- A fast and convenient heck reaction in water under microwave irradiation
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A fast and convenient base-free Heck reaction of acrylic acid and allyl alcohol with hypervalent iodonium salts was achieved under microwave irradiation in water, providing a simple method for synthesis of trans-cinnamic acids and trans-cinnamyl alcohols in good yields in short time. Georg Thieme Verlag Stuttgart.
- Zhu, Min,Song, Yunlong,Cao, Yan
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- Alum-Cs2CO3 as a new recyclable solid base catalyst for the efficient syntheses of arylidenemalononitriles, esters and arylcinnamic acids in water
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The condensation between aromatic aldehydes and malononitrile, ethylcyanoacetate and malonic acid for the syntheses of arylidenemalononitriles, arylidenemalonic acid esters and aryl cinnamic acids in water using alum-Cs2CO3 as a solid support catalyst has been described. Alum-Cs2CO3 was found to be a highly active, stable and recyclable catalyst under reaction conditions.
- Taduri, Ashok Kumar,Devi, B. Rama
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- FTIR studies of hydrogen bonding between α, β-usaturated esters and alcohols
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The enthalpy (and entropy) of hydrogen bond formation has been measured between the ester carbonyl groups of the two α, β-unsaturated esters thienylacryloyl (TAOMe) and 5-methylthienylacryloyl (5MeTAOMe) methyl ester and the hydrogen bond donors ethanol, phenol and 3,5-dichlorophenol in CCl4. For the esters, the hydrogen bonding strengths were measured by quantitating the amount of bound and unbound donor, using the O-H stretching region, as a function of temperature and applying the van't Hoff equation. The decrease in vC=O of the ester carbonyl group upon hydrogen bond formation (ΔvC=O) has also been measured and correlated with the enthalpy of hydrogen bond formation. A linear correlation is observed between the enthalpy of hydrogen bond formation -ΔH and ΔvC=O, with -ΔH = 1.36ΔvC=O - 16.1, where ΔH is measured in kJ mol-1 and Δv in cm-1. Comparison with data for other carbonyl acceptor compounds indicates that the carbonyl group of the above α, β-unsaturated esters is more readily polarized than the carbonyl group of saturated esters or ketones. The quantitative relationship between -ΔH and ΔvC=O derived here has been used to determine the change in the enthalpy of hydrogen bond formation between substrate and enzyme groups in a series of acylserine proteases.
- Tonge,Fausto,Carey
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- A PdCl2-ionic liquid brush assembly: An efficient and reusable catalyst for Mizoroki-Heck reaction in neat water
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An efficient and reusable heterogeneous catalytic assembly of PdCl 2 held in ionic liquid brushes has been synthesized and an environmentally-friendly procedure was developed for coupling aryl iodides with acrylic acid. These reactions were conducted in water under aerobic conditions with water-insoluble or even solid aryl iodides and they proceeded smoothly and cleanly without any organic co-solvent or other additives. A 0.5 mol% (based on Pd atom) dose of the catalyst was found to be sufficient for Mizoroki-Heck reaction. The catalyst is easily recovered post reaction, via simple filtration, and reused at least eight times without a noticeable loss of activity. The protocol has the advantages of excellent yield, environmental friendliness, and catalyst recyclability. Copyright
- Shi, Xianying,Han, Xiaoyan,Ma, Wenjuan,Fan, Juan,Wei, Junfa
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- Pd nanoparticles encaged in nanoporous interpenetrating polymer networks: A robust recyclable catalyst for Heck reactions
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A novel type of Heck reaction catalyst composed of hydrophilic interpenetrating polymer networks (IPNs) and palladium (Pd) nanoparticles was prepared by simultaneous crosslinking of polyvinyl alcohol and polyacrylamide. The mesh sizes of the IPNs are one order of magnitude smaller than the average sizes of the uniformly dispersed Pd nanoparticles, which functions well to stabilize Pd nanoparticles and prevent aggregation. The Pd particles in the IPNs can catalyze Heck coupling reactions with high activities and be recycled over 20 times, providing more sustainability than any other polymer-stabilized Pd catalyst reported in the literature. The confined reactions inside the IPN nanopores in neat water may provide a green route for C-C coupling reactions.
- Zhan, Kan,You, Huanhuan,Liu, Wenyu,Lu, Jie,Lu, Ping,Dong, Jian
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- Heck reaction in water with amphiphilic resin-supported palladium-phosphine complexes
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The Heck reaction of various aryl halides and alkenes took place in water in the presence of an amphiphilic polystyrene-poly(ethylene glycol) resin-supported palladium-phosphine complex to give the corresponding styrene derivatives in quantitative yields.
- Uozumi, Yasuhiro,Kimura, Tsutomu
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- Hydroxyapatite supported caesium carbonate as a new recyclable solid base catalyst for the Knoevenagel condensation in water
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The Knoevenagel condensation between aromatic aldehydes and malononitrile, ethyl cyanoacetate or malonic acid with hydroxyapatite supported caesium carbonate in water is described. HAP-Cs2CO3 was found to be a highly active, stable and recyclable catalyst under the reaction conditions.
- Gupta, Monika,Gupta, Rajive,Anand, Medha
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- Discovery of Novel Benzothiazepinones as Irreversible Covalent Glycogen Synthase Kinase 3β Inhibitors for the Treatment of Acute Promyelocytic Leukemia
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Recently, irreversible inhibitors have attracted great interest in antitumors due to their advantages of forming covalent bonds to target proteins. Herein, some benzothiazepinone compounds (BTZs) have been designed and synthesized as novel covalent GSK-3β inhibitors with high selectivity for the kinase panel. The irreversible covalent binding mode was identified by kinetics and mass spectrometry, and the main labeled residue was confirmed to be the unique Cys14 that exists only in GSK-3β. The candidate 4-3 (IC50 = 6.6 μM) showed good proliferation inhibition and apoptosis-inducing ability to leukemia cell lines, low cytotoxicity on normal cell lines, and no hERG inhibition, which hinted the potential efficacy and safety. Furthermore, 4-3 exhibited decent pharmacokinetic properties in vivo and remarkably inhibited tumor growth in the acute promyelocytic leukemia (APL) mouse model. All the results suggest that these newly irreversible BTZ compounds might be useful in the treatment of cancer such as APL.
- Zhang, Peng,Min, Zhihui,Gao, Yang,Bian, Jiang,Lin, Xin,He, Jie,Ye, Deyong,Li, Yilin,Peng, Chao,Cheng, Yunfeng,Chu, Yong
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- Synthesis of heteroleptic pentavalent antimonials bearing heterocyclic cinnamate moieties and their biological studies
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In the search of new drugs with high therapeutic efficacy, antimony (V) dicarboxylates bearing cinnamate moieties with general formula [SbR3(O2CR′)2] have been synthesized and characterized by spectroscopic techniques like FTIR, multinuclear (1H and 13C) NMR and single crystal X-ray diffraction. The organic moieties (R) in the complexes are phenyl and p-tolyl while the carboxylates are heterocyclic acrylates. In the crystal structure of [Sb(phenyl)3(O2CC2H2C4H3O)2] (1), [Sb(phenyl)3(O2CC2H2C4H3S)2] (3), [Sb(p-tolyl)3(O2CC2H2C4H3S)2] (5) and [Sb(p-tolyl)3(O2CC2H2C4H2O(CH3))2] (6), antimony was found to adopt a distorted trigonal bipyramidal geometry and was monomeric with phenyl or p-tolyl groups at equatorial and carboxylate ligands at axial positions. Furthermore, biological activities of carboxylates and their corresponding complexes were conducted including antileishmanial activity (against Leishmania tropica KWH23 parasite), anticancer (against HepG2 cell line), antibacterial (against Staphylococcus aureus, E. coli, P. aeruginosa and K. pneumoniae) and α-amylase inhibition potentials. Results show that compounds (4), (5) and (6) are significantly cytotoxic against cancer cells (median inhibitory concentration (IC50): 7.44, 4.61, 5.0 μg/mL respectively) and leishmania parasite (IC50: 1.75, 0.03 and 0.02 μg/mL respectively). Results of biological activities suggest these complexes as attractive therapeutic agents for further in vivo studies except α-amylase inhibition.
- Sarwar, Sidra,Iftikhar, Tuba,Rauf, Muhammad Khawar,Badshah, Amin,Waseem, Durdana,Tahir, Muhammad Nawaz,Khan, Khalid Mohammed,Khan, Gul Majid
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- Bisepoxide cross-linked enzyme aggregates - New immobilized biocatalysts for selective biotransformations
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Glycerol diglycidyl ether (GDE) is a convenient and inexpensive bisepoxide cross-linker as demonstrated by the preparation of cross-linked enzyme aggregates (CLEAs) from two enzyme classes. The GDE CLEAs of lipase from Pseudomonas fluorescens (AK), lipase from Burkholderia cepacia (PS), and lipase B from Candida antarctica (CaL B) as well as of phenylalanine ammonia-lyase (PAL) from Petroselinum crispum demonstrated improved properties as compared with their glutaraldehyde (GA) cross-linked counterparts. Ultrasonication studies indicated that the GDE CLEAs of lipase PS and PAL were mechanically more stable than the GA CLEAs. In the kinetic resolution of rac-1-phenylethanol, the catalytic activity of the GDE-lipase CLEAs (U=69.6, 134.8, and 127.4 U g -1 for AK, CaL B, and PS prepared at 22 °C, respectively) surpassed that of the corresponding GA-lipase CLEAs (U=24.4, 131.0, and 119.2 U g-1 for AK, CaL B, and PS prepared at 22 °C, respectively). The GDE co-CLEAs from PAL and bovine serum albumin (BSA) could be recycled at least three times if used for the stereoselective ammonia addition in 6 M ammonia to (E)-3-(thiophen-2-yl)acrylic acid, whereas the recycling of the conventional GA-PAL CLEAs from this medium failed. The missing linker: Glycerol diglycidyl ether is applied as a cross-linker for cross-linked enzyme aggregates (CLEAs) of various enzymes such as lipases and phenylalanine ammonia lyases. The bisepoxide CLEAs prove to be efficient and robust biocatalysts surpassing the performance of the glutaraldehyde CLEAs.
- Weiser, Diana,Varga, Andrea,Kovacs, Klaudia,Nagy, Flora,Szilagyi, Andras,Vertessy, Beata G.,Paizs, Csaba,Poppe, Laszlo
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- Microwave-Assisted Solvent-Free Synthesis of trans-Cinnamic Acids Using Lithium Chloride as Catalyst
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A simple and efficient procedure has been developed for the synthesis of trans-cinnamic acids 3 by the condensation of aromatic aldehydes 1 with malonic acid 2 using LiCl as catalyst under solvent-free conditions using microwave irradiation. The products are obtained in excellent yields and in a state of high purity.
- Mogilaiah,Reddy, G. Randheer
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- Introducing of potent cytotoxic novel 2-(aroylamino)cinnamamide derivatives against colon cancer mediated by dual apoptotic signal activation and oxidative stress
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Curcumin and trans-cinnamaldehyde are acrolein-based Michael acceptor compounds that are commonly found in domestic condiments, and known to cause cancer cell death via redox mechanisms. Based on the structural features of these compounds we designed and synthesized several 2-cinnamamido-N-substituted-cinnamamide (bis-cinnamamide) compounds. One of the derivatives, (Z)-2-[(E)-cinnamamido]-3-phenyl-N-propylacrylamide 8 showed a moderate antiproliferative potency (HCT-116 cell line inhibition of 32.0 μM), no inhibition of normal cell lines C-166, and proven cellular activities leading to apoptosis. SAR studies led to more than 10-fold increase in activity. Our most promising compound, [(Z)-3-(1H-indol-3-yl)-N-propyl-2-[(E)-3-(thien-2-yl)propenamido)propenamide] 45 killed colon cancer cells at IC50 = 0.89 μM (Caco-2), 2.85 μM (HCT-116) and 1.65 μM (HT-29), while exhibiting much weaker potency on C-166 and BHK normal cell lines (IC50 = 71 μM and 77.6 μM, respectively). Cellular studies towards identifying the compounds mechanism of cytotoxic activities revealed that apoptotic induction occurs in part as a result of oxidative stress. Importantly, the compounds showed inhibition of cancer stem cells that are critical for maintaining the potential for self-renewal and stemness. The results presented here show discovery of covalently acting Michael addition compounds that potently kill cancer cells by a defined mechanism, with prominent selectivity profile over non-cancerous cell lines.
- Abdel-Bakky, Mohamed S.,Abdelghany, Tamer M.,Ahmed, Hany E. A.,Ahmed, Mostafa H.,Boothello, Rio,El-Araby, Moustafa E.,Elhaggar, Radwan S.,Malebari, Azizah M.,Omar, Abdelsattar M.,Patel, Bhaumik B,Safo, Martin K.
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- Iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabled aldehyde C-H methylation
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A practical and general iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabling aldehyde C-H methylation for the synthesis of methyl ketones has been developed. This mild, operationally simple method uses ambient air as the sole oxidant and tolerates sensitive functional groups for the late-stage functionalization of complex natural-product-derived and polyfunctionalized molecules.
- Gong, Pei-Xue,Xu, Fangning,Cheng, Lu,Gong, Xu,Zhang, Jie,Gu, Wei-Jin,Han, Wei
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supporting information
p. 5905 - 5908
(2021/06/18)
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- Enantioselective Rauhut–Currier Reaction with β-Substituted Acrylamides Catalyzed by N-Heterocyclic Carbenes
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β-Substituted acrylamides have low electrophilicity and are yet to be exploited in the enantioselective Rauhut–Currier reaction. By exploiting electron-withdrawing protection of the amide and moderate nucleophilicity N-heterocyclic carbenes, such substrates have been converted to enantioenriched quinolones. The reaction proceeds with complete diastereoselectivity, good yield, and modest enantioselectivity. Derivatizations are reported, as are computational studies, supporting decreased amide bond character with electron-withdrawing protection of the nitrogen.
- Pitchumani, Venkatachalam,Breugst, Martin,Lupton, David W.
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supporting information
p. 9413 - 9418
(2021/12/09)
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- Chlorination Reaction of Aromatic Compounds and Unsaturated Carbon-Carbon Bonds with Chlorine on Demand
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Chlorination with chlorine is straightforward, highly reactive, and versatile, but it has significant limitations. In this Letter, we introduce a protocol that could combine the efficiency of electrochemical transformation and the high reactivity of chlorine. By utilizing Cl3CCN as the chloride source, donating up to all three chloride atom, the reaction could generate and consume the chlorine in situ on demand to achieve the chlorination of aromatic compounds and electrodeficient alkenes.
- Liu, Feng,Wu, Na,Cheng, Xu
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supporting information
p. 3015 - 3020
(2021/05/05)
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- Dual Nickel/Ruthenium Strategy for Photoinduced Decarboxylative Cross-Coupling of α,β-Unsaturated Carboxylic Acids with Cycloketone Oxime Esters
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Herein, a dual nickel/ruthenium strategy is developed for photoinduced decarboxylative cross-coupling between α,β-unsaturated carboxylic acids and cycloketone oxime esters. The reaction mechanism is distinct from previous photoinduced decarboxylation of α,β-unsaturated carboxylic acids. This reaction might proceed through a nickelacyclopropane intermediate. The C(sp2)-C(sp3) bond constructed by the aforementioned reaction provides an efficient approach to obtaining various cyanoalkyl alkenes, which are synthetically valuable organic skeletons in organic and medicinal chemistry, under mild reaction conditions. The protocol tolerates many critical functional groups and provides a route for the modification of complex organic molecules.
- Gao, Ang,Jiang, Run-Chuang,Liu, Chuang-Chuang,Liu, Qi-Le,Lu, Xiao-Yu,Xia, Ze-Jie
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supporting information
p. 8829 - 8842
(2021/06/30)
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- Identification and optimization of piperine analogues as neuroprotective agents for the treatment of Parkinson's disease via the activation of Nrf2/keap1 pathway
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Parkinson's disease (PD) is a slowly progressive and complex neurodegenerative disorder. Up to date, there are no approved drugs that could slow or reverse the neurodegenerative process of PD. Here, we reported the synthesis of series of piperine analogues and the evaluation of their neuroprotective effects against hydrogen peroxide (H2O2) induced damage in the neuron-like PC12 cells. Among these analogues, 3b exhibited the most potent protection effect and its underlying mechanism was further investigated. Further results indicated that the ROS scavenging and cytoprotection effect of 3b might be related to the Nrf2 activation and upregulation of related phase II antioxidant enzymes, such as HO-1 and NQO1. In in vivo study, oral administration (100 mg/kg) of 3b significantly attenuated PD-associated behavioral deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and protected tyrosine hydroxylase-immunopositive dopaminergic neurons. Our results provided evidence that 3b might be a promising candidate for Parkinson's disease treatment.
- Cai, Xiaoying,Chen, Lijuan,Hong, Feng,Kuang, Shuang,Li, Yan,Ma, Xu,Qi, Wenyan,Shi, Mingsong,Wang, Lun,Xu, Ruiling,Xue, Linlin,Ye, Haoyu,Zhang, Ruijia
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- Enantioselective Synthesis of 3,4-Dihydropyran-2-ones via Phase-Transfer-Catalyzed Addition-Cyclization of Acetylacetone to Cinnamic Thioesters
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Herein, we present the first example of synthesis of 3,4-dihydropyran-2-ones from cinnamic thioesters via a stereoselective phase-transfer-catalyzed domino Michael-cyclization reaction with acetylacetone. The reaction proceeded under the catalysis of Cinchona-derived quaternary ammonium phenoxide that, in combination with inorganic bases, provided 3,4-dihydropyran-2-ones in yields of up to 93% and enantioselectivities of up to 88% enantiomeric excess.
- Destro, Dario,Bottinelli, Carlo,Ferrari, Ludovica,Albanese, Domenico C. M.,Bencivenni, Grazia,Gillick-Healy, Malachi W.,Kelly, Brian G.,Adamo, Mauro F. A.
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supporting information
p. 5183 - 5192
(2020/04/10)
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- Organic metal compound and organic light-emitting device
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Organic metal compounds and organic light-emitting devices employing the same are provided. The organic metal compound has a chemical structure of Formula (I) or Formula (II): In particular, one of the following two conditions (1) and (2) is met: (1) R1 is deuterium or C1-6 deuterated alkyl group, when R3 and R4 are independently hydrogen, halogen, C1-6 alkyl group, C1-6 fluoroalkyl or C3-12 heteroaryl group; and (2) R1 is hydrogen, deuterium, C1-6 alkyl group, C1-6 deuterated alkyl group, C3-12 heteroaryl group, or C6-12 aryl group, when at least one of R3 and R4 is C6-12 aryl group or C6-12 fluoroaryl group.
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Paragraph 0041; 0059-0060
(2020/02/10)
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- Photocatalytic decarboxylative alkenylation of α-amino and α-hydroxy acid-derived redox active esters by NaI/PPh3 catalysis
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Herein, we report the photocatalytic decarboxylative alkenylation reactions of N-(acyloxy)phthalimide derived from α-amino and α-hydroxy acids with 1,1-diarylethene, and with cinnamic acid derivatives through double decarboxylation, using sodium iodide and triphenylphosphine as redox catalysts. The reaction proceeds under mild irradiation conditions with visible blue light (440 nm or 456 nm) in an acetone solvent without recourse to transition-metal or organic dye based photoredox catalysts. The reaction proceeds via photoactivation of a transiently self-assembled chromophore from N-(acyloxy)phthalimide and NaI/PPh3. Solvation plays a crucial role in the reactivity.
- Fu, Ming-Chen,Fu, Yao,Shang, Rui,Wang, Ya-Ting,Zhao, Bin
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supporting information
p. 2495 - 2498
(2020/03/06)
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- Piperine derivative as well as preparation method and application thereof
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The invention provides a piperine derivative as well as a preparation method and an application thereof. The piperine derivative is a compound shown as a formula (I), or a salt thereof, or a stereoisomer thereof, or a hydrate thereof. The compound provided by the invention can effectively protect nerve cells and improve the survival rate of the nerve cells, so that the compound provided by the invention can effectively treat neurodegenerative diseases and can be used for preparing medicines for treating the neurodegenerative diseases.
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Paragraph 0269; 0271-0273
(2020/05/08)
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- Radical-Cation Vinylcyclopropane Rearrangements by TiO2Photocatalysis
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Radical cation vinylcyclopropane rearrangements by TiO2 photocatalysis in lithium perchlorate/nitromethane solution are described. The reactions are triggered by oxidative single electron transfer, which is followed by immediate ring-opening of the cyclopropanes to generate distonic radical cations as unique reactive intermediates. This approach can also be applied to vinylcyclobutane, leading to the construction of six-membered rings. A stepwise mechanism via distonic radical cations is proposed based on preliminary mechanistic studies, which is supported by density functional theory calculations.
- Maeta, Naoya,Kamiya, Hidehiro,Okada, Yohei
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supporting information
p. 6551 - 6566
(2020/07/14)
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- Toward a Scalable Synthesis and Process for EMA401, Part II: Development and Scale-Up of a Pyridine- A nd Piperidine-Free Knoevenagel-Doebner Condensation
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During route scouting for EMA401 (1), an angiotensin II type 2 antagonist, we identified the synthesis of key amino acid intermediate 2 via its cinnamic acid derivative 3 as a streamlined option. In general, cinnamic acids can be synthesized from the corresponding aldehydes by a Knoevenagel-Doebner condensation in pyridine with piperidine as an organocatalyst. We aimed to replace both of these reagents and found novel conditions involving toluene as the solvent and morpholine as the organocatalyst. Scale-up of the process allowed the production of 25 kg of cinnamic acid 3 that was of the quality required for process development of the subsequent phenylalanine ammonia lyase-catalyzed step. The modified conditions were found to be widely applicable to alternative aldehydes and thus are of relevance to practitioners of chemical scale-up.
- Hardegger, Leo A.,Humair, Roger,Sidler, Eric
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p. 1756 - 1762
(2020/10/26)
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- Synthesis and characterization of unsaturated diacyl and alkyl-acyl piperazine derivatives
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The aim of this study is to obtain new unsaturated piperazine compounds by the reactions of piperazine (1a) and piperazine derivatives (1b–1d) with acylation reactive groups (2a–2j). Methacryloyl piperazine (1b) was synthesized from the reaction of methacrylic anhydride with piperazine (1a). Acyl chlorides (2b–2d) were prepared from the reaction of thionyl chloride with carboxylic acids (3a–3c) obtained as a result of the reaction with malonic acid and suitable aldehyde (5-methylfuran-2-carbaldehyde for 3a, cinnamaldehyde for 3b, and thiophene-2-carbaldehyde for 3c), respectively, by literature methods. Acyl chlorides 2e and 2f were obtained from the reaction of commercially purchased carboxylic acids 3d and 3e with thionyl chloride. Acyl chlorides (2g–2j) were synthesized from the reaction of thionyl chloride with carboxylic acids (3d–3g) transformed from hydrolyzation of esters (4a–4d) obtained as a result of the reaction of triethyl phosphonoacetate with a suitable ketone (acetophenone for 4a, benzophenone for 4b, 1-(5-methylfuran-2-yl)ethan-1-one for 4c, and 1-(thiophen-2-yl)ethan-1-one for 4d), respectively, by literature methods. Unsaturated piperazine derivatives 5a and 5b were obtained from the reaction of 1b with 2b and 2e, respectively. In addition, from the reaction of 1b and acyl chlorides (2b–2j), unsaturated piperazines (5c–5k) were synthesized in medium to good yields (63%–84%). Also, 5l–5g and 5r–5w were obtained from the reaction of allyl piperazine (2c) and cinnamyl piperazine (2d) with acyl chlorides (2a–2f).
- Sari, Sait,ünalan, Seda,Yilmaz, Mehmet
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p. 1656 - 1671
(2020/01/03)
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- Synthesis and biological evaluation of 2,2-dimethylbenzopyran derivatives as potent neuroprotection agents
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The development of novel neuroprotection agents is of great significance for the treatment of ischemic stroke. In this study, a series of compounds comprising 2,2-dimethylbenzopyran groups and cinnamic acid groups have been synthesized. Preferential combination principles and bioisostere that improved the neuroprotective effect of the compounds were identified for this series via biological activity assay in vitro. Meanwhile, a functional reversal group of the acrylamide amide resulted in the most active compounds. Among them, BN-07 significantly improved the morphology of neurons and obviously increased cell survival rate of primary neurons induced by oxygen glucose deprivation (OGD), superior to clinically used anti-ischemic stroke drug edaravone (Eda). Overall, our findings may provide an alternative strategy for the design of novel anti-ischemic stroke agents with more potency than Eda.
- Du, Fangyu,Zhou, Qifan,Fu, Xiaoxiao,Shi, Yajie,Chen, Yuanguang,Fang, Wuhong,Yang, Jingyu,Chen, Guoliang
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p. 2498 - 2508
(2019/02/01)
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- Synthesis and Hypoglycemic Activity of Aryl(Hetaryl)Propenoic Cyanopyrrolidine Amides
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Abstract: A series of amides based on (2S)-cyanopyrrolidine and α, β-unsaturated aryl- and hetarylcarboxylic acids have been synthesized. The dependence of the hypoglycemic activity of compounds on the structure of the aromatic fragment has been studied in the oral glucose tolerance test in mice. Amides based on (E)-3-phenylprop-2-enoic and (E)-3-(4-methoxyphenyl)prop-2-enoic acids and (2S)-cyanopyrrolidine have been shown to significantly reduce blood glucose levels in mice. The observed hypoglycemic effect at a dose of 10 mg/kg is comparable to the effect of hypoglycemic drug vildagliptin.
- Kuranov,Blokhin,Borisov,Khvostov,Luzina,Salakhutdinov
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p. 374 - 380
(2019/10/28)
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- Utility of 3-(thiophen-2-yl)prop-2-enoyl isothiocyanate in heterocyclic synthesis
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Convenient syntheses of quinazoline, benzothiazole, thiadiazole, imidazole, and thiourea derivatives starting from 3-(thiophen-2-yl)prop-2-enoyl isothiocyanate are described. The structures of the synthesized compounds are confirmed from their microanalytical and spectral data. Some of the products are examined for their antibacterial activity against Gram-positive and Gram-negative bacteria and fungi.
- El-Sayed, Amira A,Atta-Allah, Saad R,Hemdan, Magdy M
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p. 307 - 312
(2019/07/19)
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- Oxime-derived palladacycle Immobilized in an Ionic Liquid Brush as an Efficient and Reusable Catalyst for Mozoroki-Heck Reaction in Neat Water
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An efficient and reusable heterogeneous catalyst with oxime-derived palladacycle immobilized in an ionic liquid brush has been synthesized and an environmentally-friendly procedure have been developed for coupling aryl iodides and bromides with acrylic acid. These reactions were conducted in neat water under aerobic conditions with water-insoluble or even solid aryl halides and they proceeded smoothly and cleanly without any organic co-solvent or other additives. The ionic liquid brush could be easily recovered and reused at least five times without significant loss of activity. The protocol has the advantages of excellent yields, environmental friendliness, and catalyst recyclability.
- Wang, Rong,Li, Shan,Li, Jing,Wei, Junfa
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- Method of coupling, and the coupling method using the aromatic group-substituted heterocyclic compound
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Provided is an easy method (coupling method) capable of easily synthesizing a compound group in which aromatic molecules and aromatic molecules are coupled, a compound group in which aromatic molecules and alkene molecules are coupled, and the like without producing halogen waste and without the need to use scarce and expensive palladium. A compound (A) shown by general formula (A): Ar-H and a compound (B1) shown by general formula (B1): RaOCO-Ar', a compound (B2) shown by general formula (B2): RbCH=C(Ar")2, or a compound (B3) shown by general formula (B3): RcOCOCH=C(Ar")2 are reacted in the presence of a nickel compound.
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Paragraph 0226-0227; 0229
(2020/09/17)
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- 2,2-dimethylbenzopyran derivative and preparation method and use thereof
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The invention belongs to the technical field of medicines, and discloses a 2,2-dimethylbenzopyran derivative and a preparation method and use of the 2,2-dimethylbenzopyran derivative. The derivative and pharmaceutically acceptable salt of the derivative have the structural formulae shown in the description, wherein Ar, Ar, X, Y and R1 are as described in the claims and the description. The preparation methods of the derivative and the pharmaceutically acceptable salt of the derivative comprise the following steps: the formula (I) is obtained by mainly taking acetaminophen as a raw material, and subjected to the reactions of Williamson ether formation, cyclization, hydrolysis, amide formation and the like; the formula II is obtained by mainly taking p-hydroxybenzaldehyde as a raw material, and subjected to the reactions of the Williamson ether formation, cyclization, Knoevenagel condensation, amide formation and the like. The derivative and the pharmaceutically acceptable salt ofthe derivative disclosed by the invention can be used for preparing neuroprotective agents and have better neuroprotective effects on ischemic stroke.
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Page/Page column 13; 14
(2019/01/16)
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- Piperlongumine derived cyclic sulfonamides (sultams): Synthesis and in?vitro exploration for therapeutic potential against HeLa cancer cell lines
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A novel modification of piperlongumine is designed, bearing a cyclic sulphonamide (sultam) and its synthesis is described. For the first time herein we report the synthesis and biological evaluation of the natural product derived cyclic sulfonamides using Grubbs second generation catalyst (Grubbs II) via ring closing metathesis approach. Synthesis of a series of piperlongumine derived sultams is done in a moderate to good yield using Wittig reaction, Ring-Closing Metathesis (RCM) and, amide synthesis by using mixed anhydride, approach. All synthesized compounds were evaluated for anticancer activity and some demonstrated dose dependent reduction in HeLa cell growth. Of these 7, 10 and 14 significantly reduced the cell growth. Consequently their calculated GI50values were found to be 0.1 or 0.1?μM.
- Lad, Nitin P.,Kulkarni, Sarang,Sharma, Rajiv,Mascarenhas, Malcolm,Kulkarni, Mahesh R.,Pandit, Shivaji S.
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p. 870 - 878
(2016/12/18)
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- One-pot synthesis of fused 2-pyridones from heteroarylacrylic acid via curtius rearrangement & microwave-assisted thermal electrocyclization
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We investigated the one-pot synthesis of several fused 2-pyridone ring systems based on a Curtius rearrangement, followed by a microwave-assisted thermal electrocyclization of a 2-aza-6?-electron system including isocyanate. We synthesized seven heterocyclic compounds containing a fused 2-pyridone ring. In these results, the one-pot synthesis of fused 2-pyridone ring system 5 from (E)-acrylic acids 1 under microwave irradiation conditions was more effective than the conventional reaction conditions in terms of the yield and the reaction time.
- Nishiyama, Takashi,Hatae, Noriyuki,Hayashi, Kaori,Obata, Manami,Taninaka, Kimiko,Yamane, Masahiro,Oda, Shota,Abe, Takumi,Ishikura, Minoru,Hibino, Satoshi,Choshi, Tominari
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p. 251 - 267
(2017/07/28)
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- Carboxylation of styrenes with CBr4 and DMSO via cooperative photoredox and cobalt catalysis
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Cooperative photoredox and cobalt catalyzed carboxylation of styrenes with CBr4 to afford the corresponding α,β-unsaturated carboxylic acids has been realized through radical addition and Kornblum (DMSO) oxidation. DMSO serves as the oxidant, oxygen source and solvent under these photocatalytic conditions.
- Song, Cai-Xia,Chen, Ping,Tang, Yu
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p. 11233 - 11243
(2017/02/26)
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- Enantioselective Synthesis of N?H-Free 1,5-Benzothiazepines
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An enantioselective sulfa-Michael-cyclization reaction was developed for the synthesis of 1,5-benzothiazepines with versatile pharmacological activities. The reaction between 2-aminothiophenol and α,β-unsaturated pyrazoleamides gave direct access to N?H-free 1,5-benzothiazepines in the presence of a chiral N,N′-dioxide/Yb(OTf)3complex. Excellent enantioselectivities (up to 96 % ee) and high yields (up to 99 %) were obtained for a broad range of substrates under mild reaction conditions. This method provided a facile approach to the antidepressant drug (R)-(?)-Thiazesim.
- Wang, Guojin,Tang, Yu,Zhang, Yu,Liu, Xiaohua,Lin, Lili,Feng, Xiaoming
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supporting information
p. 554 - 557
(2017/01/18)
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- Photoinduced, Copper-Promoted Regio- and Stereoselective Decarboxylative Alkylation of α,β-Unsaturated Acids with Alkyl Iodides
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The first example of UV light-induced, copper-catalyzed regio- and stereoselective decarboxylative coupling of α,β-unsaturated acids with alkyl iodides was reported. Under standard conditions, the 1°, 2°, and 3° alkyl iodides proceeded smoothly with the E-selective alkenes obtained in uniformly good yields and high stereoselectivities.
- Wang, Chao,Lei, Yingjie,Guo, Mengzhun,Shang, Qinyu,Liu, Hong,Xu, Zhaoqing,Wang, Rui
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supporting information
p. 6412 - 6415
(2017/12/08)
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- Iodine-Catalyzed Facile Approach to Sulfones Employing TosMIC as a Sulfonylating Agent
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A novel iodine-catalyzed functionalization of a variety of olefins and alkynes and direct decarboxylative functionalization of cinnamic and propiolic acids with TosMIC to provide access to various vinyl, allyl, and β-iodo vinylsulfones is described. This simple, efficient, and environmentally benign approach employing inexpensive molecular iodine as a catalyst demonstrates a versatile protocol for the synthesis of highly valuable sulfones, rendering it attractive to both synthetic and medicinal chemistry.
- Kadari, Lingaswamy,Palakodety, Radha Krishna,Yallapragada, Lakshmi Prapurna
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supporting information
p. 2580 - 2583
(2017/05/24)
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- Synthesis and bioactivities of novel piperazine-containing 1,5-Diphenyl-2-penten-1-one analogues from natural product lead
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A series of novel 1,5-Diphenyl-2-penten-1-one analogues (7a–h, 8a–h) with piperazine moiety have been designed and synthesized on the basis of natural product 1,5-Diphenyl-2-penten-1-one (I). All the synthesized compounds were evaluated in vitro for anti-plant pathogenic fungi activities and insecticidal activities. The results indicated that most of these analogues exhibited moderate antifungal activities and moderate to good insecticidal activities. Amongst them, the most potent 7c, 7e and 7h keep a mortality of 100% against larva of mosquito at the concentration of 1?mg/L. Initial structure–activity relationship (SAR) analysis showed that, a methyl group can influence the biological activities of these compounds significantly, the compounds with N′-unsubstituted piperazine showed much better antifungal activities and larvicidal activity against mosquito than the compounds with N′-methylated piperazine. In addition, the larvicidal activity against mosquito had sharply decline when the substituent on benzene ring was changed from 4-position to 2 or 3-position.
- Xu, Gaofei,Yang, Xinling,Jiang, Biaobiao,Lei, Peng,Liu, Xili,Wang, Qingmin,Zhang, Xuebo,Ling, Yun
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p. 1849 - 1853
(2016/07/27)
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- Synthesis and biological evaluation of (E)-cinnamic acid, (E)-2-styrylthiazole and (E)-2-[2-(naphthalen-1-yl)vinyl]thiazole derivatives
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Cinnamyl- and thiazole-based compounds have been shown to exhibit diverse medicinal properties and a series of twelve (E)-2-styrylthiazole and (E)-2-[(naphthalen-1-yl)vinyl]thiazole derivatives, which are conjugates of both systems and which satisfy the "Lipinski rule of 5", have been synthesised and subjected to in vitro biological screening. While insignificant inhibition (60-98% viability at 10 μM) of HeLa (cervical cancer) cells was noted, all five of the (E)-2-[naphthalen-1- yl)vinyl]thiazole derivatives proved remarkably active against SH-SY5Y (neuroblastoma) cells with IC50 values ranging from 2.09 to 8.64 μM. Two of the seven (E)-2-styrylthiazoles were found to be moderately active (with IC50 values of 10.8 and 11.7 mM), whereas the remaining five analogues exhibit significant proliferation of SH-SY5Y cells (with IC50 values of 180-1000 mM). The results warrant further studies on the effects of styrylthiazoles on the differentiation and extension of SH-SY5Y cells in order to assess their activity in neurological degenerative diseases.
- Olawode, Emmanuel O.,Tandlich, Roman,Prinsloo, Earl,Isaacs, Michelle,Hoppe, Heinrich,Seldon, Ronnett,Warner, Digby F.,Steenkamp, Vanessa,Kaye, Perry T.
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p. 284 - 296
(2018/03/09)
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- Synthesis and biological evaluation of (E)-cinnamic acid, (E)-2-styrylthiazole and (E)-2-[2-(naphthalen-1-yl)vinyl]thiazole derivatives
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Cinnamyl- and thiazole-based compounds have been shown to exhibit diverse medicinal properties and a series of twelve (E)-2-styrylthiazole and (E)-2-[(naphthalen-1-yl)vinyl]thiazole derivatives, which are conjugates of both systems and which satisfy the “Lipinski rule of 5”, have been synthesised and subjected to in vitro biological screening. While insignificant inhibition (60-98% viability at 10 μM) of HeLa (cervical cancer) cells was noted, all five of the (E)-2-[naphthalen-1-yl)vinyl]thiazole derivatives proved remarkably active against SH-SY5Y (neuroblastoma) cells with IC50 values ranging from 2.09 to 8.64 μM. Two of the seven (E)-2-styrylthiazoles were found to be moderately active (with IC50 values of 10.8 and 11.7 mM), whereas the remaining five analogues exhibit significant proliferation of SH-SY5Y cells (with IC50 values of 180-1000 mM). The results warrant further studies on the effects of styrylthiazoles on the differentiation and extension of SH-SY5Y cells in order to assess their activity in neurological degenerative diseases.
- Olawode, Emmanuel O.,Tandlich, Roman,Prinsloo, Earl,Isaacs, Michelle,Hoppe, Heinrich,Seldon, Ronnett,Warner, Digby F.,Steenkamp, Vanessa,Kaye, Perry T.
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p. 284 - 296
(2018/05/09)
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- Synthesis and fungicidal activity study of novel daphneolone analogs with 2,6-dimethylmorpholine
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A series of novel daphneolone analogs was designed and synthesized on the basis of natural product 1,5-diphenyl-2-penten-1-one (I) from Stellera chamaejasme L. as lead compound, whereby 2,6-dimethylmorpholine moiety was introduced to replace 1-phenyl group. Their structures were confirmed by IR, 1H NMR, and HRMS (ESI) or elemental analysis, 13C NMR for some representative compounds. The two isomers of target compounds were separated and identified by NOESY technique and chemical method. All of the synthesized compounds have been evaluated for anti-plant pathogenic fungi activities. The results showed that some compounds exhibited moderate to good antifungal activities against tested fungi at the concentration of 50 mg/L. Among them, compound 7d, with a 4-bromine-substituted phenyl group and cis-2,6-dimethylmorpholine moiety, displayed best activity with an EC50 of 23.87 μmol/L against Valsa Mali, superior to lead compound I. In addition, preliminary structure-activity relationship analysis indicated that, between two isomers of target compounds, the antifungal activities of the isomer with cis-2,6-dimethylmorpholine were better than the trans-isomer.
- Xu, Gao-Fei,Yang, Xin-Ling,Lei, Peng,Liu, Xi-Li,Zhang, Xue-Bo,Ling, Yun
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supporting information
p. 555 - 558
(2016/04/26)
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- 3-aryl acrylic acid and its derivatives viral anti-plant
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The invention relates to an application of 3-aryl acrylic acid represented by a general formula (I) and a derivative thereof in pesticides, wherein the 3-aryl acrylic acid and the derivative thereof can be adopted as novel anti-plant virus agents, can be provided for well inhibiting tobacco mosaic virus, pepper virus, tomato virus, sweet potato virus, potato virus, melon virus, maize dwarf mosaic virus and the like, and can be provided for effectively preventing and controlling virus diseases of a plurality of crops such as tobacco, pepper, tomato, melon vegetables, grains, vegetables, beans and the like, especially tobacco mosaic diseases. (Wherein Ar and R are defined in an instruction).
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-
Paragraph 0022; 0023
(2016/11/21)
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- Influence of the aromatic moiety in α- And β-arylalanines on their biotransformation with phenylalanine 2,3-aminomutase from: Pantoea agglomerans
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In this study enantiomer selective isomerization of various racemic α- and β-arylalanines catalysed by phenylalanine 2,3-aminomutase from Pantoea agglomerans (PaPAM) was investigated. Both α- and β-arylalanines were accepted as substrates when the aryl moiety was relatively small, like phenyl, 2-, 3-, 4-fluorophenyl or thiophen-2-yl. While 2-substituted α-phenylalanines bearing bulky electron withdrawing substituents did not react, the corresponding substituted β-aryl analogues were converted rapidly. Conversion of 3- and 4-substituted α-arylalanines happened smoothly, while conversion of the corresponding β-arylalanines was poor or non-existent. In the range of pH 7-9 there was no significant influence on the conversion of racemic α- or β-(thiophen-2-yl)alanines, whereas increasing the concentration of ammonia (ammonium carbonate from 50 to 1000 mM) inhibited the isomerization progressively and decreased the amount of the by-product (i.e. (E)-3-(thiophen-2-yl)acrylic acid was detected). In all cases, the high ee values of the products indicated excellent enantiomer selectivity and stereospecificity of the isomerization except for (S)-2-nitro-α-phenylalanine (ee 92%) from the β-isomer. Substituent effects were rationalized by computational modelling revealing that one of the main factors controlling biocatalytic activity was the energy difference between the covalent regioisomeric enzyme-substrate complexes.
- Varga, Andrea,Bánóczi, Gergely,Nagy, Botond,Bencze, László Csaba,To?a, Monica Ioana,Gellért, ákos,Irimie, Florin Dan,Rétey, János,Poppe, László,Paizs, Csaba
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p. 56412 - 56420
(2016/07/06)
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- Cu/Fe-Cocatalyzed Formation of β-Ketophosphonates by a Domino Knoevenagel-Decarboxylation-Oxyphosphorylation Sequence from Aromatic Aldehydes and H-Phosphonates
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A domino Knoevenagel-decarboxylation-alkene difunctionalization sequence has been developed for the conversion of benzaldehydes into β-ketophosphonates, catalyzed by a cooperative Cu/Fe system, whereby CP and CO bonds are formed simultaneously in a one-pot reaction. The reaction proceeds in good yields and with a broad substrate scope and environmentally benign conditions.
- Zhou, Mingxin,Zhou, Yao,Song, Qiuling
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supporting information
p. 10654 - 10658
(2015/07/20)
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- Synthesis and antibacterial activity of 4'3-O-(trans-β-arylacrylamido)carbamoyl azithromycin analogs
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Novel 4'3-O-(trans-β-arylacrylamido)carbamoyl azithromycin analogs were designed, synthesized and evaluated for their antibacterial activity against nine significant pathogens using broth microdilution method. A majority of these derivatives maintained the activity of azithromycin against susceptible Streptococcus pyogenes and all the compounds demonstrated remarkably improved activity compared with the references against all the three phenotypes of resistant Streptococcus pneumoniae. In particular, compound 24 exhibited the most potent activity against susceptible Staphylococcus aureus (MIC = 0.5 μg/mL), S. pneumoniae (MIC = 0.06 μg/mL) and S. pyogenes (MIC = 0.25 μg/mL). The most active compound 7 (MIC = 0.015 μg/mL) against resistant S. pneumoniae expressing the mefA gene, exhibited 512 and 256-fold more potent activity than erythromycin and azithromycin, respectively. Compounds 28 (MIC = 0.5 μg/mL), 29 (MIC = 0.25 μg/mL) and 30 (MIC = 0.5 μg/mL) demonstrated potent activity against resistant S. pneumoniae expressing the ermB gene, which were 256, 512 and 256-fold better than the references, respectively.
- Yan, Mi,Ma, Xiaodong,Dong, Ruiqian,Li, Xin,Zhao, Can,Guo, Zhenzhen,Shen, Yan,Liu, Fang,Ma, Ruixin,Ma, Shutao
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p. 506 - 515
(2015/10/06)
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- Synthesis of 2-(hetero)aryl-5-(trimethylsilylethynyl)oxazoles from (hetero)arylacrylic acids
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A three-step method for the synthesis of 2-(hetero)aryl-5-(trimethylsilylethynyl)oxazoles is described. Easily accessible bis(trimethylsilyl)acetylene and acrylic acid derivatives are used as starting materials for the preparation of mono- and disubstituted 5-(trimethylsilyl)pent-1-en-4-yn-3-ones. Oxidative phthalimidoaziridination of these enynones provides the key 2-acyl-1-phthalimidoaziridines that are further utilized in the thermal expansion of the three-membered ring to furnish the target functionalizable oxazoles.
- Pankova, Alena S.,Stukalov, Alexander Yu.,Kuznetsov, Mikhail A.
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supporting information
p. 1826 - 1829
(2015/04/27)
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- Chiral Cyclopentadienyl Iridium(III) Complexes Promote Enantioselective Cycloisomerizations Giving Fused Cyclopropanes
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The cyclopentadienyl (Cp) group is a very important ligand for many transition-metal complexes which have been applied in catalysis. The availability of chiral cyclopentadienyl ligands (Cpx) lags behind other ligand classes, thus hampering the investigation of enantioselective processes. We report a library of chiral CpxIrIII complexes equipped with an atropchiral Cp scaffold. A robust complexation procedure reliably provides CpxIrIII complexes with tunable counterions. In a proof-of-concept application, the iodide-bearing members are shown to be highly selective for enyne cycloisomerization reactions. The dehydropiperidine-fused cyclopropane products are formed in good yields and enantioselectivities.
- Dieckmann, Michael,Jang, Yun-Suk,Cramer, Nicolai
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supporting information
p. 12149 - 12152
(2015/10/12)
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- Copper catalyzed oxygen assisted C(CNOH)-C(alkyl) bond cleavage: A facile conversion of aryl/aralkyl/vinyl ketones to aromatic acids
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A novel copper-catalyzed aerobic oxidative C(NOH)-C(alkyl) bond cleavage reaction of aryl/aralkyl/vinyl ketones for the synthesis of aromatic/acrylic acids is described. A series of ketones having aryl/aralkyl/vinyl at the one end and methyl to any higher alkyl at the other end can be selectively cleaved and converted into the corresponding acids via oxime intermediates.
- Sathyanarayana, Pochampalli,Ravi, Owk,Muktapuram, Prathap Reddy,Bathula, Surendar Reddy
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supporting information
p. 9681 - 9685
(2015/09/28)
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- Butyrolactone synthesis via polar radical crossover cycloaddition reactions: Diastereoselective syntheses of methylenolactocin and protolichesterinic acid
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A direct catalytic synthesis of γ-butyrolactones from simple alkene and unsaturated acid starting materials is reported. The catalytic system consists of the Fukuzumi acridinium photooxidant and substoichiometric quantities of a redox-active cocatalyst. Oxidizable alkenes such as styrenes and trisubstituted aliphatic alkenes are cyclized with unsaturated acids via polar radical crossover cycloaddition (PRCC) reactions. This method has been applied to the diastereoselective total synthesis of methylenolactocin and protolichesterinic acid.
- Zeller, Mary A.,Riener, Michelle,Nicewicz, David A.
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supporting information
p. 4810 - 4813
(2015/04/27)
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- An efficient synthesis of conjugated 5-aryl-1,3,4-oxadiazoles from 3-heteroarylacrylohydrazides and acid chlorides
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New derivatives of 5-aryl-2-[2-(2-furyl)ethenyl]-1,3,4-oxadiazoles and 5-aryl-2-[2-(2-thienyl)ethenyl]-1,3,4-oxadiazoles are synthesized in a stepwise procedure through intermediate acyclic N′-arylcarbonyl-N-[2-(2-heteroaryl) acryloyl]hydrazines, starting from 3-(2-heteroaryl)acrylic acid hydrazides and acid chlorides. A facile one-pot methodology leading to the final 1,3,4-oxadiazoles is also described.
- Kudelko, Agnieszka,Wróblowska, Monika
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supporting information
p. 3252 - 3254
(2014/06/09)
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- Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents
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A series of ninety-seven diarylpentanoid derivatives were synthesized and evaluated for their anti-inflammatory activity through NO suppression assay using interferone gamma (IFN-γ)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Twelve compounds (9, 25, 28, 43, 63, 64, 81, 83, 84, 86, 88 and 97) exhibited greater or similar NO inhibitory activity in comparison with curcumin (14.7 ± 0.2 μM), notably compounds 88 and 97, which demonstrated the most significant NO suppression activity with IC50 values of 4.9 ± 0.3 μM and 9.6 ± 0.5 μM, respectively. A structure-activity relationship (SAR) study revealed that the presence of a hydroxyl group in both aromatic rings is critical for bioactivity of these molecules. With the exception of the polyphenolic derivatives, low electron density in ring-A and high electron density in ring-B are important for enhancing NO inhibition. Meanwhile, pharmacophore mapping showed that hydroxyl substituents at both meta- and para-positions of ring-B could be the marker for highly active diarylpentanoid derivatives.
- Leong, Sze Wei,Mohd Faudzi, Siti Munirah,Abas, Faridah,Mohd Aluwi, Mohd Fadhlizil Fasihi,Rullah, Kamal,Wai, Lam Kok,Abdul Bahari, Mohd Nazri,Ahmad, Syahida,Tham, Chau Ling,Shaari, Khozirah,Lajis, Nordin H.
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p. 16058 - 16081
(2015/01/08)
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- Multitarget molecular hybrids of cinnamic acids
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In an attempt to synthesize potential new multitarget agents, 11 novel hybrids incorporating cinnamic acids and paracetamol, 4-/7-hydroxycoumarin, benzocaine, p-aminophenol and m-aminophenol were synthesized. Three hybrids - 2e, 2a, 2g - and 3b were found to be multifunctional agents. The hybrid 2e derived from the phenoxyphenyl cinnamic acid and m-acetamidophenol showed the highest lipoxygenase (LOX) inhibition and analgesic activity (IC50 = 0.34 μM and 98.1%, whereas the hybrid 3b of bromobenzyloxycinnamic acid and hymechromone exhibited simultaneously good LOX inhibitory activity (IC50 = 50 μM) and the highest anti-proteolytic activity (IC50= 5 μM). The hybrid 2a of phenyloxyphenyl acid with paracetamol showed a high analgesic activity (91%) and appears to be a promising agent for treating peripheral nerve injuries. Hybrid 2g which has an ester and an amide bond presents an interesting combination of anti-LOX and anti-proteolytic activity. The esters were found very potent and especially those derived from paracetamol and m-acetamidophenol. The amides follow. Based on 2D-structure-activity relationships it was observed that both steric and electronic parameters play major roles in the activity of these compounds. Molecular docking studies point to the fact that allosteric interactions might govern the LOX-inhibitor binding.
- Peperidou, Aikaterini,Hadjipavlou-Litina, Dimitra,Kapoukranidou, Dorothea,Kontogiorgis, Christos
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p. 20197 - 20226
(2015/03/13)
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- Titanium-catalyzed intermolecular hydroaminoalkylation of conjugated dienes
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Ti me kangaroo down: Conjugated dienes undergo intermolecular hydroaminoalkylation in the presence of Ti catalyst [Ind2TiMe 2] (Ind=η5-indenyl). This new reaction offers a highly atom-efficient approach to homoallylic amines from 1,3-butadienes. Copyright
- Preuss, Till,Saak, Wolfgang,Doye, Sven
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supporting information
p. 3833 - 3837
(2013/04/24)
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- ACRYLAMIDE COMPOUNDS AND USE THEREOF FOR INHIBITING APOPTOSIS
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The present invention relates to a compound of Formula I, or an isomer, pharmaceutically acceptable salt and solvate thereof; the present invention also relates to a composition comprising a compound of Formula I, or an isomer, pharmaceutically acceptable salt and solvate thereof, and a pharmaceutically acceptable carrier, excipient or diluents. The present invention also relates to use of a compound of Formula I, or an isomer, pharmaceutically acceptable salt and solvate thereof for combating apoptosis, preventing or treating a disease or disorder associated with apoptosis; especially use for protecting cardiomyocyte, preventing or treating a disease or disorder associated with cardiomyocyte apoptosis.
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-
Paragraph 0037; 0038
(2013/04/10)
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- BENZOTHIOPHENE SULFONAMIDES AND OTHER COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN
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The present invention relates to benzothiophene sulfonamides and other compounds that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.
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-
Page/Page column 355
(2013/12/03)
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- Thiophenium-ylides: Synthesis and reactivity
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The reaction of propanedioic acid, 2-diazo-1,3-bis(1,1-dimethylethyl) ester (di-tert-butyl diazomalonate) with a series of cyclopenta[b]thiophenes in the presence of catalytic rhodium acetate was studied. The resulting SC ylides underwent a rearrangement to form a heterocycle with different topology; thialene, in very low yields. Experimental and spectral data for all compounds are provided.
- MacHara, Ales,Svoboda, Jiri
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p. 59 - 65,7
(2020/08/24)
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- Design, synthesis and biological evaluation of benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of glycogen synthase kinase-3β (GSK-3β)
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Glycogen synthase kinase-3β (GSK-3β) plays a key role in type II diabetes and Alzheimer's diseases, to which non-ATP competitive inhibitors represent an effectively therapeutical approach due to their good specificity. Herein, a series of small molecules benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of GSK-3β have been designed and synthesized. The in vitro evaluation performed by luminescent assay showed most BTZ derivatives have inhibitory effects in micromolar scale. Among them compounds 6l, 6t and 6v have the IC50 values of 25.0 μM, 27.8 μM and 23.0 μM, respectively. Moreover 6v is devoid of any inhibitory activity in the assays to other thirteen protein kinases. Besides, SAR is analyzed and a hypothetical enzymatic binding mode is proposed by molecular docking study, which would be useful for new candidates design.
- Zhang, Peng,Hu, Hai-Rong,Bian, Shi-Hui,Huang, Zhao-Hui,Chu, Yong,Ye, De-Yong
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- Efficient synthesis of 1,3,4-oxadiazoles conjugated to thiophene or furan rings via an ethenyl linker
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A novel and efficient synthesis of 5-substituted 2-[2-(2-furyl)ethenyl]-1, 3,4-oxadiazoles and 2-[2-(2-thienyl)ethenyl]-1,3,4-oxadiazoles by cyclocondensation of the appropriate 3-(2-furyl)- and 3-(2-thienyl) acrylohydrazides with triethyl orthoesters in the presence of glacial acetic acid is reported. The formation of symmetrically substituted 2,5-bis[2-(2-furyl)ethenyl]-1,3,4-oxadiazole and 2,5-bis[2-(2-thienyl)ethenyl]- 1,3,4-oxadiazole from the corresponding N,N′-diacylhydrazines under the influence of phosphorus oxychloride is also described. Georg Thieme Verlag Stuttgart. New York.
- Kudelko, Agnieszka,Jasiak, Karolina
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p. 1950 - 1954
(2013/07/26)
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