- Synthesis of ethylene bis [(2-hydroxy-5,1,3-phenylene) bis methylene] tetraphosphonic acid and their anticorrosive effect on carbon steel in 3%NaCl solution
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The inhibition performance of the newly synthesized Ethylene bis [(2-hydroxy-5,1,3-phenylene) bis methylene] tetraphosphonic acid (ETPA) toward carbon steel in 3% NaCl was investigated at different concentrations using potentiodynamic polarization (PDP) and impedance spectroscopy (EIS) methods. It was found that the inhibition capability was increased with increasing inhibitor dose and reach 92% at 10?3 mol/L. Also, Polarization curves showed that ETPA acts as a mixed type inhibitor with predominantly control of anodic reaction. The new inhibitor was investigated by different spectroscopic methods such as 1H, 13C and 31PNMR. The quantum parameters such as absolute electronegativity (χ), energy gap ΔE (EHOMO-ELUMO), global softness (σ), global hardness (η), electrophilicity index (ω) and the number of transfer electrons (ΔN) are calculated by density functional theory (DFT). The experimental also correlated with density functional theory results. The calculations show that ETPA has high density of negative charge located on the oxygen atoms of the phosphonate group facilitating the adsorption of ETPA on the surface of carbon steel. The inhibition efficiency of ETPA was discussed in terms of blocking of electrode surface by adsorption of ETPA molecules through active centers. The adsorption of ETPA on the surface of carbon steel obeyed the Langmuir isotherm paradigm.
- Sait,Aliouane,Toukal,Hammache,Al-Noaimi,Helesbeux,Duval
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Read Online
- Synthesis of Indole-, Benzo[ b]thiophene-, and Benzo[ b]selenophene-Based Analogues of the Resveratrol Dimers Viniferifuran and (±)-Dehydroampelopsin B
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A convenient synthetic strategy to obtain viniferifuran and (±)-dehydroampelopsin B analogues based on the heterocyclic cores of indole, benzo[b]thiophene, and benzo[b]selenophene is presented. The key transformations utilized in the described syntheses include Sonogashira couplings, Cacchi and alkyne electrophilic cyclizations, Horner-Wadsworth-Emmons (HWE) reaction, chemoselective Suzuki-Miyaura couplings, and acid-promoted intramolecular cyclization to form the seven-membered ring of (±)-dehydroampelopsin B.
- Krzyzanowski, Adrian,Saleeb, Michael,Elofsson, Mikael
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- Chemo-enzymatic synthesis and cell-growth inhibition activity of resveratrol analogues
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The stilbenoid resveratrol (1) was subjected to regioselective acetylation catalysed by Candida antarctica lipase (CAL) to obtain 4′- acetylresveratrol (2). CAL biocatalysed regioselective alcoholysis of 3,5,4′-triacetylresveratrol (3), 3,5,4′-tributanoylresveratrol (6), and 3, 4, 5′-trioctanoylresveratrol (9) afforded derivatives 4, 5, 7, 8, 10, and 11. Further resveratrol analogues (12-18) were obtained through methylation and hydrogenation reactions, whereas the 3,4,4′- trimethoxystilbene (19) was obtained by complete synthesis. Resveratrol and its lipophylic analogues were subjected to cell-growth inhibition bioassays towards DU-145 human prostate cancer cells. Compounds 2-19 showed cell-growth inhibition activity comparable to or higher than resveratrol (GI50 = 24.09 μM), displaying low or very low toxicity against non-tumorigenic human fibroblast cells. Comparison of the trimethoxy stilbenes 12 (GI50 = 2.92 μM) and 19 (GI50 = 25.39 μM) indicates that the position of the substituents is important for the activity. The marked activity of methyl ethers 12, 13, and 18 in comparison with that of the corresponding esters suggests that the different chemical reactivity, rather than steric factors, strongly influences the activity.
- Cardile, Venera,Lombardo, Laura,Spatafora, Carmela,Tringali, Corrado
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Read Online
- Remote meta-C–H Cyanation of Arenes Enabled by a Pyrimidine-Based Auxiliary
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An easily removable pyrimidine-based auxiliary has been employed for the remote meta-C?H cyanation of arenes. The scope of this Pd-catalyzed cyanation reaction using copper(I) cyanide as the cyanating agent was demonstrated with benzylsilanes, benzylsulfonates, benzylphophonates, phenethylsulfonates, and phenethyl ether derivatives. The method was utilized for the synthesis of pharmaceutically valuable precursors.
- Bag, Sukdev,Jayarajan, Ramasamy,Dutta, Uttam,Chowdhury, Rajdip,Mondal, Rahul,Maiti, Debabrata
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Read Online
- Visible-light-mediated phosphonylation reaction: formation of phosphonates from alkyl/arylhydrazines and trialkylphosphites using zinc phthalocyanine
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In this work, we developed a ligand- and base-free visible-light-mediated protocol for the photoredox syntheses of arylphosphonates and, for the first time, alkyl phosphonates. Zinc phthalocyanine-photocatalyzed Csp2-P and Csp3-P bond formations were efficiently achieved by reacting aryl/alkylhydrazines with trialkylphosphites in the presence of air serving as an abundant oxidant. The reaction conditions tolerated a wide variety of functional groups.
- Hosseini-Sarvari, Mona,Koohgard, Mehdi
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p. 5905 - 5911
(2021/07/12)
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- Selective hydrolysis of phosphorus(v) compounds to form organophosphorus monoacids
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An azide and transition metal-free method for the synthesis of elusive phosphonic, phosphinic, and phosphoric monoacids has been developed. Inert pentavalent P(v)-compounds (phosphonate, phosphinate, and phosphate) are activated by triflate anhydride (Tf2O)/pyridine system to form a highly reactive phosphoryl pyridinium intermediate that undergoes nucleophilic substitution with H2O to selectively deprotect one alkoxy group and form organophosphorus monoacids.
- Ash, Jeffrey,Cordero, Paula,Huang, Hai,Kang, Jun Yong
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p. 6007 - 6014
(2021/07/21)
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- Determination and application of the excited-state substituent constants of pyridyl and substituted phenyl groups
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Thirty six 1-pyridyl-2-arylethenes XCH=CHArY (abbreviated XAEY) were synthesized, in which, X is 2-pyridyl, 3-pyridyl and 4-pyridyl and Y is OMe, Me, H, Br, Cl, F, CF3, and CN. Their ultraviolet absorption spectra were measured in anhydrous ethanol, and their wavelengths of absorption maximum λmax were recorded. Also, the 234 λmax values of 1-substituted phenyl-2-arylethylene compounds (XAEY, where X is substituted phenyl) were collected. The excited-state substituent constants (Formula presented.) of three pyridyl groups and 23 substituted phenyl groups (total of 26) were obtained by means of curve-fitting method. Taking the λmax values of 358 samples of bi-arylethene derivatives as a data set and 126 samples of bi-aryl Schiff bases (including nine compounds synthesized by this work) as another data set, quantitative correlation analyses were performed by employing the obtained (Formula presented.) as a parameter, and good results were obtained for the two data sets. The reliability of the obtained (Formula presented.) values was verified. The results of this paper can provide excited-state substituent constants for the study and application of optical properties of conjugated organic compounds containing aryl groups.
- Cao, Chao-Tun,Yan, Lu,Cao, Chenzhong
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- Resveratrol A-cyclo-N(CH3)2-yl derivative as well as preparation method and application thereof
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The invention provides a resveratrol A-cyclo-N(CH3)2-yl derivative as well as a preparation method and application thereof, and belongs to the technical field of medicines. The invention provides theresveratrol A-cyclo-N(CH3)2-yl derivative with a structure shown in a formula I, which acts on an NHE-1 receptor as a sodium hydrogen exchange protein 1 (NHE-1) receptor antagonist in a targeting manner and simultaneously inhibits two signal transduction pathways, namely a phosphatidylinositol 3kinase/protein serine threonine kinase (PI3K/AKT) signal pathway and a Janus kinase/signal transductionand transcription activator (JAK/STAT); therefore, the effect of treating the alcoholic fatty liver is achieved.
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Paragraph 0079-0082
(2020/11/23)
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- Series of Compounds for Treatment of Skin Diseases and Other Conditions
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Compounds and methods related to the prevention and treatment of diseases and conditions, some of which are facilitated by melanogenesis are disclosed. Specifically, the present subject matter includes a series of compounds and compositions and their use for anti-melanogenic and antioxidant activity. This subject matter also includes the treatment of skin disorder due to acne vulgaris and related inflammatory and post inflammatory hyperpigmentation. Methods for synthesizing contemplated compounds are also disclosed.
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Paragraph 0107
(2020/05/02)
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- Discovery of boron-containing compounds as Aβ aggregation inhibitors and antioxidants for the treatment of Alzheimer's disease
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A novel series of boron-containing compounds were designed, synthesized and evaluated as multi-target-directed ligands against Alzheimer's disease. The biological activity results demonstrated that these compounds possessed a significant ability to inhibit self-induced Aβ aggregation (20.5-82.8%, 20 μM) and to act as potential antioxidants (oxygen radical absorbance capacity assay using fluorescein (ORAC-FL) values of 2.70-5.87). In particular, compound 17h is a potential lead compound for AD therapy (IC50 = 3.41 μM for self-induced Aβ aggregation; ORAC-FL value = 4.55). Compound 17h also functions as a metal chelator. These results indicated that boron-containing compounds could be new structural scaffolds for the treatment of AD.
- Lu, Chuan-Jun,Hu, Jinhui,Wang, Zechen,Xie, Shishun,Pan, Tingting,Huang, Ling,Li, Xingshu
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p. 1862 - 1870
(2018/11/24)
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- Direct Aryloxylation/Alkyloxylation of Dialkyl Phosphonates for the Synthesis of Mixed Phosphonates
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A strategy for the direct functionalization strategy of inertial dialkyl phosphonates with hydroxy compounds to afford diverse mixed phosphonates with good yields and functional-group tolerance has been developed. Mechanistic investigations involving both NMR studies and DFT studies suggest that an unprecedented highly reactive PV species (phosphoryl pyridin-1-ium salt), a key intermediate for this new synthetic transformation, is generated in situ from dialkyl phosphonate in the presence of Tf2O/pyridine.
- Huang, Hai,Denne, Johanna,Yang, Chou-Hsun,Wang, Haobin,Kang, Jun Yong
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p. 6624 - 6628
(2018/05/14)
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- Alcohol-based Michaelis-Arbuzov reaction: An efficient and environmentally-benign method for C-P(O) bond formation
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The famous Michaelis-Arbuzov reaction is extensively used both in the laboratory and industry to manufacture tons of widely-used organophosphoryl compounds every year. However, this method and the modified Michaelis-Arbuzov reactions developed recently still have some limitations. We now report a new alcohol-version of the Michaelis-Arbuzov reaction that can provide an efficient and environmentally-benign method to address the problems of the known Michaelis-Arbuzov reactions. That is, a wide range of alcohols can readily react with phosphites, phosphonites, and phosphinites to give all the three kinds of phosphoryl compounds (phosphonates, phosphinates, and phosphine oxides) using an n-Bu4NI-catalyzed efficient C-P(O) bond formation reaction. This general method can also be easily scaled up and used for further synthetic transformations in one pot.
- Ma, Xiantao,Xu, Qing,Li, Huan,Su, Chenliang,Yu, Lei,Zhang, Xu,Cao, Hongen,Han, Li-Biao
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supporting information
p. 3408 - 3413
(2018/08/06)
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- Activation of anti-oxidant Nrf2 signaling by substituted trans stilbenes
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Nrf2, which is a member of the cap'n’ collar family of transcription factors, is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. The importance of inflammation and oxidative stress in many chronic diseases supports the concept that activation of anti-oxidant Nrf2 signaling may have therapeutic potential. A number of Nrf2 activators have entered into clinical trials. Nrf2 exists in the cytosol in complex with its binding partner Keap1, which is a thiol-rich redox-sensing protein. In response to oxidative and electrophilic stress, select cysteine residues of Keap1 are modified, which locks Keap1 in the Nrf2-Keap1 complex and allows newly synthesized Nrf2 to enter the nucleus. Numerous Nrf2-activating chemicals, including a number of natural products, are electrophiles that modify Keap1, often by Michael addition, leading to activation of Nrf2. One concern with the design of Nrf2 activators that are electrophilic covalent modifiers of Keap1 is the issue of selectivity. In the present study, substituted trans stilbenes were identified as activators of Nrf2. These activators of Nrf2 are not highly electrophilic and therefore are unlikely to activate Nrf2 through covalent modification of Keap1. Dose-response studies demonstrated that a range of substituents on either ring of the trans stilbenes, especially fluorine and methoxy substituents, influenced not only the sensitivity to activation, reflected in EC50values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2. The stilbene backbone appears to be a privileged scaffold for development of a new class of Nrf2 activators.
- Deck, Lorraine M.,Whalen, Lisa J.,Hunsaker, Lucy A.,Royer, Robert E.,Vander Jagt, David L.
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p. 1423 - 1430
(2017/02/18)
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- Synthetic method for alkyl group phosphorous acid diester compounds or alkyl group phosphinic acid ester compounds
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The invention discloses a synthetic method for alkyl group phosphorous acid diester compounds or alkyl group phosphinic acid ester compounds. According to the synthetic method, alcohols which are cheap, easy to get, wide in source, stable and low in toxicity serve as alkylating reagents, iodine salt which is cheap and easy to get serves as catalysts, no solvent is needed, and the alkyl group phosphorous acid diester compounds can be selectively directly obtained after a reaction. The reaction method is simple, the condition is mild, no organic solvent is needed and operation is simple. According to the method, the requirements for reaction conditions are low, various types of alcohols such as a benzyl group type, an allyl type and a fat type can be utilized as the alkylate reagents to implement the synthesis of different types of substituted alkyl group phosphorous acid diester, and the method can be further expanded to the synthesis of the alkyl group phosphinic acid ester compounds through the reaction between the substituted phosphonous acid diester and the alcohols.
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Paragraph 0042; 0043; 0044; 0045
(2017/04/26)
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- Synthesis, biological evaluation and docking studies of trans-stilbene methylthio derivatives as cytochromes P450 family 1 inhibitors
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Cytochromes P450 family 1 (CYP1) are responsible for the metabolism of procarcinogens, for example polycyclic aromatic hydrocarbons and aromatic and heterocyclic amines. The inhibition of CYP1 activity is examined in terms of chemoprevention and cancer chemotherapy. We designed and synthesized a series of trans-stilbene derivatives possessing a combination of methoxy and methylthio functional groups attached in different positions to the trans-stilbene skeleton. We determined the effects of synthesized compounds on the activities of human recombinant CYP1A1, CYP1A2 and CYP1B1 and, to explain the variation of inhibitory potency of methoxystilbene derivatives and their methylthio analogues, we employed computational analysis. The compounds were docked to CYP1A1, CYP1A2 and CYP1B1 binding sites with the use of Accelrys Discovery Studio 4.0 by the CDOCKER procedure. For CYP1A2 and CYP1B1, values of scoring functions correlated well with inhibitory potency of stilbene derivatives. All compounds were relatively poor inhibitors of CYP1A2 that possess the most narrow and flat enzyme cavity among CYP1s. For the most active CYP1A1 inhibitor, 2-methoxy-4′-methylthio-trans-stilbene, a high number of molecular interactions was observed, although the interaction energies were not distinctive.
- Wierzchowski, Marcin,Dutkiewicz, Zbigniew,Gielara-Korzańska, Agnieszka,Korzański, Artur,Teubert, Anna,Te?yk, Artur,Stefański, Tomasz,Baer-Dubowska, Wanda,Mikstacka, Renata
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p. 1226 - 1236
(2017/10/06)
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- Novel preparation method of sulfonium salt derivatives with stilbene as conjugated system
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The invention provides a novel preparation method of sulfonium salt derivatives with stilbene as a conjugated system. The method comprises steps as follows: firstly, benzyl halides (Hal denotes halogen atom) substituted with different groups react with organic phosphate, a product reacts with benzaldehyde substituted with different sulfydryl under the alkaline condition, a high-yield disubstituted stilbene intermediate shown in (I)-a is prepared, and finally, the intermediate shown in (I)-a produces final sulfonium salt under the action of silver salt and alkyl halide or silver salt and alkyl acid ester; when different negative ions are required to be replaced, a salt exchange method is adopted to realize replacement. The provided scheme has the benefits, as examples but not confined, as follows: no noble metal catalyst is required, the raw materials are easy to obtain, and the cost is low; the reaction is performed at the room temperature, operation is simple and purification is convenient; favorable conditions are provided for large-scale industrial production of the sulfonium salt derivatives with stilbene as the conjugated system.
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Paragraph 0024-0025; 0027; 0033-0034; 0071-0073; 0076-0077
(2018/09/21)
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- Dehydrogenative Formation of Resorcinol Derivatives Using Pd/C-Ethylene Catalytic System
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The conversion of substituted 1,3-cyclohexanediones to the alkyl ethers of resorcinol using a Pd/C-ethylene system is reported. In these reactions, ethylene works as a hydrogen acceptor. The efficient synthesis of resveratrol was achieved using this protocol as a key step. In addition, the direct formation of substituted resorcinols was carried out by adding K2CO3 into the reaction media.
- El-Deeb, Ibrahim Yussif,Funakoshi, Tatsuya,Shimomoto, Yuya,Matsubara, Ryosuke,Hayashi, Masahiko
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p. 2630 - 2640
(2017/03/14)
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- Arylmethyl phosphonate preparation method
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The invention provides an arylmethyl phosphonate preparation method. The method includes the following steps that arylmethyl ester, triethyl phosphate and a catalyst are sequentially added into a reactor and reacted for 5-8 h at the temperature of 100-200 DEG C after full stirring, and after excessive triethyl phosphate is distilled off through decompression, the mixture continues to be reacted for 3-7 h at the temperature of 100-200 DEG C; then, the mixture is cooled to the room temperature, a product is extracted through a mixed solvent, and arylmethyl phosphonate is obtained after the mixed solvent is removed. The catalyst is one or more of tetramethyl ammonium bromide, tetraethylammonium bromide, tetrabutyl ammonium bromide, benzyltrimethyl ammonium bromide, cetyl trimethyl ammonium bromide, cetyltrimethyl ammonium chloride, ammonium chloride, sodium iodide and potassium iodide. Arylmethyl phosphonate is synthesized through a one-step method, other solvents are not added, operation is easy, and the product yield is high and can be 85.3% at maximum.
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Paragraph 0032; 0033
(2017/01/02)
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- TRIARYLAMINE DERIVATIVE AND ELECTROPHOTOGRAPHIC PHOTOSENSITIVE MEMBER
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A triarylamine derivative is represented by general formula (1) shown below. In general formula (1), R1, R2, and R3 each represent, independently of one another, a halogen atom, an optionally substituted alkyl group having a carbon number of at least 1 and no greater than 6, an optionally substituted alkoxy group having a carbon number of at least 1 and no greater than 6, or an optionally substituted aryl group having a carbon number of at least 6 and no greater than 12. In general formula (1), o, p, and q each represent, independently of one another, an integer of at least 0 and no greater than 4, and m and n each represent, independently of one another, an integer of at least 1 and no greater than 2.
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Paragraph 0088; 0089; 0090
(2016/06/28)
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- Resveratrol-Related Polymethoxystilbene Glycosides: Synthesis, Antiproliferative Activity, and Glycosidase Inhibition
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A small library of polymethoxystilbene glycosides (20-25) related to the natural polyphenol resveratrol have been synthesized and subjected, together with their aglycones 17-19, to an antiproliferative activity bioassay toward Caco-2 and SH-SY5Y cancer cells. Six of the compounds exhibit antiproliferative activity against at least one cell line. In particular, compounds 17 and 18 proved highly active on at least one of the two cell cultures. Compound 18 showed a GI50 value of 3 ΜM against Caco-2 cells, a value comparable to that of the anticancer drug 5-fluorouracil. The closely related compound 19 proved inactive, and its conjugates 22 and 25 showed weak cell growth inhibition. The results indicate that minimal differences in the structure of both polymethoxystilbenes and their glycosides can substantially affect the antiproliferative activity. The possible hydrolytic release of the aglycones 17-19 by β-glucosidase or β-galactosidase was also evaluated. Compounds 20-25 were also tested as potential β-glucosidase, β-galactosidase, and α-glucosidase inhibitors. A promising inhibitory activity toward α-glucosidase was observed for 21 (IC50 = 78 ΜM) and 25 (IC50 = 70 ΜM), which might be indicative of their potential as lead compounds for development of antidiabetic or antiobesity agents.
- Cardullo, Nunzio,Spatafora, Carmela,Musso, Nicolò,Barresi, Vincenza,Condorelli, Daniele,Tringali, Corrado
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p. 2675 - 2683
(2015/12/09)
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- THERAPEUTIC AGENTS FOR SKIN DISEASES AND CONDITIONS
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The present invention relates to method(s) of treating a subject afflicted with a skin disease or condition, the method comprising administering to the subject or patient in need a composition comprising a therapeutically effective amount of a substituted cis or trans- stilbene or a stilbene hybrid. A method of treating or reducing the likelihood of a skin disease or condition in a patient is an additional embodiment of the present invention. Preferred pharmaceutical compositions of the invention include nanoemulsions comprising a therapeutically effective amount of a substituted cis or trans-stilbene or stilbene hybrid and at least one antibiotic.
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Page/Page column 36; 48-49
(2015/06/18)
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- Synthesis and bioactivity of resveratrol analogues
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It has been reported that resveratrol enhanced SIRT1 expression and significantly mimicked calorie restriction by stimulating Sir2 which is the most homologic homologue of SIRT1 of mammalian. A series of novel resveratrol derivatives were designed and synthesized as novel SIRT1 activator candidates. These synthesized compounds were characterized by spectral (1H NMR) analysis and examined for their Sir2 activation against yeast parental strain-BY4743 at a concentration of 100 μM/L by Bioscreen C MBR machine. Several compounds showed a promising Sir2 activation activity compared with resveratrol. Meanwhile, the structure-activity relationships with Sirt2 activation activities were also discussed.
- Ao, Junli,Chen, Yuanmou,Xu, Xiaoling,Zhang, Xu,Yu, Yue,Yu, Peng,Hua, Erbing
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p. 2092 - 2098
(2014/06/09)
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- Reductive coupling reactions: A new strategy for C(sp3)-P bond formation
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The C(sp3)-P bond forming reaction utilizing N-tosylhydrazones as readily available alkylating reagents was developed, which provides a new opportunity for preparing phosphine oxide derivatives with moderate to good yields. This reductive coupling reaction is proposed to proceed through an insertion of copper carbene into P-H bond of H-phosphorus oxides. The salient features of the reaction are operational simplicity and functional-group tolerance.
- Chen, Zi-Sheng,Zhou, Zhao-Zhao,Hua, Hui-Liang,Duan, Xin-Hua,Luo, Jian-Yi,Wang, Jia,Zhou, Ping-Xin,Liang, Yong-Min
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p. 1065 - 1068
(2013/02/25)
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- Design, synthesis and structure-activity relationships of some novel, highly potent anti-invasive (E)- and (Z)-stilbenes
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In our ongoing exploration of the structure-activity landscape of anti-invasive chalcones, we have prepared and evaluated a number of structurally related (E)- and (Z)-stilbenes. These molecules exhibited an extraordinary high in vitro potency in the chick heart invasion assay, being active up to 10 nmol L-1, a concentration level a 100-fold lower than the lowest effective doses that have been reported for natural analogues. Furthermore, they possess an interesting pharmacological profile in silico.
- Roman, Bart I.,De Coen, Laurens M.,Mortier, Séverine Thérèse F.C.,De Ryck, Tine,Vanhoecke, Barbara W.A.,Katritzky, Alan R.,Bracke, Marc E.,Stevens, Christian V.
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p. 5054 - 5063
(2013/09/02)
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- Copper-catalyzed synthesis of alkylphosphonates from H-phosphonates and N-tosylhydrazones
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A new catalytic system for the alkylation of H-phosphonates and diphenylphosphine oxide with N-tosylhydrazones has been developed. In the presence of copper(I) iodide and base, H-phosphonates react with N-tosylhydrazones to afford the corresponding coupled alkylphosphonates in good to excellent yields without any ligands. Alkylphosphonates can also be prepared in a one-pot process directly from carbonyl compounds without the isolation of tosylhydrazone intermediates.
- Miao, Wenjun,Gao, Yuzhen,Li, Xueqin,Gao, Yuxing,Tang, Guo,Zhao, Yufen
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p. 2659 - 2664
(2013/01/15)
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- Synthesis of α-arylphosphonates using copper-catalyzed α-arylation and deacylative α-arylation of β-ketophosphonates
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Efficient methods for the direct arylation and deacylative arylation of β-ketophosphonates with iodoarenes in presence of a copper(I) or a copper(II) salt as the catalysts have been developed. The corresponding α-arylphosphonates were obtained in high yields. A tentative mechanism for the deacylative arylation reaction was proposed on the basis of the experimental data. Copyright
- Rout, Laxmidhar,Regati, Sridhar,Zhao, Cong-Gui
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scheme or table
p. 3340 - 3346
(2012/01/17)
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- New hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcription
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We have synthesized a series of new (E) stilbenoid derivatives containing hydroxy groups at ring positions identical or similar to those of trans-resveratrol and bearing one or two bulky electron donating groups ortho to 4′-OH and we have evaluated their neuroprotective activity using glutamate-challenged HT22 hippocampal neurons to model oxidative stress-induced neuronal cell death. The most active derivatives, 5-{(E)-2-[3,5-bis(1- ethylpropyl)-4-hydroxyphenyl]ethenyl}-1,3-benzenediol (2), 5-[(E)-2-(3,5-di- tert-butyl-4-hydroxyphenylethenyl)]-1,3-benzenediol (4) and 5-{(1E,3E)-4-[3,5- bis(1-ethylpropyl)-4-hydroxyphenyl]-1,3-butadienyl}-1,3-benzenediol (6), had EC50 values of 30, 45 and 12 nM, respectively, and were ca. 100 to 400-fold more potent than resveratrol. Derivatives 2, 4 and 6 lacked cytotoxic activity against HT22 cells and estrogen receptor agonist or antagonist activity in estrogen response element-dependent gene expression and in estrogen-dependent proliferation of MCF-7 human breast cancer cells. In addition, they were incapable of interfering with aryl hydrocarbon receptor-mediated xenobiotic response element-dependent gene expression. Derivatives 2, 4 and 6 might assist in the development of lead candidates against oxidative stress-driven neurodegenerative diseases that will not increase endocrine cancer risk nor affect drug activation and detoxification mechanisms.
- Villalonga-Barber, Carolina,Meligova, Aggeliki K.,Alexi, Xanthippi,Steele, Barry R.,Kouzinos, Constantinos E.,Screttas, Constantinos G.,Katsanou, Efrosini S.,Micha-Screttas, Maria,Alexis, Michael N.
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supporting information; scheme or table
p. 339 - 351
(2011/02/27)
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- Direct conversion of benzylic and allylic alcohols to phosphonates
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Benzyl phosphonate esters often serve as reagents in Horner-Wadsworth- Emmons reactions. In most cases, they can be prepared from benzylic alcohols via formation of the corresponding halide followed by an Arbuzov reaction. To identify a more direct synthesis of phosphonate esters, we have developed a one-flask procedure for conversion of benzylic and allylic alcohols to the corresponding phosphonates through treatment with triethyl phosphite and ZnI2.
- Barney, Rocky J.,Richardson, Rebekah M.,Wiemer, David F.
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supporting information; experimental part
p. 2875 - 2879
(2011/05/19)
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- 3,4,4′-Trihydroxy-trans-stilbene, an analogue of resveratrol, is a potent antioxidant and cytotoxic agent
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Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a naturally occurring polyphenol widely distributed in food and dietary plants. This phytochemical has been intensively studied as an efficient antioxidant and anticancer agent, and a variety of substituted stilbenes have been developed in order to improve the potency of resveratrol. In this work, we described the synthesis of 3,4,4-trihydroxy-trans-stilbene (3,4,4′-THS), an analogue of resveratrol, and studied its antioxidant and cytotoxic activity in vitro. 3,4,4-THS was much more efficient than resveratrol in protecting against free radical-induced lipid peroxidation, photo-sensitized DNA oxidative damage, and free radical-induced hemolysis of human red blood cells. More potent growth inhibition in cultured human leukemia cells (HL-60) was also observed for 3,4,4-THS. The relationship between the antioxidant efficiency and cytotoxic activity was discussed, with the emphasis on inhibition of the free radical enzyme ribonucleotide reductase by antioxidants. The result that this subtle structure modification of resveratrol drastically improves its bioactivity provides important strategy to develop novel resveratrol-based molecules.
- Cai, Wenqing,Zhang, Liangwei,Song, Yanlin,Zhang, Baoxin,Cui, Xuemei,Hu, Guanming,Fang, Jianguo
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experimental part
p. 1379 - 1387
(2012/07/31)
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- Synthesis, UV/vis spectra and electrochemical characterisation of arylthio and styryl substituted ferrocenes
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Two series of substituted ferrocenes were synthesised using either the Horner-Wadswor th-Emmons reaction or monolithiation of ferrocene. The series consist of arylthio- and styryl-ferrocenes with different substituents in the para position of the aryl rings of the systems. The electronic communication was investigated by comparing the substituent effects in absorption spectroscopy and in cyclic voltammetry. A small substituent effect was found in the electronic transitions of the styryl substituted ferrocenes. The oxidation of the ferrocene derivatives showed clear substituent effects as illustrated by the linear Hammett plots. The effect was shown to be an order of magnitude larger in the arylthio-systems than in the styryl systems. It is suggested that the reason behind the large effect is a direct sulfur-iron orbital overlap. Versita Sp. z o.o.
- Sorensen, Thomas J.,Nielsen, Merete F.
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experimental part
p. 610 - 618
(2012/04/10)
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- Preparation of benzylphosphonates via a palladium(0)-catalyzed cross-coupling of H-phosphonate diesters with benzyl halides. Synthetic and mechanistic studies
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We have developed a new, efficient method for the synthesis of benzylphosphonate and benzylphosphonothioate diesters via a palladium(0)- catalyzed cross-coupling reaction between benzyl halides and H-phosphonate or H-phosphonothioate diesters, using Pd2(dba)3(CHCl 3) as a palladium source and Xantphos as a supporting ligand. Some mechanistic aspects of these reactions were investigated using 31P NMR spectroscopy.
- Laven, Gaston,Kalek, Marcin,Jezowska, Martina,Stawinski, Jacek
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experimental part
p. 967 - 975
(2010/08/04)
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- Hybrid-increased radical-scavenging activity of resveratrol derivatives by incorporating a chroman moiety of vitamin e
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A winning combination: Resveratrol derivatives incorporating a chroman moiety of vitaminE were constructed, resulting in the remarkable enhancement in tris(2,4,6-trichloro-3,5-dinitrophenyl)methyl radical (HNTTM)-scavenging activity as compared with the parent molecules (see scheme). Reaction kinetic analysis, oxidative product identification, and redox potential determination demonstrate that the reaction is governed by a sequential proton-loss electron-transfer (SPLET) mechanism.
- Yang, Jie,Liu, Guo-Yun,Lu, Dong-Liang,Dai, Fang,Qian, Yi-Ping,Jin, Xiao-Ling,Zhou, Bo
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supporting information; experimental part
p. 12808 - 12813
(2011/02/22)
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- Synthesis and evaluation of stilbene derivatives as a potential imaging agent of amyloid plaques
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Fluorescence probes that can detect Aβ (β-amyloid peptide) plaque are important tools for diagnosis of Alzheimer's disease (AD), and 4-N-methylamino-4′-hydroxystilbene (SB-13) is one of the promising candidate molecules. We report here the synthesis of SB-13 derivatives that consist of various electron donating/withdrawing moieties and distinct size of N-substituents. The synthesized compounds were screened for detection of Aβ40 fibrils in vitro. Four compounds exhibited more than sixfold intensity increase, and they were further analyzed for detail bindings and Aβ plaque imaging. Among these molecules, compound 42 meets two critical requirements for imaging agent; high fluorescence responsiveness and strong binding affinity. This compound showed more than 25-fold increase with the dissociation constant of 1.13 ± 0.37 μM. In AD mouse brain tissue, 42 selectively stained Aβ plaque, more specifically peripheral regions of Aβ plaque. This finding demonstrated its potential use as brain-imaging agents for AD studies.
- Hong, Myeng Chan,Kim, Yun Kyung,Choi, Jae Yong,Yang, Si Qiang,Rhee, Hakjune,Ryu, Young Hoon,Choi, Tae Hyun,Cheon, Gi Jeong,An, Gwang Il,Kim, Hye Yun,Kim, Youngsoo,Kim, Dong Jin,Lee, Jun-Seok,Chang, Young-Tae,Lee, Kyo Chul
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experimental part
p. 7724 - 7730
(2011/01/13)
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- Hydroxylated Long-Chain Resveratrol Derivatives Useful as Neurotrophic Agents
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The present invention relates to a compound of general formula (I) below in which R1, R2 and R3 represent, independently of one another, a hydrogen atom or a C1-C6 alkyl group or a (C1-C6 alkyl)carbonyl group, R4, R5, R6 and R7 represent a hydrogen or a C1-C6 alkyl group, a C1-C6 alkoxy group or a (C1-C6 alkyl)carbonyloxy group, and n is an integer between 8 and 20, or its pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers, and also mixtures thereof. The invention also relates to a pharmaceutical composition comprising the compound and to the use thereof as a neurotrophic agent.
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Page/Page column 12-13
(2010/03/31)
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- Rh-catalyzed Negishi alkyl-aryl cross-coupling leading to α- or β-phosphoryl-substituted alkylarenes
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The catalytic cross-coupling between ArZnX and ICH2(CH 2)nP(O)(OEt)2 (n = 0-3) has been investigated to determine the utility of the Rh catalyst during the alkyl-aryl cross-coupling and to develop a new syntheti
- Takahashi, Hideki,Inagaki, Shinya,Yoshii, Naoko,Gao, Fuxing,Nishihara, Yasushi,Takagi, Kentaro
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supporting information; experimental part
p. 2794 - 2797
(2009/09/08)
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- Palladium(0)-catalyzed benzylation of H-phosphonate diesters: An efficient entry to benzylphosphonates
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A new, efficient method for the synthesis of benzylphosphonate diesters via a palladium(0)-catalyzed cross-coupling reaction between benzyl halides and H-phosphonate diesters, using Pd(OAc)2 as a palladium source and Xantphos as a supporting ligand, has been developed. Georg Thieme Verlag Stuttgart.
- Lavén, Gaston,Stawinski, Jacek
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scheme or table
p. 225 - 228
(2009/05/30)
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- On the functionalization of [2.2](1,4)phenanthrenoparacyclophane
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Two routes for preparing functionalized [2.2](1,4) phenanthrenoparacyclophanes are described: either the parent system 2 is subjected to electrophilic substitution (bromination, Friedel-Crafts acylation, Rieche formylation: preparation of 5, 6, 7, 11 and 12) or the desired substituents are incorporated in the early stages of the synthesis by the preparation of the corresponding functionalized styryl paracyclophanes and their photocyclization to the respective phenanthrenocyclophanes. By these specific routes various bronudes (22a,b), ethers (28a-c) and phenols (29a,b) were synthesized. The latter derivatives, on oxidation, furnish para-(31) and ortho-quinonophanes (30, 32, 33), useful substrates for the preparation of cyclophanes containing phenazine subunits (36). The stilbene → phenanthrene photocyclization can also be employed for the preparation of benzothiophenophanes, e.g. 43 and 44, from the respective precursors. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Hopf, Henning,Hucker, Joachim,Ernst, Ludger
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p. 1891 - 1904
(2008/02/06)
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- Engineered chimeric enzymes as tools for drug discovery: Generating reliable bacterial screens for the detection, discovery, and assessment of estrogen receptor modulators
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Engineered protein-based sensors of ligand binding have emerged as attractive tools for the discovery of therapeutic compounds through simple screening systems. We have previously shown that engineered chimeric enzymes, which combine the ligand-binding domains of nuclear hormone receptors with a highly sensitive thymidylate synthase reporter, yield simple sensors that report the presence of hormone-like compounds through changes in bacterial growth. This work describes an optimized estrogen sensor in Escherichia coli with extraordinary reliability in identifying diverse estrogenic compounds and in differentiating between their agonistic/antagonistic pharmacological effects. The ability of this system to assist the discovery of new estrogen-mimicking compounds was validated by screening a small compound library, which led to the identification of two structurally novel estrogen receptor modulators and the accurate prediction of their agonistic/antagonistic biocharacter in human cells. Strong evidence is presented here that the ability of our sensor to detect ligand binding and recognize pharmacologically critical properties arises from allosteric communication between the artificially combined protein domains, where different ligand-induced conformational changes in the receptor are transmitted to the catalytic domain and translated to distinct levels of enzymic efficiency. To the best of our knowledge, this is one of the first examples of an engineered enzyme with the ability to sense multiple receptor conformations and to be either activated or inactivated depending on the nature of the bound effector molecule. Because the proposed mechanism of ligand dependence is not specific to nuclear hormone receptors, we anticipate that our protein engineering strategy will be applicable to the construction of simple sensors for different classes of (therapeutic) binding proteins.
- Skretas, Georgios,Meligova, Aggeliki K.,Villalonga-Barber, Carolina,Mitsiou, Dimitra J.,Alexis, Michael N.,Micha-Screttas, Maria,Steele, Barry R.,Screttas, Constantinos G.,Wood, David W.
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p. 8443 - 8457
(2008/02/09)
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- Dual bioactivity of resveratrol fatty alcohols: Differentiation of neural stem cells and modulation of neuroinflammation
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The synthesis of resveratrol fatty alcohols (RFAs), a new class of small molecules presenting strong potential for the treatment of neurological diseases, is described. RFAs, hybrid compounds combining the resveratrol nucleus and ω-alkanol side chains, are able to modulate neuroinflammation and to induce differentiation of neural stem cells into mature neurons. Acting on neuroprotection and neuroregeneration, RFAs represent an innovative approach for the treatment or cure of neuropathies.
- Hauss, Frederique,Liu, Jiawei,Michelucci, Alessandro,Coowar, Djalil,Morga, Eleonora,Heuschling, Paul,Luu, Bang
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p. 4218 - 4222
(2008/02/10)
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- Concise strategy to the core structure of the macrolide queenslandon
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(Diagram presented) The fully functionalized core structure of the macrolactone queenslandon was prepared using a novel strategy consisting of a glycolate aldol reaction and hydroboration of the derived enol ether 17 followed by Suzuki cross-coupling with an iodostyrene. After conversion of the cross-coupling product to the seco acid 22, Mitsunobu macrolactonization and protecting group manipulations led to the queenslandon model 5.
- Khartulyari, Anton S.,Kapur, Manmohan,Maier, Martin E.
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p. 5833 - 5836
(2007/10/03)
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- Substituted trans-stilbenes, including analogues of the natural product resveratrol, inhibit the human tumor necrosis factor alpha-induced activation of transcription factor nuclear factor kappaB
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The transcription factor nuclear factor kappaB (NF-κB), which regulates expression of numerous antiinflammatory genes as well as genes that promote development of the prosurvival, antiapoptotic state is up-regulated in many cancer cells. The natural product resveratrol, a polyphenolic trans-stilbene, has numerous biological activities and is a known inhibitor of activation of NF-κB, which may account for some of its biological activities. Resveratrol exhibits activity against a wide variety of cancer cells and has demonstrated activity as a cancer chemopreventive against all stages, i.e., initiation, promotion, and progression. The biological activities of resveratrol are often ascribed to its antioxidant activity. Both antioxidant activity and biological activities of analogues of resveratrol depend upon the number and location of the hydroxy groups. In the present study, phenolic analogues of resveratrol and a series of substituted trans-stilbenes without hydroxy groups were compared with resveratrol for their abilities to inhibit the human tumor necrosis factor alpha-induced (TNF-α) activation of NF-κB, using the Panomics NF-κB stable reporter cell line 293/NF-κB-luc. A series of 75 compounds was screened to identify substituted trans-stilbenes that were more active than resveratrol. Dose-response studies of the most active compounds were carried out to obtain IC50 values. Numerous compounds were identified that were more active than resveratrol, including compounds that were devoid of hydroxy groups and were 100-fold more potent than resveratrol. The substituted trans-stilbenes that were potent inhibitors of the activation of NFκB generally did not exhibit antioxidant activity. The results from screening were confirmed using BV-2 microglial cells where resveratrol and analogues were shown to inhibit LPS-induced COX-2 expression.
- Heynekamp, Justin J.,Weber, Waylon M.,Hunsaker, Lucy A.,Gonzales, Amanda M.,Orlando, Robert A.,Deck, Lorraine M.,Vander Jagt, David L.
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p. 7182 - 7189
(2007/10/03)
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- Synthesis and anti-inflammatory activity of resveratrol analogs
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Seventeen novel resveratrol derivatives were synthesized. Their anti-inflammatory activities were tested on xylene-induced mouse ear edema. The pharmacological results showed that some compounds have potent anti-inflammatory activities.
- Chen, Guoliang,Shan, Wei,Wu, Yingliang,Ren, Lixiang,Dong, Jinhua,Ji, Zhizhong
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p. 1587 - 1590
(2007/10/03)
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- CCR5 antagonists as anti-HIV-1 agents. Part 3: Synthesis and biological evaluation of piperidine-4-carboxamide derivatives
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Replacement of the 5-oxopyrrolidin-3-yl fragment in the previously reported lead structure with a 1-acetylpiperidin-4-yl group led to the discovery of a novel series of potent CCR5 antagonists. Introduction of small hydrophobic substituents on the central phenyl ring increased the binding affinity, providing low to sub-nanomolar CCR5 antagonists. The selected compound 11f showed excellent antiviral activity against CCR5-using HIV-1 replication in human peripheral blood mononuclear cells (EC50 = 0.59 nM) and an acceptable pharmacokinetic profile in dogs.
- Imamura, Shinichi,Nishikawa, Youichi,Ichikawa, Takashi,Hattori, Taeko,Matsushita, Yoshihiro,Hashiguchi, Shohei,Kanzaki, Naoyuki,Iizawa, Yuji,Baba, Masanori,Sugihara, Yoshihiro
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p. 397 - 416
(2007/10/03)
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- Synthesis, antitumor evaluation, and apoptosis-inducing activity of hydroxylated (E)-stilbenes
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The parallel solution-phase synthesis of a series of 30 monohydroxylated (E)-stilbene analogues is described. In vitro screening revealed low micromolar activity (GI50) against the MDA MB 468 breast cancer cell line. Activity in MDA MB 468 cells correlated with the ability to induce apoptosis following drug treatment by the most potent agents in the series, e.g., 5dy and 5jy, an observation further reinforced by Annexin V-FITC analysis and fluorescence microscopy.
- Lion, Cedric J.,Matthews, Charles S.,Stevens, Malcolm F. G.,Westwell, Andrew D.
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p. 1292 - 1295
(2007/10/03)
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- Resveratrol analogues as selective cyclooxygenase-2 inhibitors: Synthesis and structure-activity relationship
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A series of hydroxylated and methoxylated trans-stilbenes were synthesized and evaluated for their ability to inhibit COX-1 and COX-2. Some of the hydroxylated derivatives are highly selective COX-2 inhibitor with potency comparable or better than clinically established drugs. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is found in grapes and various medical plants. Among cytotoxic, antifungal, antibacterial cardioprotective activity resveratrol also demonstrates non-selective cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibition. In order to find more selective COX-2 inhibitors a series of methoxylated and hydroxylated resveratrol derivatives were synthesized and evaluated for their ability to inhibit both enzymes using in vitro inhibition assays for COX-1 and COX-2 by measuring PGE2 production. Hydroxylated but not methoxylated resveratrol derivatives showed a high rate of inhibition. The most potent resveratrol compounds were 3,3′,4′,5-tetra-trans-hydroxystilbene (COX-1: IC50 = 4.713, COX-2: IC50 = 0.0113 μM, selectivity index = 417.08) and 3,3′,4,4′,5,5′-hexa-hydroxy-trans-stilbene (COX-1: IC 50 = 0.748, COX-2: IC50 = 0.00104 μM, selectivity index = 719.23). Their selectivity index was in part higher than celecoxib, a selective COX-2 inhibitor already established on the market (COX-1: IC 50 = 19.026, COX-2: IC50 = 0.03482 μM, selectivity index = 546.41). Effect of structural parameters on COX-2 inhibition was evaluated by quantitative structure-activity relationship (QSAR) analysis and a high correlation was found with the topological surface area TPSA (r = 0.93). Docking studies on both COX-1 and COX-2 protein structures also revealed that hydroxylated but not methoxylated resveratrol analogues are able to bind to the previously identified binding sites of the enzymes. Hydroxylated resveratrol analogues therefore represent a novel class of highly selective COX-2 inhibitors and promising candidates for in vivo studies.
- Murias, Marek,Handler, Norbert,Erker, Thomas,Pleban, Karin,Ecker, Gerhard,Saiko, Philipp,Szekeres, Thomas,J?ger, Walter
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p. 5571 - 5578
(2007/10/03)
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- A convenient method for the synthesis of electron-rich phosphonates
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Very electron-rich benzylic-type phosphonates can be prepared by treating the corresponding alcohols in triethyl phosphite with one equivalent of iodine at an appropriate temperature in a general one-pot process.
- Zheng, Shijun,Barlow, Stephen,Parker, Timothy C.,Marder, Seth R.
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p. 7989 - 7992
(2007/10/03)
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- Syntheses of the stereoisomers of neolignans morinol C and D
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Morinol C and morinol D are neolignans isolated from the Chinese medicinal herb Morina chinensis as racemates. (1R,2R)-Morinol C and (1S,2R)-morinol D were synthesized from (+)-(3R,4R)-4-(3,4-dimethoxyphenyl)-3-pivaloyloxymethyl-4-butanolide 4. On the other hand, (1S,2S)-morinol C and (1R,2S)-morinol D were synthesized from anti-aldol product 8.
- Yamauchi, Satoshi,Uno, Hidemitsu
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p. 1323 - 1329
(2007/10/03)
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- A practical synthesis of trans-resveratrol
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The total synthesis of biologically active substance transresveratrol 1 has been described with moderate overall yield (35.7%). Starting from 3,5-dihydroxybenzoic acid, 3,5-dimethoxybenzonate methyl ester is prepared. The reaction of the ester with hydrazine hydrate followed by oxidation with K3[Fe(CN)6] gives the key intermediate 3,5-dimethoxy-benzaldehyde, which is condensed with diethyl(4-methoxy-benzyl)phosphonate to yield only trans-3,5,4′-trimethylstilbene. The synthesis of trans-resveratrol is completed by the deprotection reaction with BBr3/CH2Cl2.
- Shen, Zhen Lu,Zhuo, Guang Lan,Jiang, Xuan Zhen
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p. 2395 - 2398
(2007/10/03)
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- Evaluation of resveratrol derivatives as potential antioxidants and identification of a reaction product of resveratrol and 2,2-diphenyl-1- picryhydrazyl radical
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Resveratrol (3,4',5-trihydroxy-trans-stilbene), an antioxidant from grapes, and five other polyhydroxystilbenes were synthesized. Their antioxidative properties were evaluated in two model systems [pure lipid oxidation using the Rancimat method and 2,2-diphenyl-1-picryhydrazyl (DPPH) free radical scavenging model.] 3,3',4,5'-Tetrahydroxystilbene, 3,3',4,5,5'- pentahydroxystilbene, and 3,4,4',5-tetrahydroxystilbene were found to be more active than resveratrol in both models. A dimer of resveratrol was identified as the major radical reaction product when resveratrol was reacted with DPPH radicals.
- Wang, Mingfu,Jin, Yi,Ho, Chi-Tang
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p. 3974 - 3977
(2007/10/03)
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