactions compared to the other six compounds and better inhibitors are achievable by enhancing the hydrogen bond interactions. based on these results, we addressed that 3-acyl-5-hydroxybenzofuran is an attractive scaffold for designing drugs against breast cancer. (c) 2013 elsevier ltd. all rights reserved.

A highly solid-emissive Boron–Fluorine scaffold with two conjugated alkyne groups ( BOPIM-S ) is facilely synthesized, which shows enhanced fluorescent intensity compared to the BOPIM dye without alkyne units. According to X-ray single crystal analysis, the terminal alkyne groups interact with atoms B, F, C and N on neighbouring molecules, producing a rigid rectangular structure, which helps to avoid energy loss via non-irradiative decay. Furthermore, BOPIM-S can undergo copper catalysed alkyne–azide-cycloaddition (CuAAC) chemistry with aromatic azides to produce conjugated molecules with high yields. According to absorption and fluorescent measurements, all these compounds synthesized by CuAAC emit large Stokes shift (over 100 nm) both in solution and in solid state. But the electronic environments of terminal aromatic rings slightly affect their photophysical properties.

Eleven triazolyl substituted tetrahydrobenzofuran derivatives were synthesized in high yields as novel H+/K+-ATPase inhibitor via one-pot CuI-catalyzed three-component click reaction of azide, secondary amine and 3-bromopropyne under mild conditions in water. Their structures were characterized by NMR, IR, ESI-MS, elemental analysis and single-crystal X-ray diffraction analysis. Most of the target compounds exhibited better H+/K+-ATPase inhibitory activity than commercial omeprazole with IC50 values less than 15 µmol·L−1. The initial structure-activity analysis suggested that the triazole substituted by cycloalkyl, aromatic ring or O-containing side-chain seemed to be beneficial for enhancing the activity.

Pharmacophore and three-dimensional quantitative structure–activity relationship (3D-QSAR) model of 106 aryl diphenolic azoles as estrogen receptor-β ligands were proposed. The best pharmacophore model, five-site model including two hydrogen bond donors and three aromatic rings, has been established. The biological activity values (pIC50) and classification (active or inactive) of compounds were predicted by 3D-QSAR model. The model correlation coefficient (R 2) is 0.9623. The classification accuracies in predicting for training, test, and total datasets are 97.5, 84.6, and 94.3 %, respectively. The 3D-QSAR model maps revealed that hydrogen bond donor, hydrophobic, and electron-withdrawing fields would be the essential factors for designing new ligands with higher biological activity. The results indicate that the combination of pharmacophore and 3D-QSAR analyses could be a powerful modeling tool for finding novel estrogen receptor-β ligands.

Two new thiazole and thiadiazole alkaloids, penicilliumthiamine A and B (2 and 3), were isolated from the culture broth of Penicillium oxalicum, a fungus found in Acrida cinerea. Their structures were elucidated mainly by spectroscopic analysis, total synthesis and X-ray crystallographic analysis. Biological evaluations indicated that compound 1, 3a and 3 exhibit potent cytotoxicity against different cancer cell lines through inhibiting the phosphorylation of AKT/PKB (Ser 473), one of important cancer drugs target.

Three new steroidal compounds with polyhydroxy groups, tupisteroide A-C (1-3), were obtained from the roots of Tupistra chinensis, together with one known compound (4) that was isolated from this plant for the first time. The structures of tupisteroide A-C were determined on the basis of one- and two-dimensional NMR spectroscopy, including (1) H-(1) H Correlation Spectroscopy, Heteronuclear Multiple Bond Correlation, and Heteronuclear Single Quantum Coherence experiments. The isolated compounds were evaluated for their cytotoxic activities against A549, HepG2, and CaSki cancer cell lines in vitro. Among them, compounds 1, 2, and 4 did not show significant inhibitory activity, but compound 3 showed cytotoxicity against A549 cancer cell lines with IC(50) values of 25.0 μM.

Nine bisabolangelone reduction derivatives were synthesized and separated as potential anti-ulcer agent. Their structures were characterized by 2D NMR, IR, ESI-MS, elemental analysis and single-crystal X-ray diffraction analysis. Preliminarily H+/K+-ATPase activity evaluation indicated that all the target compounds had a certain inhibitory effect, and compounds II and IV exhibited the better inhibitory activity against H+/K+-ATPase than bisabolangelone and the commercial omeprazole with the IC50 of 23.21 and 65.32 μmol/L, respectively. The initial structure-activity analysis suggested that the presence of carbonyl group in six-membered ring and double bond in side-chain seemed to be necessary to the activity.

Ethnopharmacological relevance Chinese traditional medicine Rhizoma drynariae (Gusuibu) is widely used for clinically treating osteoporosis and bone non-union. Naringin and its active metabolite naringenin are the main active ingredients of Rhizoma drynariae total flavonoids. Aim of the study The purpose of this paper is to confirm estrogenic and anti-estrogenic activity of naringin and naringenin, and provide the basic data to further study for the dose–effect relationship and the mechanism for Rhizoma drynariae in treatment of osteoporosis and other estrogen deficiency-related diseases. Materials and methods Naringin was extracted from Rhizoma drynariae. Naringin and its metabolin naringenin were tested estrogenic and anti-estrogenic activities through the experiment of cell proliferation and uterus weight gain in mice. Their estrogen-receptor binding abilities were tested by yeast two-hybrid experiment and nuclear receptor cofactor assays (RCAS) experiment, and their possible binding sites for ERβ were performed by computer aided molecular docking technology. Results Naringin and naringenin showed significant effects on the proliferation of estrogen-sensitive ER(+) MCF-7 cells in the absence of estrogen. Induction increased proliferation as the drug concentration, and the strongest proliferation appeared at a concentration of 8.6 × 10−5 M. When estradiol (10−10 M) and the different concentrations of naringin or naringenin were treated at the same time, naringin and naringenin could result in antagonistic effects on estradiol-induced MCF-7 cell proliferation, but they did not significantly affect proliferation of estrogen-insensitive ER(−) MDA-MB-231 cells. Naringin and naringenin exhibited higher binding capacity to estrogen receptor β (ERβ) than estrogen receptor α (ERα) in yeast two-hybrid experiments and nuclear receptor cofactor assays (RCAS) experiment. Docking simulation between naringin/naringenin and ERβ were performed, and the corresponding binding free energies of naringin–receptor and naringenin–receptor docked complexes were −7.95 and −10.45 kcal/mol. Hydrogen bonds were found between naringin and the amino acid residues Lys304 and His308. The oxygen atom (O11) of naringenin formed hydrogen bond to Arg346, and there may be hydrophobic space interactions between phenyl group (C13–C18) of naringenin and the amino acid residues Leu298, Met336, Met340, Phe356, Ile376 and Leu380. Conclusions Naringin and naringenin revealed a double directional adjusting function of estrogenic and anti-estrogenic activities. Both of them showed estrogenic agonist activity at low concentration or lack of endogenous estrogen. On the other hand, they also acted as estrogenic antagonists at high concentrations or too much endogenous estrogen. They produced estrogenic and anti-estrogenic effects primarily through selectively binding with ERβ, which could prevent and treat osteoporosis with the mechanism of estrogenic receptor agitation. This paper confirmed the estrogenic and anti-estrogenic activity of naringin and naringenin, and further studies were still essential to study their dose–effect relationship and the anti-osteoporosis mechanism for Rhizoma drynariae in the treatment of osteoporosis and other estrogen deficiency-related diseases.

The homology model of human gastric H+/K+-ATPase has been produced based on the template provided by pig gastric H+/K+-ATPase (PDB code: 3IXZ). After molecular mechanics optimization, induced-fit docking simulation between gastric H+/K+-ATPase and bisabolangelone that has significantly inhibition activity of H+/K+-ATPase was performed. The results of ligand docking showed that the binding pocket involves the amino acid residues Asp101, Asp102, Tyr105, Leu106, Val296, Phe297, Met299, Ala300, Tyr764, Tyr767, Leu774, Gly777, Cys778, Ile779, Gln889, Tyr893, and Ile952. The hydrogen bonds are formed between bisabolangelone and the amino acid residues Cys778, Gln889, and Tyr893.

To develop more effective antitumor steroidal drugs, we synthesized a library including twenty-two novel cytotoxic 2-alkyloxyl substituted (25R)-spirostan-1,4,6-triene-3-ones and corresponding 1,2,3-triazoles through an abnormal monoepoxide ring-opening/elimination and 'click' reactions. After the cytotoxic evaluations against HepG2, Caski and HeLa cell lines, three steroidal triazoles 5b, 5f and 5m in this library were found to possess potent anti-proliferative effects against Caski cells with the half-inhibitory concentrations (IC50) of 9.4-11.8 mu M. The high-efficient and straightforward process was attractive feature for facile preparation of anti-tumor steroidal triazoles. (C) 2015 Elsevier Ltd. All rights reserved.

The catalyst is reused for more than ten times without significant loss of its catalytic activity.

In this publication, we design and report the synthesis of calix[4]arene-based β-diketo derivatives as novel HIV-1 integrase (IN) inhibitors. The target compounds were obtained using Claisen condensation, and their structures were characterized by NMR and ESI-MS. Preliminary bioassays showed that calix[4]arene-based β-diketo derivatives inhibit strand transfer (ST) with IC50 values between 5.9 and 21.2 µM. Docking studies revealed the predominant binding modes that were distinct from the binding modes of raltegravir, which suggests a novel binding region in the IN active site. Moreover, these compounds are predicted not to interact with some of the key amino acids (GLN148 and ASN155) implicated in viral resistance. Therefore, this series of compounds can further be investigated for a possible chemotype to circumvent resistance to clinical HIV-1 IN inhibitors.

A CuI-catalyzed three-component alkyne-azide cycloaddition in the presence of an excess of secondary amine is used for the synthesis of triazolyl-substituted tetrahydrobenzofuran derivatives.

Among a variety of reduction derivatives, the compounds (I) and (II) exhibit better inhibitory activity against H+/K+-ATPase than omeprazole.