- H2O2-mediated room temperature synthesis of 2-arylacetophenones from arylhydrazines and vinyl azides in water
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An environmentally benign, cost-efficient and practical methodology for the room temperature synthesis of 2-arylacetophenones in water has been discovered. The facile and efficient transformation involves the oxidative radical addition of arylhydrazines with α-aryl vinyl azides in the presence of H2O2 (as a radical initiator) and PEG-800 (as a phase-transfer catalyst). From the viewpoint of green chemistry and organic synthesis, the present protocol is of great significance because of using cheap, non-toxic and readily available starting materials and reagents as well as amenability to gram-scale synthesis, which provides an attractive strategy to access 2-arylacetophenones.
- Luo, Mengqiang,Zhang, Yaohong,Fang, Ping,Li, Yan,Qi, Chenze,Li, Yong,Shen, Runpu,Cheng, Kai,Wang, Hai
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supporting information
p. 630 - 635
(2022/02/01)
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- Oxaprozin Analogues as Selective RXR Agonists with Superior Properties and Pharmacokinetics
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The retinoid X receptors (RXR) are ligand-activated transcription factors involved in multiple regulatory networks as universal heterodimer partners for nuclear receptors. Despite their high therapeutic potential in many pathologies, targeting of RXR has only been exploited in cancer treatment as the currently available RXR agonists suffer from exceptional lipophilicity, poor pharmacokinetics (PK), and adverse effects. Aiming to overcome the limitations and to provide improved RXR ligands, we developed a new potent RXR ligand chemotype based on the nonsteroidal anti-inflammatory drug oxaprozin. Systematic structure-activity relationship analysis enabled structural optimization toward low nanomolar potency similar to the well-established rexinoids. Cocrystal structures of the most active derivatives demonstrated orthosteric binding, and in vivo profiling revealed superior PK properties compared to current RXR agonists. The optimized compounds were highly selective for RXR activation and induced RXR-regulated gene expression in native cellular and in vivo settings suggesting them as excellent chemical tools to further explore the therapeutic potential of RXR.
- Schierle, Simone,Chaikuad, Apirat,Lillich, Felix F.,Ni, Xiaomin,Woltersdorf, Stefano,Schallmayer, Espen,Renelt, Beatrice,Ronchetti, Riccardo,Knapp, Stefan,Proschak, Ewgenij,Merk, Daniel
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supporting information
p. 5123 - 5136
(2021/05/04)
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- Visible-Light-Promoted [3 + 2] Cycloaddition of 2H-Azirines with Quinones: Access to Substituted Benzo[f]isoindole-4,9-diones
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A visible-light-promoteded [3 + 2] cycloaddition reaction of 2H-azirines with quinones has been developed under mild reaction conditions. The reaction provides a general and efficient strategy for the synthesis of the benzo[f]isoindole-4,9-diones scaffold
- Li, Lei,Liu, Chuang,Sun, Ran,Wang, He,Wang, Lijia,Wang, Xin,Zhou, Ming-Dong
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supporting information
(2022/01/22)
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- Palladium-catalyzed synthesis of α-aryl acetophenones from styryl ethers and aryl diazonium saltsviaregioselective Heck arylation at room temperature
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Preparation of α-aryl acetophenones from styryl ethers and aryldiazonium salts is described. The reaction is catalyzed by palladium acetate at room temperature in the absence of ligand and base. The developed method is highly attractive in terms of reaction conditions, substrate scope, functional group tolerance and yields. Synthetic applications of the present method are demonstrated by preparing α-aryl indoles and 3-aryl isocoumarin from styryl ethers.
- Kandasamy, Jeyakumar,Lee, Yong Rok,Singh, Adesh Kumar,Venkatesh, Rapelly
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supporting information
p. 7832 - 7837
(2021/09/28)
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- Fukuyama Cross-Coupling Approach to Isoprekinamycin: Discovery of the Highly Active and Bench-Stable Palladium Precatalyst POxAP
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An efficient and user-friendly palladium(II) precatalyst, POxAP (post-oxidative-addition precatalyst), was identified for use in Fukuyama cross-coupling reactions. Suitable for storage under air, the POxAP precatalyst allowed reaction between thioesters and organozinc reagents with turnover numbers of ~90000. A series of 23 ketones were obtained with yields ranging from 53 to 99%. As proof of efficacy, an alternative approach was developed for the synthesis of a key precursor of the natural product isoprekinamycin.
- Tang, Shuang-Qi,Bricard, Jacques,Schmitt, Martine,Bihel, Frédéric
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p. 844 - 848
(2019/01/30)
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- Discovery of the First in Vivo Active Inhibitors of the Soluble Epoxide Hydrolase Phosphatase Domain
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The emerging pharmacological target soluble epoxide hydrolase (sEH) is a bifunctional enzyme exhibiting two different catalytic activities that are located in two distinct domains. Although the physiological role of the C-terminal hydrolase domain is well-investigated, little is known about its phosphatase activity, located in the N-terminal phosphatase domain of sEH (sEH-P). Herein we report the discovery and optimization of the first inhibitor of human and rat sEH-P that is applicable in vivo. X-ray structure analysis of the sEH phosphatase domain complexed with an inhibitor provides insights in the molecular basis of small-molecule sEH-P inhibition and helps to rationalize the structure-activity relationships. 4-(4-(3,4-Dichlorophenyl)-5-phenyloxazol-2-yl)butanoic acid (22b, SWE101) has an excellent pharmacokinetic and pharmacodynamic profile in rats and enables the investigation of the physiological and pathophysiological role of sEH-P in vivo.
- Kramer, Jan S.,Woltersdorf, Stefano,Duflot, Thomas,Hiesinger, Kerstin,Lillich, Felix F.,Kn?ll, Felix,Wittmann, Sandra K.,Klingler, Franca-M.,Brunst, Steffen,Chaikuad, Apirat,Morisseau, Christophe,Hammock, Bruce D.,Buccellati, Carola,Sala, Angelo,Rovati, G. Enrico,Leuillier, Matthieu,Fraineau, Sylvain,Rondeaux, Julie,Hernandez-Olmos, Victor,Heering, Jan,Merk, Daniel,Pogoryelov, Denys,Steinhilber, Dieter,Knapp, Stefan,Bellien, Jeremy,Proschak, Ewgenij
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p. 8443 - 8460
(2019/10/16)
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- Mn/Cu catalyzed addition of arylboronic acid to nitriles: Direct synthesis of arylketones
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A direct and efficient synthesis of arylketones via arylboronic acid addition to nitriles in presence of inexpensive Mn/Cu catalytic system is reported. The use of non-precious Mn and Cu salts has been found to be highly advantageous both in terms of accessibility as well as cost effectiveness. A series of arylboronic acids as well as nitriles were used to synthesize a variety of symmetrical and unsymmetrical arylketones. Based on the literature studies, the reaction mechanism is anticipated to go through an aryl radical intermediate which reacted with the copper activated nitrile to give the desired arylketones after the hydrolysis of the imine intermediate.
- Moustafa, Dina,Sweet, Chelsea,Lim, Hyun,Calalpa, Brenda,Kaur, Parminder
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p. 3816 - 3820
(2018/09/18)
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- Coupling of Sulfoxonium Ylides with Arynes: A Direct Synthesis of Pro-Chiral Aryl Ketosulfoxonium Ylides and Its Application in the Preparation of α-Aryl Ketones
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A general, mild, and versatile synthesis of the challenging α-aryl-β-ketosulfoxonium ylides has been developed for the first time, substituting traditional methods starting from diazo compounds. The arylation of easily accessible β-ketosulfoxonium ylides using aryne chemistry allowed the preparation of a large scope of the pro-chiral ylides in very good yields (40 examples; up to 85%). As applications, these ylides were smoothly converted into α-aryl ketones after desulfurization in good yields (up to 98%) as well as in other important derivatives.
- Talero, Alexánder Garay,Martins, Bruna Sim?es,Burtoloso, Antonio C. B.
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supporting information
p. 7206 - 7211
(2018/11/23)
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- Metal-free synthesis of ketones by visible-light induced aerobic oxidative radical addition of aryl hydrazines to alkenes
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A green and cost-effective method has been developed for the conversion of alkenes to ketones under metal-free conditions. The reaction involves the oxidative addition of alkenes with aryl radicals, which are generated by visible-light induced aerobic oxidation of arylhydrazines. The key features of this reaction include broad substrate scope, readily available reagents and amenability to gram-scale synthesis.
- Ding, Ya,Zhang, Wenkai,Li, Hao,Meng, Yunge,Zhang, Te,Chen, Qiu-Yun,Zhu, Chunyin
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supporting information
p. 2941 - 2944
(2017/07/24)
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- An unusual chemoselective oxidation strategy by an unprecedented exploration of an electrophilic center of DMSO: A new facet to classical DMSO oxidation
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A conceptually new dimethyl sulfoxide (DMSO) based oxidation process without the use of any activator has been demonstrated for the oxidation of active methylenes and benzhydrols. The developed protocol utilizes the electrophilic center of DMSO for oxidation, which was unexplored before. Mechanistic investigation has confirmed that the source of oxygen is DMSO.
- Chebolu, Rajesh,Bahuguna, Ashish,Sharma, Reena,Mishra, Vivek Kumar,Ravikumar
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p. 15438 - 15441
(2015/10/20)
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- ISOXAZOLE DERIVATIVES USED AS OESTROGEN MODULATORS
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The present invention relates to a substituted isoxazole derivative according to formula (I), wherein the variables are defined as in the specification, or to a pharmaceutically acceptable salt, solvate or prodrug thereof. The present invention also relates to a pharmaceutical composition comprising said substituted isoxazole derivatives and to their use as a contraceptive or in therapy, for instance in the treatment or prevention of estrogen-receptor mediated disorders or estrogen-receptor related physiological conditions such as climacteric disorders and osteoporosis.
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Page/Page column 31
(2012/05/05)
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- Polyaniline-supported zinc oxide (ZnO) nanoparticles: An active and stable heterogeneous catalyst for the Friedel-Crafts acylation reaction
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We report herein the synthesis of zinc oxide (ZnO) nanoparticles incorporating a polyaniline (PANI) matrix in aqueous medium and its catalytic performance toward Friedel-Crafts acylation reactions. The acylation reactions demonstrate that polyaniline/ nano-ZnO composites are very active catalysts and are able to activate the reactant at ambient temperature. The obtained nanocatalyst was characterized by Fourier transform-infrared, scanning electron microscopy, transmission electron microscopy, Brunauer-Emmett-Teller, X-ray diffraction, and particle-size analysis techniques. The catalyst was reusable for five cycles without appreciable loss in activity. Copyright Taylor & Francis Group, LLC.
- Rezaei, Seyed Jamal Tabatabaei,Nabid, Mohammad Reza,Hosseini, Seyedeh Zahra,Abedi, Mahvash
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experimental part
p. 1432 - 1444
(2012/04/17)
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- Palladium-catalyzed carbonylative coupling of benzyl chlorides with aryl boronic acids in aqueous media
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A novel chemoselective protocol for the carbonylative Suzuki coupling of benzyl chlorides with aryl boronic acids at low pressure of carbon monoxide has been developed. Applying a commercially available palladium acetate/PCy 3 catalyst system in the presence of potassium phosphate as the base and water as the solvent the coupling reactions proceeded smoothly. To demonstrate the general applicability 12 different α-arylated acetophenones have been synthesized in moderate to good yields (41-78%) under mild conditions.
- Wu, Xiao-Feng,Neumann, Helfried,Beller, Matthias
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experimental part
p. 6146 - 6149
(2010/12/24)
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- Diverse alkanones by catalytic carbon insertion into the formyl C-H bond. Concise access to the natural precursor of achyrofuran
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Over a century ago, the first reactions of diazomethane with aldehydes delivered methyl ketones. In the interim, aldehydes have been homologated with trimethylsilyldiazomethane, diazoacetates, and aryldiazomethanes, on rare occasion with catalysis. This work describes a mild procedure for convergent ketone assembly from nonstabilized diazoalkanes, including examples of chiral ketone synthesis with disubstituted (internal) nucleophiles. The method's remarkable tolerance to steric crowding is showcased in a simple approach to achyrofuran, a complex dibenzofuran.
- Wommack, Andrew J.,Moebius, David C.,Travis, Austin L.,Kingsbury, Jason S.
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supporting information; experimental part
p. 3202 - 3205
(2009/11/30)
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- TiCl4-catalyzed indirect anti-Markovnikov hydration of alkynes: Application to the synthesis of benzo[b]furans
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(Chemical Equation Presented) An efficient methodology for the indirect anti-Markovnikov hydration of unsymmetrically substituted terminal and internal alkynes is based on TiCl4-catalyzed hydroamination reactions. Its application to ortho-alkynylhaloarenes, followed by a copper-catalyzed O-arylation, provides flexible access to substituted benzo[b]furans.
- Ackermann, Lutz,Kaspar, Ludwig T.
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p. 6149 - 6153
(2008/02/09)
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- THERAPEUTIC FLUOROETHYL UREAS
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Compounds of the formula or a pharmaceutically acceptable salt thereof or a tautomer thereof, wherein A and B are as described herein, are useful for treating conditions afflicting mammals.
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Page/Page column 14
(2008/06/13)
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- Synthesis of 4H-benzo[e]-1,2-selanazin-4-one derivatives: a new heterocyclic ring system
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The synthesis of novel 1,2-benzoselenazin-4-ones which are six-membered homologues of ebselen, is described in order to evaluate their glutathione peroxidase-like activity.
- Messali, Mouslim,Christiaens, Léon E.,Alshahateet, Solhe F.,Kooli, Fethi
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p. 7448 - 7451
(2008/03/13)
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- Synthetic Uses of Open-Chain Analogues of Reissert Compounds
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Open-chain analogues, 2, of Reissert compounds are readily obtained by reaction of cyanohydrins with primary amines, the resulting aminonitriles, 1, then being acylated.Hydrofluoroborate salts, 3, of 2 are prepared by reaction with fluoroboric acid in glacial acetic acid.The salts, 3, undergo 1,3-dipolar addition reactions with reactive alkynes to give substituted pyrroles and with ethyl acrylate to give a different type of substituted pyrrole, the initial step in this instance being a Diels-Alder reaction.The open-chain Reissert analogues 2 also undergo base-catalyzed reactions, such as alkylation to provide compounds 22, which, in turn, undergo cleavage reactions in ethanolic alkali to give ketones 23.A conjugate addition reaction of the anion 18 to methyl acrylate to give, after some subsequent steps, a substituted pyrrole, 9, has also been demonstrated. α-Anilino ketones 27 result when the anion 18 is caused to react with aldehydes, the initial reaction mixtures being subjected to subsequent alkaline hydrolysis.Finally, N-benzyl Reissert analogues have been found to give desoxybenzoins plus benzonitriles on treatment with sodium hydride in tetrahydrofuran.
- McEwen, William E.,Grossi, Anthony V.,MacDonald, Russell J.,Stamegna, Andrew P.
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p. 1301 - 1308
(2007/10/02)
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