- Microwave-assisted rapid synthesis of spirooxindole-pyrrolizidine analogues and their activity as anti-amyloidogenic agents
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A library of Sox-pyrrolizidines was rapidly prepared by microwave-assisted, one-pot, three-component, 1,3-dipolar cycloaddition of azomethine ylides from l-proline and isatin, with various β-nitrostyrenes. Nitro-Sox compounds, 4b, 4d and 4e inhibit HEWL amyloid fibril formation by ThT studies with percentages of fluorescence intensity of 55.4, 42.9 and 40.3%, respectively. Further studies with MTT assay, Raman spectroscopy, TEM and molecular docking supported these promising candidates for activity against amyloid misfolding, a phenomenon leading to Alzheimer's disease pathology.
- de Silva, Nilamuni H.,Pyreddy, Suneela,Blanch, Ewan W.,Hügel, Helmut M.,Maniam, Subashani
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supporting information
(2021/07/07)
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- A green metal-free "one-pot" microwave assisted synthesis of 1,4-dihydrochromene triazoles
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The synthesis of several 4-aryl-1,4-dihydrochromene-triazoles was achieved via a metal-free "one-pot"procedure using PEG400 as the sole solvent in an eco-friendly process. Using microwave irradiation, the triazole derivatives were obtained in good yields and short reaction times starting from readily accessible building blocks.
- Alves, Tania M. F.,Jardim, Guilherme A. M.,Ferreira, Marco A. B.
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p. 10336 - 10339
(2021/03/26)
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- Structure–activity relationship and biological evaluation of berberine derivatives as PCSK9 down-regulating agents
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein and its deficiency markedly enhanced the survival rate of patient with cardiovascular diseases (CVDs). Forty berberine (BBR) derivatives were synthesized and evaluated for their activities on down-regulating the transcription of PCSK9 in HepG2 cells, taking BBR as the lead. Structure–activity relationship (SAR) analysis revealed that 2,3-dimethoxy moiety might be beneficial for activity. Among them, 9k displayed the most potent activity with IC50 value of 9.5 ± 0.5 μM, better than that of BBR. Also, it significantly decreased PCSK9 protein level at cellular level, as well as in the liver and serum of mice in vivo. Furthermore, 9k markedly increased LDLR expression and LDL-C clearance via down-regulating PCSK9 protein. The mechanism of action of 9k is targeting HNF1α and/or Sp1 cluster modulation upstream of PCSK9, a different one from BBR. Therefore, 9k might have the potential to be a novel PCSK9 transcriptional inhibitor for the treatment of atherosclerosis, worthy for further investigation.
- Fan, Tian-Yun,Yang, Yu-Xin,Zeng, Qing-Xuan,Wang, Xue-Lei,Wei, Wei,Guo, Xi-Xi,Zhao, Li-Ping,Song, Dan-Qing,Wang, Yan-Xiang,Wang, Li,Hong, Bin
-
-
- Synthesis and Functional Characterization of 2-(2,5-Dimethoxyphenyl)-N-(2-fluorobenzyl)ethanamine (25H-NBF) Positional Isomers
-
Serotonergic psychedelics, substances exerting their pharmacological action through activation of the serotonin 2A receptor (5-HT2AR), have continuously comprised a substantial fraction of the over 1000 reported New Psychoactive Substances (NPS) so far. Within this category, N-benzyl derived phenethylamines, such as NBOMes and NBFs, have shown to be of particular relevance. As these substances remain incompletely characterized, this study aimed at synthesizing positional isomers of 25H-NBF, with two methoxy groups placed on different positions of the phenyl group of the phenethylamine moiety. These isomers were then functionally characterized in an in vitro bioassay monitoring the recruitment of β-Arrestin 2 to the 5-HT2AR through luminescent readout via the NanoBiT technology. The obtained results provide insight into the optimal substitution pattern of the phenyl group of the phenethylamine moiety of N-benzyl derived substances, a feature so far mostly explored in the phenethylamines underived at the N-position. In the employed bioassay, the most potent substances were 24H-NBF (EC50 value of 158 nM), 26H-NBF (397 nM), and 25H-NBF (448 nM), with 23H-NBF, 35H-NBF, and 34H-NBF yielding μM EC50 values. A similar ranking was obtained for the compounds' efficacy: Taking as a reference LSD (lysergic acid diethylamide), 24H-, 26H-, and 25H-NBF had an efficacy of 106-107%, followed by 23H-NBF (96.1%), 34H-NBF (75.2%), and 35H-NBF (58.9%). The stronger activity of 24H-, 25H-, and 26H-NBF emphasizes the important role of the methoxy group at position 2 of the phenethylamine moiety for the in vitro functionality of NBF substances.
- Pottie, Eline,Kupriyanova, Olga V.,Shevyrin, Vadim A.,Stove, Christophe P.
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p. 1667 - 1673
(2021/05/31)
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- A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells
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Small-molecule inhibitors of p97 are useful tools to study p97 function. Human p97 is an important AAA ATPase due to its diverse cellular functions and implication in mediating the turnover of proteins involved in tumorigenesis and virus infections. Multi
- Zhang, Gang,Li, Shan,Wang, Feng,Jones, Amanda C.,Goldberg, Alexander F.G.,Lin, Benjamin,Virgil, Scott,Stoltz, Brian M.,Deshaies, Raymond J.,Chou, Tsui-Fen
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-
- Dipolar HCP materials as alternatives to DMF solvent for azide-based synthesis
-
Hypercrosslinked polymers HCP-DMF and HCP-DMF-SO3H containing abundant and flexible DMF moieties were designed and synthesized. Benefitting from the solvation microenvironment provided by the pseudo-DMF moities, the polar HCPs manifested outstanding performances in the conversions of NaN3 to benzylic azides and 1,2,3-triazoles in EtOH (95%), respectively, avoiding the use of risky DMF and improving the separation processes of the products.
- Bai, Rongxian,Gao, Feng,Gu, Yanlong,Li, Minghao
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supporting information
p. 7499 - 7505
(2021/10/12)
-
- DIHYDRO-SPIRO[INDOLINE-3:1'-ISOQUINOLIN]-2-ONES AND THEIR ANALOGUES AND DERIVATIVES AND METHODS OF TREATING CANCER AND OTHER DISEASES
-
The present invention is directed to various 3',4'-dihydro-2'H-spiro[indoline-3:1'-isoquinolin]-2-one compounds and methods for treating disease states and/or conditions which are mediated through sphingosine-1-phosphate receptor(s). The present invention
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-
Page/Page column 48
(2020/09/30)
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- Preparation method of dopamine hydrochloride
-
The invention provides a method which comprises the following steps: taking veratraldehyde as a starting raw material, firstly carrying out condensation reaction with nitromethane to generate 3, 4-dimethoxy-beta-nitrostyrolene, carrying out catalytic reduction to obtain 3, 4-dimethoxy phenylethylamine, carrying out reaction with hydrobromic acid to remove methoxy, and finally salifying with hydrochloric acid to obtain dopamine hydrochloride. The preparation method has the advantages of cheap and easily available initial raw materials, simple process, no high-temperature and high-pressure steps, low cost, high purity and high yield, and is suitable for industrial production.
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-
Paragraph 0035-0038; 0045-0048; 0055-0058; 0065-0068
(2020/11/26)
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- Synthesis, antimicrobial study, and molecular docking simulation of 3,4-dimethoxy-β-nitrostyrene derivatives as candidate ptp1b inhibitor
-
A derivative series of 3,4-dimethoxy-β-nitrostyrene was synthesized through nitroaldol reaction, including a new compound of 3,4-ethylenedioxy-β-bromo-β-nitrostyrene. The antimicrobial activity effect of 3,4-alkyloxy modification of β-nitrostyrene was investigated. A molecular docking study was also performed to obtain information about their interactions with protein tyrosine phosphatase 1B (PTP1B). The active residues of cysteine-215 and arginine-221 of PTP1B play a key role in signaling pathways that regulate various microorganism cell functions. It also acts as a negative regulator in signaling pathways of insulin that are involved in type 2 diabetes and other metabolic diseases. These derivatives exhibited potential antifungal activity. The studied compounds were also had potential as fragments to be PTP1B inhibitors by interacting with serine-216 and arginine-221 residues, according to their molecular docking. 3,4-Ethylenedioxy-β-methyl-β-nitrostyrene was the most successful potential candidate as a PTP1B inhibitor. However, further research is needed to investigate their potential for medicinal use.
- Alfarisi, Salman,Santoso, Mardi,Kristanti, Alfinda Novi,Siswanto, Imam,Puspaningsih, Ni Nyoman Tri
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-
- Combretastatin A-4: The Antitubulin Agent that Inspired the Design and Synthesis of Styrene and Spiroisatin Hybrids as Promising Cytotoxic, Antifungal and Antiviral Compounds
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The design of a series of styrene and spiroisatin hybrids was based on the structure of combretastatin A-4 1. This library of 20 compounds were synthesized with the pharmacophoric units: 3,4,5-trimethoxy or/and 4-hydroxy-3-methoxy phenyl moities in their structure. Thereby, the libraries of β-nitrostyrenes 10a-10c, spiroisatin-dihydroquinolines 14a-14c, spiroisatinthiazolidinones 17a-17c and spiroisatin-nitropyrrolizidines 20a-20k were evaluated for their in vitro cytotoxic, anti-proliferative, antifungal and antiviral activities. Biological results revealed that among these compounds, β-nitrostyrenes 10a-10c exhibited significant cytotoxicity (HeLa and Jurkat tumor cells) and antifungal (T. mentagrophytes) activities. Moreover, the spiroisatin-dihydroquinoline 14a and 14c showed promising cytotoxicity (U937 cells). 14a-14c molecules were active against human herpesviruses serotypes 1 and 2 (HHV-1 and HHV-2), but only 14a and 14b were effective against dengue virus serotype 2 (DENV-2). The spiroisatin-nitropyrrolizidine 20c exhibited moderate anti-herpetic activity, while 17c spiroisatin-thiazolidinone derivative also reduced the infection of HHV-1 and DENV-2. Finally, the molecular docking showed that these kind of molecules interact with the subunit α/β-tubulin.
- Betancur-Galvis, Liliana,Brand, Yaneth M.,Casta?o, Verónica T.,Kouznetsov, Vladimir V.,Linares, Vicky C. R.,Puerto, Carlos E.
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p. 999 - 1010
(2020/10/14)
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- Geometrically Selective Denitrative Trifluoromethylthiolation of β-Nitrostyrenes with AgSCF3for (E)-Vinyl Trifluoromethyl Thioethers
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An efficient copper(II)-promoted denitrative trifluoromethylthiolation under mild reaction conditions has been developed for vinyl trifluoromethyl thioethers to construct Cvinyl-SCF3 bonds with stable AgSCF3 as a source of the trifluoromethylthio. This reaction system tolerates a broad range of functional groups to commendably achieve a high product yield and excellent stereoselectivity of E/Z.
- Fang, Ge,Hong, Jianquan,Huang, Shuai,Jiang, Chao,Liu, Yang,Zhang, Wei,Zheng, Changge
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supporting information
(2020/07/03)
-
- Chlorination of Conjugated Nitroalkenes with PhICl 2and so 2Cl 2for the Synthesis of α-Chloronitroalkenes
-
Chlorination of conjugated nitroalkenes with iodobenzene dichloride or sulfuryl chloride to give target α-chloronitroalkenes in good yields is described. Details of the procedure depend on the donating ability of the nitroalkene substituents. The activity of the described chlorinating agents increases in order 'PhICl 2/Py' 2Cl 2' 2Cl 2/HCl' with the former producing the best yields for highly donating substrates and the latter for non-activated groups. An autocatalytic role of hydrogen chloride and the chemoselectivity of chlorination were also demonstrated.
- Fadeeva, Anastasia A.,Ioffe, Sema L.,Tabolin, Andrey A.
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supporting information
p. 2679 - 2688
(2020/11/02)
-
- NCC Pincer Ni (II) Complexes Catalyzed Hydrophosphination of Nitroalkenes with Diphenylphosphine
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An efficient NCC pincer Ni (II)-catalyzed hydrophosphination of nitroalkenes with diphenylphosphine has been developed. Under the optimized conditions, both (hetero)aromatic and aliphatic nitroalkenes were well tolerated, irrespective of electronic effect, to provide the corresponding products in up to 99% yield.
- Yan, Jing,Wang, Yan-Bing,Hou, Senyao,Shi, Linlin,Zhu, Xinju,Hao, Xin-Qi,Song, Mao-Ping
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-
- Ionic-Liquid Controlled Nitration of Double Bond: Highly Selective Synthesis of Nitrostyrenes and Benzonitriles
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Unprecedented in literature, the conversion of aryl alkenes into β-nitrostyrenes (2) or benzonitriles (3) with sodium nitrite can be governed by an appropriate choice of ionic liquid (IL) medium. A general trend was found for the selectivity of these processes, which depends on the nature of IL, with imidazolium-based ILs, such as [Bmim]Cl, that favor the C–H nitration leading to β-nitrostyrenes, while tetraalkylammonium-based ILs, such as TBAA, privilege the C=C bond cleavage affording benzonitriles. Besides a substrate scope, mechanistic hypotheses were provided on the origin of the different selectivity in the two kinds of ILs, based on their own tunable properties such as polarity, viscosity, and solvent cage effects.
- Casiello, Michele,Caputo, Daniela,Fusco, Caterina,Cotugno, Pietro,Rizzi, Vito,Dell'Anna, Maria Michela,D'Accolti, Lucia,Nacci, Angelo
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supporting information
p. 6012 - 6018
(2020/08/24)
-
- Enantioselective synthesis and anti-parasitic properties of aporphine natural products
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Chagas disease and visceral leishmaniasis are neglected protozoan diseases with significant impact in developing countries. Due to the limited number and toxicity of current therapies, new drug leads are urgently needed. In this work, four aporphine natural products were synthesized using an enantioselective, modular and convergent strategy, comprising eight steps in the longest linear sequence; key steps included Bischler-Napieralski cyclization/Noyori asymmetric reduction to construct the tetrahydroisoquinolines, and palladium-catalyzed arylation to close the C ring. Norglaucine, nordicentrine and dicentrine showed promising bioactivity against T. cruzi and L. infantum, suggesting potential for further development of these scaffolds as antiparasitic agents.
- Amaral, Maiara,Anderson, Edward A.,McHugh, Eliza,Pieper, Pauline,Tempone, Andre G.
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-
- Synthesis of Functionalized Indolines and Dihydrobenzofurans by Iron and Copper Catalyzed Aryl C-N and C-O Bond Formation
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A simple and effective one-pot, two-step intramolecular aryl C-N and C-O bond forming process for the preparation of a wide range of benzo-fused heterocyclic scaffolds using iron and copper catalysis is described. Activated aryl rings were subjected to a highly regioselective, iron(III) triflimide-catalyzed iodination, followed by a copper(I)-catalyzed intramolecular N-or O-arylation step leading to indolines, dihydrobenzofurans, and six-membered analogues. The general applicability and functional group tolerance of this method were exemplified by the total synthesis of the neolignan natural product, (+)-obtusafuran. DFT calculations using Fukui functions were also performed, providing a molecular orbital rationale for the highly regioselective arene iodination process.
- Henry, Martyn C.,Senn, Hans Martin,Sutherland, Andrew
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p. 346 - 364
(2019/01/08)
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- New preparation method of 3,4-dimethoxy-beta-nitrostyrene
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The invention discloses a new preparation method of 3,4-dimethoxy-beta-nitrostyrene and belongs to the technical fields of medicines. The invention aims at relating to a more-advanced new preparationmethod of the 3,4-dimethoxy-beta-nitrostyrene. The new p
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-
Paragraph 0007-0010
(2018/11/03)
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- Green synthesis technology of rotundine sulfate
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The invention provides a green synthesis technology of rotundine sulfate. The green synthesis technology comprises the following steps: firstly, taking pyrocatechol as a starting reactant, and carrying out esterification, acylation and nitration; then carrying out deoxygenation reduction to obtain 3,4-dimethoxyphenethylamine; then carrying out condensation on the obtained 3,4-dimethoxyphenethylamine and 2,3-dimethoxy benzaldehyde and reducing to obtain (3,4-dimethoxy)phenethyl(2,3-dimethoxy)benzylamine; finally, carrying out cyclization, reduction and sulfation on the obtained (3,4-dimethoxy)phenethyl(2,3-dimethoxy)benzylamine, so as to obtain finished-product rotundine sulfate. The invention develops a full-synthesis technology taking the pyrocatechol as a raw material, and provides an environment-friendly, low-cost and high-yield green synthesis technology for synthesizing the rotundine sulfate.
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-
Paragraph 0049; 0051; 0060; 0061; 0062
(2018/09/08)
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- Novel total syntheses of oxoaporphine alkaloids enabled by mild Cu-catalyzed tandem oxidation/aromatization of 1-Bn-DHIQs
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Novel total syntheses of oxoaporphine alkaloids such as liriodenine, dicentrinone, cassameridine, lysicamine, oxoglaucine and O-methylmoschatoline were developed. The key step of these total syntheses is Cu-catalyzed conversion of 1-benzyl-3,4-dihydro-isoquinolines (1-Bn-DHIQs) to 1-benzoyl-isoquinolines (1-Bz-IQs) via tandem oxidation/aromatization. This novel Cu-catalyzed conversion has been studied in detail, and was successfully used for constructing the 1-Bz-IQ core.
- Zheng, Bo,Qu, Hui-Ya,Meng, Tian-Zhuo,Lu, Xia,Zheng, Jie,He, Yun-Gang,Fan, Qi-Qi,Shi, Xiao-Xin
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p. 28997 - 29007
(2018/08/29)
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- Synthesis, antiproliferative and pro-apoptotic effects of nitrostyrenes and related compounds in Burkitt’s lymphoma
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Background: Cancers of the lymphatic cells (lymphomas) account for approximately 12% of malignant diseases worldwide. The nitrostyrene scaffold is identified as a lead target structure for the development of particularly effective compounds targeting Burkitt’s lymphoma (BL). Objectives: The aims of the curent study were to synthesise a panel of nitrostyrene compounds and to evaluate their activity in Burkitt’s lymphoma (BL). Methods: A panel of structurally varied compounds were designed and synthesised using Henry Knoevenagel condensation reactions. Single crystal X-Ray analysis confirmed the E configuration for six examples of these novel structures. A number of nitrostyrene-related compounds were also investigated including 1,3-bis(aryl)-2-nitropropenes together with heterocyclic scaffolds containing the nitrovinyl pharmacophore such as 3-nitro-2-phenyl-2H-chromenes. The antiproliferative activities of the compounds were evaluated using the BL cell lines EBV- MUTU-1 and EBV+ DG-75 (chemoresistant) to establish preliminary structure-activity relationships. Results: Lead compounds with optimized nitrostyrene scaffolds and 3-nitro-2-phenyl-2Hchromene structures were successfully established with typical IC50 values of 0.45 μM and 0.47 μM in MUTU-1 cells and 1.41 μM and 1.92 μM, respectively, in DG-75 cells. The mechanism of cell death was identified as apoptotic and the lead compound was found to elicit comparable apoptotic effects to Taxol in Burkitt’s lymphoma cell lines MUTU-1 and DG-75. Conclusion: This class of pharmaceutically active compounds with potential for the treatment of Burkitt’s lymphoma suggest a potential role for nitrostyrene based agents in chemotherapy.
- Byrne, Andrew J.,Bright, Sandra A.,Fayne, Darren,McKeown, James P.,McCabe, Thomas,Twamley, Brendan,Williams, Clive,Meegan, Mary J.
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p. 181 - 199
(2018/03/13)
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- One-Step, Effective, and Cascade Syntheses of Highly Functionalized Cyclopentenes with High Diastereoselectivity
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Tetrabutylammonium fluoride works as an effective organocatalyst for the cycloaddition between phenacylmalononitriles and electron-deficient olefins (having substituent groups of NO2, CHO, and COR), providing a facile synthetic route to versatile multifunctionalized cyclopentenes having an allylic quaternary carbon center bearing both cyano and carboxamide groups with high yields and high diastereoselectivity. Preliminary studies reveal that these functionalized cyclopentenes are convenient precursors for making α-cyano-functionalized cyclopentadienone oximes.
- Alishetty, Suman,Shih, Hong-Pin,Han, Chien-Chung
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p. 2513 - 2516
(2018/05/17)
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- ZrCl4-mediated synthesis of 1,2,3-triazoles from vinyl nitrates and their biological evaluation
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A ZrCl4-mediated simple method for the conversion of vinyl nitrates to 1,2,3-triazoles in excellent yields is developed. The obtained new triazoles were evaluated for their antimicrobial activity.
- Sridhar, Gattu,Somnath, Mudavath,Sharma, Gangavaram V. M.,Prashanth, Thodupunuri
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p. 551 - 556
(2017/03/15)
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- Design, synthesis and molecular docking study of novel pyrrole-based α-amylase and α-glucosidase inhibitors
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Abstract: In an effort to design and synthesize a new class of α-glucosidase and α-amylase inhibitors, we have synthesized novel pyrrole based molecules using molecular hybridization approach. These novel analogs were synthesized by the novel methodology developed in our lab which comprises of the multi-component direct synthesis route using hypervalent iodine reagent. The compounds were characterized by infrared, 1H nuclear magnetic resonance (NMR), 13C NMR and Mass Spectroscopy. These compounds were screened for their α-amylase and α- glucosidase activity. They showed a varying degree of inhibition with IC50 values ranging between 0.4 to 4.14 μmol/mL and 0.8 to 4.14 μmol/mL for α-amylase and α-glucosidase respectively. Compounds 3, 7, 12, and 18 showed excellent activity as compared to standard acarbose. This has identified a new class of α-amylase and α-glucosidase inhibitor which can be further developed as antihyperglycemic agents. The molecular docking analysis was carried out to better understand of interaction between α-amylase and α-glucosidase target and inhibitors in this series. We also generated a homology model for human α-glucosidase enzyme and identified the key residues at the binding site. The outcome of the study could be used for the rational design of potent and selective α-amylase and α-glucosidase inhibitors, respectively. Graphical abstract: [InlineMediaObject not available: see fulltext.].
- Jadhav, Nikhil C.,Pahelkar, Akshata R.,Desai, Neha V.,Telvekar, Vikas N.
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p. 2675 - 2691
(2017/10/05)
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- Metal-free radical trifluoromethylation of β-nitroalkenes through visible-light photoredox catalysis
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A catalytic method for functional group interconversion is immensely important in modern sciences. Here, we report an efficient catalytic conversion of nitroalkenes to highly stereoselective 1-trifluoromethylalkenes at room temperature. This unprecedented metal-free photocatalytic strategy is simple and operates under visible-light irradiation using the commercially available CF3 source.
- Midya, Siba P.,Rana, Jagannath,Abraham, Thomas,Aswin, Bhaskaran,Balaraman, Ekambaram
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supporting information
p. 6760 - 6763
(2017/07/10)
-
- Multicomponent synthesis of 4-aryl-NH-1,2,3-triazoles in the presence of Al-MCM-41 and sulfated zirconia
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The acid properties of Al-MCM-41 and sulfated zirconia were used to develop a strategy for the synthesis of 4-aryl-NH-1,2,3-triazoles via a multicomponent reaction involving various benzaldehydes, sodium azide and nitromethane. The efficiency of the process is analysed from the perspective of the difference in acids among the catalysts used.
- Vergara-Arenas, Blanca Ivonne,Lomas-Romero, Leticia,ángeles-Beltrán, Deyanira,Negrón-Silva, Guillermo Enrique,Gutiérrez-Carrillo, Atilano,Lara, Víctor Hugo,Morales-Serna, José Antonio
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supporting information
p. 2690 - 2694
(2017/06/23)
-
- Tetraarylphosphonium inner-salts (TAPIS) as both Lewis base catalyst and phase tag
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Tetraarylphosphonium inner-salts (TAPIS) have been designed, synthesized and verified as recyclable and reusable Lewis base catalysts. The resulted TAPIS catalyst has been successfully applied in Michael addition, cyanation and trifluoromethylation reactions.
- Guo, Shuhui,Mi, Xueling
-
supporting information
p. 2881 - 2884
(2017/07/11)
-
- Asymmetric total synthesis of tetrahydroprotoberberine derivatives and evaluation of their binding affinities at dopamine receptors
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Cocaine addiction remains a serious challenge for clinical and medical research because there is no effective pharmacological treatment. L-THP, a natural product isolated from Corydalis yanhusuo W.T. Wang, is one of the most frequently used traditional herbs to treat drug addiction in China. Our laboratory first reported that its demethylated metabolites L-ICP, L-CD, and L-CP had high affinity at dopamine D1, D2, and D5 receptors. Here we report the chemical synthesis of these metabolites and other derivatives and their binding affinities at dopamine receptors. The synthesis of these bioactive metabolites will allow further in vivo study of their potential in treating cocaine addiction.
- Lee, David Y.W.,Liu, Jing,Zhang, Shuzhen,Huang, Peng,Liu-Chen, Lee-Yuan
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p. 1437 - 1440
(2017/03/08)
-
- Fe(III)/Pyridine-Mediated Decarboxylative Nitration of α,β-Unsaturated Acids with Iron Nitrate
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A novel and efficient method for the synthesis of (E)-nitroolefins in moderate to excellent yields is developed by Fe(III)/pyridine-mediated decarboxylative nitration of α,β-unsaturated acids with iron nitrate. A series of α,β-unsaturated acids are well tolerated in this procedure.
- Yang, Zan,Li, Jiao,Hua, Jie,Yang, Tao,Yi, Jianmin,Zhou, Congshan
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supporting information
p. 1079 - 1082
(2017/05/19)
-
- Palladium(II)-catalyzed C-C and C-O bond formation for the synthesis of C1-benzoyl isoquinolines from isoquinoline: N -oxides and nitroalkenes
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C1-Benzoyl isoquinolines can be generated via a palladium(ii)-catalyzed C-C and C-O coupling of isoquinoline N-oxides with aromatic nitroalkenes. The reaction proceeds through remote C-H bond activation and subsequent intramolecular oxygen atom transfer (OAT). In this reaction, the N-O bond was designed as a directing group in the C-H bond activation as well as the source of an oxygen atom.
- Li, Jiu-Ling,Li, Wei-Ze,Wang, Ying-Chun,Ren, Qiu,Wang, Heng-Shan,Pan, Ying-Ming
-
supporting information
p. 10028 - 10031
(2016/08/15)
-
- Therapeutic use of benzylidene tetrahydropyridine derivatives
-
The invention belongs to the technical field of pharmaceutical and relates to therapeutic use of benzylidene tetrahydropyridine derivatives, specifically use of berberine derivatives for resisting diabetes, reducing blood fat and cholesterol, and treating cardiovascular diseases, particularly use of resisting diabetes.
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-
Paragraph 0024
(2017/03/21)
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- Iron-Mediated One-Pot Synthesis of 3,5-Diarylpyridines from β-Nitrostyrenes
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An operationally simple and mild one-pot protocol for the synthesis of a variety of 3,5-diarylpyridines from β-nitrostyrenes was achieved by using elemental iron. This reaction proceeds via reduction of the nitro group, resulting in in situ imine formation followed by trimolecular condensation with concomitant debenzylative aromatization. By employing this method, a series of symmetrical and unsymmetrical 3,5-diarylpyridines were synthesized with good to excellent yields. In addition, this method was also utilized for the synthesis of Sch-21418, an anti-inflammatory agent on gram scale.
- Sathish, Manda,Chetna, Jadala,Hari Krishna, Namballa,Shankaraiah, Nagula,Alarifi, Abdullah,Kamal, Ahmed
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p. 2159 - 2165
(2016/03/15)
-
- Enhanced copper-mediated 18F-fluorination of aryl boronic esters provides eight radiotracers for PET applications
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[18F]FMTEB, [18F]FPEB, [18F]flumazenil, [18F]DAA1106, [18F]MFBG, [18F]FDOPA, [18F]FMT and [18F]FDA are prepared from the corresponding arylboronic esters and [18
- Preshlock, Sean,Calderwood, Samuel,Verhoog, Stefan,Tredwell, Matthew,Huiban, Mickael,Hienzsch, Antje,Gruber, Stefan,Wilson, Thomas C.,Taylor, Nicholas J.,Cailly, Thomas,Schedler, Michael,Collier, Thomas Lee,Passchier, Jan,Smits, René,Mollitor, Jan,Hoepping, Alexander,Mueller, Marco,Genicot, Christophe,Mercier, Jo?l,Gouverneur, Véronique
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supporting information
p. 8361 - 8364
(2016/07/07)
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- Diaminosilane-functionalized on silicate-stabilised hydrotalcite (MA-HTSi-DA): As potential catalyst for nitro-aldol condensation
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Diaminosilane was introduced into silicate-anion-intercalated hydrotalcite (HT-Si) using a post-synthesis method. The resulting functionalized materials possess surface basicity. The textural properties of the functionalized materials were systematically investigated through powder XRD, FTIR and MAS-NMR studies. The diamine-functionalized materials showed very good catalytic activity for the nitro-aldol condensation of benzaldehyde and nitromethane under solvent-free conditions. The materials showed comparable catalytic activity upon recycling.
- Thangaraj, Baskaran,Jayaraj, Christopher,Srinivasan, Radhakrishnan,Ayyamperumal, Sakthivel
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- Ethylenediamine-functionalized magnetic Fe3O4@SiO2 nanoparticles: cooperative trifunctional catalysis for selective synthesis of nitroalkenes
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A magnetically separable trifunctional nanocatalyst Fe3O4@SiO2-NH2 was synthesized and characterized by TEM, FT-IR, XRD, TGA, and EA. The designed nanocatalyst was found to be highly active for selective synthesis of nitroalkenes with nitromethane and aromatic aldehyde through cooperative trifunctional catalysis of primary amine, secondary amine and Si-OH groups on the surface of the catalyst. Under the optimized conditions, various representative substrates were extended to obtain the corresponding products in moderate or excellent yields. After the reaction, the trifunctional nanocatalyst was easily recovered and recycled by applying an external magnet. In addition, a possible cooperative trifunctional catalysis mechanism was also proposed.
- Xue, Fengjun,Dong, Yahao,Hu, Peibo,Deng, Yanan,Wei, Yuping
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p. 73684 - 73691
(2015/09/15)
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- Iodine catalyzed one-pot synthesis of highly substituted N-methyl pyrroles via [3 + 2] annulation and their in vitro evaluation as antibacterial agents
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A new class of highly substituted pyrroles have been synthesized via a simple, fast, and efficient method using environmentally friendly iodine catalyzed [3 + 2] annulation. N-Methyl-N-[(E)-1-(methylsulfanyl)-2-nitro-1-ethenyl]amine (NMSM) 1 and β-nitrostyrenes 3 underwent cycloaddition to afford the desired products 4 in excellent yields under solvent and metal free conditions. All the pyrrole derivatives were evaluated for their in vitro anti-bacterial activity. Among the synthesized pyrrole derivatives, 4b, 4c, 4e, 4g, 4i, 4j, 4l, 4m and 4n displayed good inhibitory properties against a panel of Gram positive and negative infectious pathogens.
- Balachandra, Biguvu,Shanmugam, Sivakumar,Muneeswaran, Thillaichidambaram,Ramakritinan, Muthiah
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p. 64781 - 64789
(2015/08/18)
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- Synthesis of β-nitrostyrenes in the presence of sulfated zirconia and secondary amines
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A simple and efficient protocol for the synthesis of β-nitrostyrenes has been achieved by the use of sulfated zirconia-secondary amine (piperidine, pyrrolidine, proline or prolinol) cooperative systems. The condensation of different aldehydes and nitromethane demonstrates the efficiency of this process, which does not require high-temperature reactivation for the reuse of the catalytic material.
- González-Olvera,Vergara-Arenas,Negrón-Silva,Angeles-Beltrán,Lomas-Romero,Gutiérrez-Carrillo,Lara,Morales-Serna
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p. 99188 - 99192
(2015/12/05)
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- Mild and efficient reductive deoxygenation of epoxides to olefins with tin(II) chloride/sodium iodide as a novel reagent
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A highly efficient and green protocol is reported for the reductive deoxygenation of organic epoxides to olefins using tin(II) chloride/sodium iodide as a novel reagent. The reaction gives an excellent yield (85-96%) in ethanol under reflux within 2-10 minutes, without affecting other functional groups. The advantages of our method are the use of inexpensive reagents, the eco-friendly and green reaction conditions, and the short reaction times and high yields.
- Pathe, Gulab Khushalrao,Ahmed, Naseem
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supporting information
p. 3542 - 3552
(2015/11/17)
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- 17a-HYDROXYLASE/C17,20-LYASE INHIBITORS
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The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, A and n are as defined herein. A deuteriated derivative of the compound of Formula (I) is also provided.
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Paragraph 0692
(2014/03/21)
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- Chemoselective zinc/HCl reduction of halogenated β-nitrostyrenes: Synthesis of halogenated dopamine analogues
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A detailed account regarding the synthesis of 2- and 5-halogenated dopamine is given. The key step is a chemoselective reduction of a nitrostyrene by Zn/HCl at 0 °C. These conditions represent a simple, low-cost alternative to reduction by water-sensitive hydride donors and two-step procedures. Under these conditions, aryl fluoride, chloride, and bromide groups are stable. However, iodine undergoes significant reductive dehalogenation.
- Maresh, Justin J.,Ralko, Arthur A.,Speltz, Tom E.,Burke, James L.,Murphy, Casey M.,Gaskell, Zachary,Girel, Joann K.,Terranova, Erin,Richtscheidt, Conrad,Krzeszowiec, Mark
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supporting information
p. 2891 - 2894
(2015/02/02)
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- Unusual reactivity of nitronates with an aryl alkyl carbonate: Synthesis of α-amino esters
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The monoanions of nitroalkanes are ambident nucleophiles that react with carbonate electrophiles through the oxygen atom. Products arising from reactivity at the carbon atom will yield α-nitro esters, which are precursors for α-amino esters. We demonstrate this in the reactions of nitroalkanes with benzyl phenyl carbonate and DABCO where α-nitro esters are obtained instead of nitrile oxides. The products are readily reduced to α-amino esters. This pathway could be a safe alternative to the Strecker reaction.
- Reddy, Golipalli Ramana,Mukherjee, Debopreeti,Chittoory, Arjun Kumar,Rajaram, Sridhar
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supporting information
p. 5874 - 5877
(2015/01/08)
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- Synthesis, in vitro cytotoxicity and apoptosis inducing study of 2-aryl-3-nitro-2 H -chromene derivatives as potent anti-breast cancer agents
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A series of 2-aryl-3-nitro-2H-chromenes 4a-u were designed as hybrid analogs of flavanone, β-nitrostyrene and nitrovinylstilbene scaffolds. They were synthesized from the reaction of appropriate β-nitrostyrenes and salicylaldehydes in good yields. In vitro cytotoxic activities of compounds 4a-u were tested against breast cancer cell lines including MCF-7, T-47D and MDA-MB-231. Most compounds exhibited good cytotoxic activity against selected cell lines, being more potent than standard drug etoposide. Representatively, 8-methoxy-3-nitro-2-(4-chlorophenyl)-2H-chromene (4l) with IC50 Combining double low line 0.2 μ4M against MCF-7 cells, was 36-times more potent than etoposide. Apoptosis as a mechanism of cell death for selected compounds 4h and 4l was confirmed morphologically by acridine orange/ethidium bromide double staining and TUNEL analysis, as well as caspase-3 activation assay.
- Rahmani-Nezhad, Samira,Safavi, Maliheh,Pordeli, Mahboobeh,Ardestani, Sussan Kabudanian,Khosravani, Leila,Pourshojaei, Yaghoub,Mahdavi, Mohammad,Emami, Saeed,Foroumadi, Alireza,Shafiee, Abbas
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p. 562 - 569
(2015/01/09)
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- PhICl2 and wet DMF: An efficient system for regioselective chloroformyloxylation/a-chlorination of alkenes/a,β-unsaturated compounds
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PhICl2 in wet DMF was found to form an efficient system for realizing difunctionalization of various alkenes and olefinic derivatives possessing a wide range of functional groups. This novel methodology provides convenient access to either regioselective chloroformyloxylated products or a-chlorinated olefinic products, depending on the type of structure of the original unsaturated starting material. The mechanism of the reaction is proposed and discussed.
- Liu, Le,Zhang-Negrerie, Daisy,Du, Yunfei,Zhao, Kang
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supporting information
p. 436 - 439
(2014/04/03)
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- Asymmetric total synthesis and identification of tetrahydroprotoberberine derivatives as new antipsychotic agents possessing a dopamine D1, D2 and serotonin 5-HT1A multi-action profile
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An effective and rapid method for the microwave-assisted preparation of the key intermediate for the total synthesis of tetrahydroprotoberberines (THPBs) including l-stepholidine (l-SPD) was developed. Thirty-one THPB derivatives with diverse substituents on A and D ring were synthesized, and their binding affinity to dopamine D1, D2 and serotonin 5-HT 1A and 5-HT2A receptors were determined. Compounds 18k and 18m were identified as partial agonists at the D1 receptor with Ki values of 50 and 6.3 nM, while both compounds act as D2 receptor antagonists (Ki = 305 and 145 nM, respectively) and 5-HT1A receptor full agonists (Ki = 149 and 908 nM, respectively). These two THPBs compounds exerted antipsychotic actions in animal models. Further electrophysiological studies employing single-unit recording in intact animals demonstrated that 18k-excited dopaminergic (DA) neurons are associated with its 5-HT1A receptor agonistic activity. These results suggest that these two compounds targeted to multiple neurotransmitter receptors may present novel lead drugs with new pharmacological profiles for the treatment of schizophrenia.
- Sun, Haifeng,Zhu, Liyuan,Yang, Huicui,Qian, Wangke,Guo, Lin,Zhou, Shengbin,Gao, Bo,Li, Zeng,Zhou, Yu,Jiang, Hualiang,Chen, Kaixian,Zhen, Xuechu,Liu, Hong
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supporting information
p. 856 - 868
(2013/03/13)
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- A branched domino reaction: Asymmetric organocatalytic two-component four-step synthesis of polyfunctionalized cyclohexene derivatives
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Take two: By employing two equivalents of an aldehyde in an asymmetric organocatalytic domino reaction, the nucleophilic enamine intermediate is also converted into the corresponding iminium species through oxidation with o-iodoxybenzoic acid. Thus, polyfunctionalized cyclohexene derivatives are formed from two simple starting materials in good yields and stereoselectivities (see scheme; Bn=benzyl, EWG=electron-withdrawing group). Copyright
- Zeng, Xiaofei,Ni, Qijian,Raabe, Gerhard,Enders, Dieter
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supporting information
p. 2977 - 2980
(2013/04/11)
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- Synthesis of substituted nitroolefins: A copper catalyzed nitrodecarboxylation of unsaturated carboxylic acids
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A novel, mild and convenient method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their nitroolefins is achieved using a catalytic amount of CuCl (10 mol%) and tert-butyl nitrite (2 equiv.) as a nitrating agent in the presence of air. This reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives, which are generally difficult to access from other conventional methods. Additionally, this reaction is selective as the E-isomer of the acid derivatives furnishes the corresponding E-nitroolefins. One more salient feature of the method is, unlike other methods, no metal nitrates or HNO3 are employed for the transformation.
- Rokade, Balaji V.,Prabhu, Kandikere Ramaiah
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p. 6713 - 6716
(2013/10/01)
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- Synthesis of nitroalkenes involving a cooperative catalytic action of iron(III) and piperidine: A one-pot synthetic strategy to 3-alkylindoles, 2H-chromenes and N-arylpyrrole
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An efficient and simple strategy has been developed to synthesize various substituted nitroalkenes involving a cooperative catalytic system of FeCl 3 and piperidine. This dual catalytic protocol simultaneously activates both electrophile and nucleophile and works under mild reaction conditions so that many sensitive functional groups were tolerated. Moreover, this cooperative catalytic reaction is also suitable for various one-pot reactions involving nitroalkenes such as, 2H-chromenes, N-arylpyrrole and Michael reaction with indole. Notably, this method is low-cost, efficient and environmentally friendly. Copyright
- Jalal, Swapnadeep,Sarkar, Soumen,Bera, Krishnendu,Maiti, Sukhendu,Jana, Umasish
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supporting information
p. 4823 - 4828
(2013/08/23)
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- Design, synthesis, and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists
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The synthesis of a new series of Erythrina alkaloid analogues and their pharmacological characterization at various nicotine acetylcholine receptor (nAChR) subtypes are described. The compounds were designed to be simplified analogues of aromatic erythrinanes with the aim of obtaining subtype-selective antagonists for the nAChRs and thereby probe the potential of using these natural products as scaffolds for further ligand optimization. The most selective and potent nAChR ligand to come from the series, 6,7-dimethoxy-2- methyl-1,2,3,4-tetrahydroisoquinoline (3c) (also a natural product by the name of O-methylcorypalline), displayed submicromolar binding affinity toward the α4β2 nAChR with more than 300-fold selectivity over α4β4, α3β4, and α7. Furthermore, this lead structure (which also has inhibitory activity at monoamine oxidases A and B and at the serotonin and norepinephrine transporters) showed antidepressant-like effect in the mouse forced swim test at 30 mg/kg.
- Crestey, Fran?ois,Jensen, Anders A.,Borch, Morten,Andreasen, Jesper Tobias,Andersen, Jacob,Balle, Thomas,Kristensen, Jesper Langgaard
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supporting information
p. 9673 - 9682
(2014/01/06)
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- Regio- and stereoselective synthesis of spirooxindole 1′-nitro pyrrolizidines with five concurrent stereocenters under aqueous medium and their bioprospection using the zebrafish (Danio rerio) embryo model
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A highly regio- and stereoselective method has been developed and expanded for the synthesis of a 20-membered library of spirooxindole 1′-nitro pyrrolizidines via 1,3-dipolar cycloaddition of azomethine ylides, generated in situ by a decarboxylative route from a common set of diverse isatins and l-proline derivatives, with substituted β-nitrostyrenes under aqueous medium. Among various reaction conditions, water proved to be necessary for the interaction of the reagents as well as heating the reaction at 90 °C for one hour, during which time the desired products were obtained in good yields and with excellent regio- and stereoselectivities. We subsequently applied in silico drug discovery computational methods to (i) identify the ADME properties, based on Lipinski's rule, (ii) screen the toxicological profile, and (iii) predict the penetration through the blood brain barrier (BBB) of the synthesized compounds. Next, the LC50 values of all these spirocyclic oxindoles were determined in zebrafish embryos cultured individually in buffer solutions of each compound and, finally, the phenotypes induced by these molecules in the zebrafish embryos at concentrations below their LC50 were analyzed at 48, 72 and 96 hours post fertilization.
- Puerto Galvis, Carlos E.,Kouznetsov, Vladimir V.
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p. 7372 - 7386
(2013/10/22)
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- Direct Henry reactions with modified calcium oxide as solid catalyst
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Commercial CaO was modified simply with benzyl bromide. The modified CaO had good water resistance, and characterization by FTIR and TG revealed the modifier was chemically bonded to the CaO surface. Commercial CaO and CaO modified with benzyl bromide were investigated as catalysts for the Henry reaction between benzaldehyde and nitromethane. It was found that the catalytic activity of the modified CaO was greatly improved, with high conversion of benzaldehyde to the (E)-phenyl nitroolefin and 1-phenyl-2-nitroethanol, and with different selectivity from commercial CaO. The effect of modification and reaction conditions on yield, selectivity, and mechanism were studied thoroughly.
- Tang, Ying,Gu, Xuefan,Meng, Mei,Xu, Jingfang
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p. 3715 - 3725
(2013/10/22)
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- One-pot solid phase synthesis of (E)-nitroalkenes
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An efficient one-pot protocol for the synthesis of (E)-nitroalkenes by reaction of aldehydes and nitroalkanes in the presence of polymer-bound triphenylphosphine, iodine and imidazole is described. Although the reaction works with similar efficiency with triphenylphosphine and its polymer-bound version, easy removal of the unwanted polymer-bound triphenylphosphine oxide and its recovery as triphenylphosphine provide the edge for practical application of the method.
- Rokhum, Lalthazuala,Bez, Ghanashyam
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p. 5500 - 5504
(2013/09/23)
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