- Enantioselective Synthesis of Trifluoromethyl α,β-Unsaturated δ-Lactones via Vinylogous Aldol-Lactonization Cascade
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The novel vinylogous aldol-lactonization cascade of alkylidene oxindole with trifluoromethyl ketones is presented. The reaction, catalyzed by a bifunctional tertiary amine, provides an efficient application of the vinylogous reactivity of alkylidene oxindoles for the preparation of enantioenriched trifluoromethylated α,β-unsaturated δ-lactones.
- Crotti, Simone,Di Iorio, Nicola,Mazzanti, Andrea,Righi, Paolo,Bencivenni, Giorgio
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- Palladium-catalyzed carbonylative coupling of aryl iodides with an organocopper reagent: A straightforward procedure for the synthesis of aryl trifluoromethyl ketones
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A palladium-catalyzed carbonylative coupling of aryl iodides with a (trifluoromethyl)copper reagent has been developed. A wide range of substrates have been transformed into their corresponding trifluoromethyl ketones in good to excellent yields under mild conditions with high efficiency and excellent functional-group compatibility. Preliminary mechanistic investigations suggest that the transmetallation of an acylpalladium intermediate with the (trifluoromethyl)copper reagent seems to be involved in the catalytic cycle. Notably, this report represents one of the few studies on carbonylative coupling with organocopper reagents.
- Zhu, Fengxiang,Yang, Guangfu,Zhou, Shaolin,Wu, Xiao-Feng
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Read Online
- Direct Synthesis of Tri-/Difluoromethyl Ketones from Carboxylic Acids by Cross-Coupling with Acyloxyphosphonium Ions
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A simple and straightforward approach to the synthesis of trifluoromethyl and difluoromethyl ketones from widely available carboxylic acids is disclosed. The transformation utilizes an acyloxyphosphonium ion as the active electrophile, conveniently generated in situ from the carboxylic acid substrate by using commodity chemicals. The utility of the reaction system is exemplified by its chemoselectivity, with tolerance to a variety of important functional groups. The late-stage functionalization of carboxylic acid active pharmaceutical ingredients and pharmaceutically relevant compounds is also discussed.
- Ispizua-Rodriguez, Xanath,Munoz, Socrates B.,Krishnamurti, Vinayak,Mathew, Thomas,Prakash
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supporting information
p. 15908 - 15913
(2021/10/07)
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- Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system
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A straightforward method that enables the formation of biologically attractive trifluoromethyl ketones from readily available methyl esters using the potent greenhouse gas fluoroform (HCF3, HFC-23) was developed. The combination of fluoroform and KHMDS in triglyme at ?40 °C was effective for this transformation, with good yields as high as 92%. Substrate scope of the trifluoromethylation procedure was explored for aromatic, aliphatic, and conjugated methyl esters. This study presents a straightforward trifluoromethylation process of various methyl esters that convert well to the corresponding trifluoromethyl ketones. The tolerance of various pharmacophores under the reaction conditions was also explored.
- Fujihira, Yamato,Liang, Yumeng,Ono, Makoto,Hirano, Kazuki,Kagawa, Takumi,Shibata, Norio
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supporting information
p. 431 - 438
(2021/03/20)
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- Highly enantioselective construction of CF3-bearing all-carbon quaternary stereocenters: Hiral spiro-fused bisoxazoline ligands with 1,1′-binaphthyl sidearm for asymmetric Michael-type Friedel-Crafts reaction
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A novel class of chiral spiro-fused bisoxazoline ligands possessing a deep chiral pocket was prepared. The developed ligands have been employed in the nickel-catalyzed highly enantioselective Michael-type Friedel-Crafts reaction, affording the products bearing a trifluoromethylated all-carbon quaternary stereocenter with moderate to excellent yields (up to 99%) and good to excellent enantioselectivies (up to > 99.9% ee). Moreover, a proposed model of chiral pocket revealed that the attack of indole from the Re-face of β-CF3-β-disubstituted nitroalkene was favorable.
- Bao, Robert Li-Yuan,Fu, Kang,Shi, Lei
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- Photochemical C-H Activation Enables Nickel-Catalyzed Olefin Dicarbofunctionalization
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Alkenes, ethers, and alcohols account for a significant percentage of bulk reagents available to the chemistry community. The petrochemical, pharmaceutical, and agrochemical industries each consume gigagrams of these materials as fuels and solvents each year. However, the utilization of such materials as building blocks for the construction of complex small molecules is limited by the necessity of prefunctionalization to achieve chemoselective reactivity. Herein, we report the implementation of efficient, sustainable, diaryl ketone hydrogen-atom transfer (HAT) catalysis to activate native C-H bonds for multicomponent dicarbofunctionalization of alkenes. The ability to forge new carbon-carbon bonds between reagents typically viewed as commodity solvents provides a new, more atom-economic outlook for organic synthesis. Through detailed experimental and computational investigation, the critical effect of hydrogen bonding on the reactivity of this transformation was uncovered.
- Campbell, Mark W.,Yuan, Mingbin,Polites, Viktor C.,Gutierrez, Osvaldo,Molander, Gary A.
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p. 3901 - 3910
(2021/04/06)
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- Palladium-catalyzed fluoroacylation of (Hetero)arylboronic acid with fluorothioacetates at ambient temperature
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A palladium-catalyzed fluoroacylation of (hetero)aryl boronic acid with the fluorothioacetates is described at ambient temperature. A variety of aryl, and heteroaryl boronic acids are compatible in the reaction, affording the corresponding fluoroalkyl ketones in moderate to good yields. Further late-stage di-, and trifluoroacylation of drug molecule clofibrate and estrone demonstrated the synthetic practicability of this protocol.2009 Elsevier Ltd. All rights reserved.
- Ban, Shu-Rong,Cao, Ya-Fang,Dai, Hui-Xiong,Wang, Xing,Xu, Hui,Yi, Xing
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supporting information
(2020/03/23)
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- One-Pot Successive Turbo Grignard Reactions for the Facile Synthesis of α-Aryl-α-Trifluoromethyl Alcohols
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A novel straightforward one-pot methodology for two successive turbo Grignard reagent (iPrMgCl·LiCl) reactions, was developed for a facile synthesis of α-aryl-α-trifluoromethyl alcohols, motifs of value in pharmaceutical chemistry. The method displayed broad functional group tolerance, including reducible groups. Dual roles of iPrMgCl·LiCl were exploited in the tandem reaction with commercially available iodoarenes or iodoheteroarenes and 2,2,2-trifluoroethyl trifluoroacetate. The process encompasses three successive reactions in a one-pot process: the iPrMgCl·LiCl-mediated iodine/magnesium-exchange reaction of iodoarenes or iodoheteroarenes; nucleophilic addition of various generated aryl or heteroarylmagnesium reagents to 2,2,2-trifluoroethyl trifluoroacetate; and the reduction of in-situ generated aryl trifluoromethyl ketones with iPrMgCl·LiCl, to produce the corresponding α-aryl or α-heteroaryl-α-trifluoromethyl alcohols bearing various substituents, including reducible functional groups in good to excellent yields.
- Kani, Ryunosuke,Inuzuka, Toshiyasu,Kubota, Yasuhiro,Funabiki, Kazumasa
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supporting information
p. 4487 - 4493
(2020/06/01)
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- A Hammett Study of Clostridium acetobutylicum Alcohol Dehydrogenase (CaADH): An Enzyme with Remarkable Substrate Promiscuity and Utility for Organic Synthesis
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Described is a physical organic study of the reduction of three sets of carbonyl compounds by the NADPH-dependent enzyme Clostridium acetobutylicum alcohol dehydrogenase (CaADH). Previous studies in our group have shown this enzyme to display broad substrate promiscuity, yet remarkable stereochemical fidelity, in the reduction of carbonyl compounds, including α-, β- and γ-keto esters (d -stereochemistry), as well as α,α-difluorinated-β-keto phosphonate esters (l -stereochemistry). To better mechanistically characterize this promising dehydrogenase enzyme, we report here the results of a Hammett linear free-energy relationship (LFER) study across three distinct classes of carbonyl substrates; namely aryl aldehydes, aryl β-keto esters and aryl trifluoromethyl ketones. Rates are measured by monitoring the decrease in NADPH fluorescence at 460 nm with time across a range of substrate concentrations for each member of each carbonyl compound class. The resulting v 0 versus [S] data are subjected to least-squares hyperbolic fitting to the Michaelis-Menton equation. Hammett plots of log(V max) versus σ X yield the following Hammett parameters: (i) for p -substituted aldehydes, ρ = 0.99 ± 0.10, ρ = 0.40 ± 0.09; two domains observed, (ii) for p -substituted β-keto esters ρ = 1.02 ± 0.31, and (iii) for p -substituted aryl trifluoromethyl ketones ρ = -0.97 ± 0.12. The positive sign of ρ indicated for the first two compound classes suggests that the hydride transfer from the nicotinamide cofactor is at least partially rate-limiting, whereas the negative sign of ρ for the aryl trifluoromethyl ketone class suggests that dehydration of the ketone hydrate may be rate-limiting for this compound class. Consistent with this notion, examination of the 13 C NMR spectra for the set of p -substituted aryl trifluo romethyl ketones in 2percent aqueous DMSO reveals significant formation of the hydrate (gem -diol) for this compound family, with compounds bearing the more electron-withdrawing groups showing greater degrees of hydration. This work also presents the first examples of the CaADH-mediated reduction of aryl trifluoromethyl ketones, and chiral HPLC analysis indicates that the parent compound α,α,α-trifluoroacetophenone is enzymatically reduced in 99percent ee and 95percent yield, providing the (S)-stereoisomer, suggesting yet another compound class for which this enzyme displays high enantioselectivity.
- Berkowitz, David B.,Kudalkar, Gaurav P.,Lee, Joshua D.,Tiwari, Virendra K.
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p. 237 - 247
(2020/02/18)
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- CONDENSED IMIDAZOLE DERIVATIVES SUBSTITUTED BY TERTIARY HYDROXY GROUPS AS PI3K-GAMMA INHIBITORS
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This application relates to compounds of Formula (I): or pharmaceutically acceptable salts thereof, which are inhibitors of PI3K-y which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.
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Page/Page column 273-274
(2019/05/10)
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- Visible light-promoted umpolung coupling of aryl tri-/difluoroethanones with 2-alkenylpyridines
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Tertiary alcohols bearing a trifluoromethyl group are of considerable medicinal interest. Using an umpolung strategy, we herein report the first intermolecular reductive cross-coupling of aryl tri-/difluoroethanones with 2-alkenylpyridines with the aid of a Br?nsted acid catalyst upon visible-light irradiation. This metal-free reaction is operationally simple and performed at ambient temperature, allowing access to desired tertiary alcohols with tri-/difluoromethyl groups in moderate to excellent yields. The commercially available and easily handled Hantzsch ester effectively serves as an electron donor, as well as a hydrogen atom source.
- Xu, Xiao,Min, Qing-Qiang,Li, Na,Liu, Feng
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p. 11017 - 11020
(2018/10/08)
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- Catalytic Geminal Difluorination of Styrenes for the Construction of Fluorine-rich Bioisosteres
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A geminal difluorination of alkenes based on I(I)/I(III) catalysis is disclosed, which is compatible with a range of electronically and substitutionally diverse styrenes (27 examples, up to 89% yield). Employing inexpensive p-TolI as the organocatalyst, turnover is enabled by Selectfluor-mediated oxidation to generate the ArIF2 species in situ. Extension to include α-substituted styrenes bearing fluorine-containing groups is disclosed and provides an expansive platform for the generation of fluorine-rich architectures.
- Scheidt, Felix,Neufeld, Jessica,Sch?fer, Michael,Thiehoff, Christian,Gilmour, Ryan
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supporting information
p. 8073 - 8076
(2019/01/04)
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- MgCl2-catalyzed trifluoromethylation of carbonyl compounds using (trifluoromethyl)trimethylsilane as the trifluoromethylating agent
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Using (trifluoromethyl)trimethylsilane (TMSCF3) as the trifluoromethylating agent, MgCl2-catalyzed trifluoromethylation of carbonyl compounds proceeded readily at room temperature. In the presence of 10 mol% of MgCl2, a variety of carbonyl substrates such as aliphatic/aromatic aldehydes, acyclic/cyclic ketones and esters could be trifluoromethylated in DMF, giving the corresponding trimethylsilyl ethers (ketals) in up to 93% isolated yields. Trifluoromethylketones could be readily obtained after hydrolysis of the trimethylsilyl ketals. The reactions could tolerate air and moisture, and the use of oxygen and moisture-free conditions was not required.
- Cui, Bin,Sun, Hui,Xu, Yibo,Duan, Lili,Li, Yue-Ming
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p. 6754 - 6762
(2017/11/09)
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- Copper-Mediated Trifluoroacetylation of Arenediazonium Salts with Ethyl Trifluoropyruvate
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A copper-mediated trifluoroacetylation of various arenediazonium salts with ethyl trifluoropyruvate is reported. The reaction proceeded smoothly under mild conditions at room temperature giving trifluoromethyl aryl ketones in moderate to good yields. A variety of functional groups, including methoxy, hydroxy, ester, ketone, trifluoromethyl, and halide groups, were well tolerated. A possible reaction mechanism involving an aryl radical intermediate was proposed and supported by experimental evidence. This reaction provides a new route to trifluoromethyl aryl ketones, notable synthetic targets, from the corresponding anilines.
- Wu, Wei,Tian, Qinli,Chen, Taotao,Weng, Zhiqiang
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supporting information
p. 16455 - 16458
(2016/11/11)
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- Asymmetric Construction of Pyrrolidines Bearing a Trifluoromethylated Quaternary Stereogenic Center via CuI-Catalyzed 1,3-Dipolar Cycloaddition of Azomethine Ylides with β-CF3-β,β-Disubstituted Nitroalkenes
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A direct and convenient method has been developed for the synthesis of optically active pyrrolidines bearing a quaternary stereogenic center containing a CF3 group at the C-3 position of the pyrrolidine ring. The synthesis system, CuI/Si-FOXAP-catalyzed exo-selective 1,3-dipolar cycloaddition of azomethine ylides with β-CF3-β,β-disubstituted nitroalkenes, provides pyrrolidines with high diastereoselectivities (up to >98:2 d.r.) and excellent enantioselectivities (up to >99.9 ee) and performs well for a broad scope of substrates under mild conditions.
- Tang, Li-Wei,Zhao, Bao-Jing,Dai, Li,Zhang, Man,Zhou, Zhi-Ming
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p. 2470 - 2477
(2016/09/13)
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- Synthesis of Perfluoroalkyl-Substituted Vinylcyclopropanes by Way of Enhanced Neighboring Group Participation
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A simple, high yielding, two-step, one-pot protocol for the preparation of trifluoromethyl-substituted vinylcyclopropanes from α-CF3 homoallyl alcohols is disclosed. Destabilization of the cationic intermediate by the electron-withdrawing CF3 group greatly enhances neighboring group participation of the alkene, allowing ring closure to predominate. The reaction can be extended to the difluoromethyl and pentafluoroethyl group, enabling the preparation of a diverse array of fluoroalkyl-substituted vinylcyclopropanes. A diverse array of fluoroalkyl-substituted vinylcyclopropanes are prepared in a simple, high-yielding, two-step, one-pot protocol by means of cationic ring-closure.
- Kelly, Christopher B.,Mercadante, Michael A.,Carnaghan, Emma R.,Doherty, Matthew J.,Fager, Diana C.,Hauck, John J.,Macinnis, Allyson E.,Tilley, Leon J.,Leadbeater, Nicholas E.
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p. 4071 - 4076
(2015/06/30)
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- Organocatalytic Aerobic Oxidation of α-Fluoroalkyl Alcohols to Fluoroalkyl Ketones at Room Temperature
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The organocatalytic aerobic oxidation of electron-deficient α-fluoroalkyl alcohols at room temperature is described. The resulting fluoroalkyl ketones are versatile synthetic intermediates for a variety of fluorine-containing molecules. This otherwise difficult transformation has now been accomplished by the reaction of α-fluoroalkyl alcohols with N-oxyl radicals, catalytically generated from 9-azabicyclo[3.3.1]nonan-3-one N-oxyl/nitrogen oxide (keto-ABNO/NOx) and oxygen in acetic acid (AcOH), affording the corresponding fluoroalkyl ketones in high yield. This operationally simple reaction can be performed under mild conditions, and was applied to a wide range of alcohols (20 examples), thus demonstrating a high functional group tolerance. Moreover, a modified one-pot protocol based on this method was able to convert an aldehyde to a trifluoromethyl ketone on a gram scale.
- Kadoh, Yoichi,Tashiro, Masayuki,Oisaki, Kounosuke,Kanai, Motomu
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p. 2193 - 2198
(2015/07/27)
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- Palladium-Catalyzed Trimethylenemethane Cycloaddition of Olefins Activated by the δ-Electron-Withdrawing Trifluoromethyl Group
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α-Trifluoromethyl-styrenes, trifluoromethyl-enynes, and dienes undergo palladium-catalyzed trimethylenemethane cycloadditions under mild reaction conditions. The trifluoromethyl group serves as a unique δ-electron-withdrawing group for the activation of the olefin toward the cycloaddition. This method allows for the formation of exomethylene cyclopentanes bearing a quaternary center substituted by the trifluoromethyl group, compounds of interest for the pharmaceutical, agrochemical, and materials industries. In the diene series, the cycloaddition operates in a [3 + 4] and/or [3 + 2] manner to give rise to seven- and/or five-membered rings. This transformation greatly improves the scope of the TMM cycloaddition technology and provides invaluable insights into the reaction mechanism.
- Trost, Barry M.,Debien, Laurent
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p. 11606 - 11609
(2015/09/28)
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- One-pot multistep synthesis of trisubstituted alkenes from N -tosylhydrazones and alcohols
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A one-pot procedure for the synthesis of trisubstituted alkenes from N-tosylhydrazones and alcohols is reported. This procedure combines the aerobic oxidation reaction and Wittig reaction in one pot, which avoids using of environmentally toxic oxidants and isolation of the intermediates. The simple procedure makes it very attractive for the synthesis of trisubstituted alkenes when alcohols are used as starting materials. A variety of trisubstituted alkenes as well as trifluoromethyl-substituted alkenes were obtained in moderate to good yields (up to 84%) with good E-selectivity (up to 99%). Georg Thieme Verlag Stuttgart.New York.
- Sha, Qiang,Wei, Yunyang
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supporting information
p. 2353 - 2361
(2014/11/08)
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- Catalytic asymmetric hydrogenation of α-CF3- or β-CF3-Substituted acrylic acids using Rhodium(I) complexes with a combination of chiral and achiral ligands
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Only the mixture works! Acrylic acid derivatives with CF3 substituents in α or β position were efficiently hydrogenated in the presence of a RhI complex with a chiral secondary phosphine oxide (SPO; see scheme) and an achiral Ph3P as ligands. The corresponding propanoic acid derivatives were obtained with generally high conversion (>99 %) and high enantioselectivity (92->99 %). Copyright
- Dong, Kaiwu,Li, Yang,Wang, Zheng,Ding, Kuiling
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supporting information
p. 14191 - 14195
(2014/01/06)
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- Highly efficient synthesis of aryl and heteroaryl trifluoromethyl ketones via o-iodobenzoic acid (IBX)
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A two-step process for the synthesis of aryl and heteroaryl trifluoromethyl ketones from the corresponding aldehydes is described. Trifluoromethyl alcohols were prepared from aryl and heteroaryl aldehydes in excellent yields using catalytic amount of K2CO3. The trifluoromethyl alcohols were then oxidized conveniently and efficiently by o-iodoxybenzoic acid (IBX) under mild conditions to get the desired functionalized aryl and heteroaryl trifluoromethyl ketones.
- Cheng, Huicheng,Pei, Yu,Leng, Faqiang,Li, Jingya,Liang, Apeng,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
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p. 4483 - 4486
(2013/07/26)
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- A coupling of benzamides and donor/acceptor diazo compounds to form γ-lactams via Rh(III)-catalyzed C-H activation
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The coupling of O-pivaloyl benzhydroxamic acids with donor/acceptor diazo compounds provides isoindolones in high yield. The reaction tolerates a broad range of benzhydroxamic acids and diazo compounds, including substituted 2,2,2-trifluorodiazoethanes. Mechanistic experiments suggested that C-H activation is turnover-limiting and irreversible and that insertion of the diazo compound favors electron-deficient substrates.
- Hyster, Todd K.,Ruhl, Kyle E.,Rovis, Tomislav
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supporting information
p. 5364 - 5367
(2013/05/22)
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- Synthesis of a potent photoreactive acidic γ-secretase modulator for target identification in cells
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Supramolecular self-assembly of amyloidogenic peptides is closely associated with numerous pathological conditions. For instance, Alzheimers disease (AD) is characterized by abundant amyloid plaques originating from the proteolytic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Compounds named γ-secretase modulators (GSMs) can shift the substrate cleavage specificity of γ-secretase toward the production of non-amyloidogenic, shorter Aβ fragments. Herein, we describe the synthesis of highly potent acidic GSMs, equipped with a photoreactive diazirine moiety for photoaffinity labeling. The probes labeled the N-terminal fragment of presenilin (the catalytic subunit of γ-secretase), supporting a mode of action involving binding to γ-secretase. This fundamental step toward the elucidation of the molecular mechanism governing the GSM-induced shift in γ-secretase proteolytic specificity should pave the way for the development of improved drugs against AD.
- Rennhack, Andreas,Bulic, Bruno,Jumpertz, Thorsten,Ness, Julia,Baches, Sandra,Weggen, Sascha,Pietrzik, Claus U.
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p. 6523 - 6532,10
(2012/12/12)
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- Synthesis of a potent photoreactive acidic γ-secretase modulator for target identification in cells
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Supramolecular self-assembly of amyloidogenic peptides is closely associated with numerous pathological conditions. For instance, Alzheime?s disease (AD) is characterized by abundant amyloid plaques originating from the proteolytic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Compounds named γ-secretase modulators (GSMs) can shift the substrate cleavage specificity of γ-secretase toward the production of non-amyloidogenic, shorter Aβ fragments. Herein, we describe the synthesis of highly potent acidic GSMs, equipped with a photoreactive diazirine moiety for photoaffinity labeling. The probes labeled the N-terminal fragment of presenilin (the catalytic subunit of γ-secretase), supporting a mode of action involving binding to γ-secretase. This fundamental step toward the elucidation of the molecular mechanism governing the GSM-induced shift in γ-secretase proteolytic specificity should pave the way for the development of improved drugs against AD.
- Rennhack, Andreas,Jumpertz, Thorsten,Ness, Julia,Baches, Sandra,Pietrzik, Claus U.,Weggen, Sascha,Bulic, Bruno
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p. 6523 - 6532
(2013/01/14)
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- Silver compounds in synthetic chemistry. Part 5: Selective syntheses of trifluoromethylketones, RCOCF3, from trifluoromethylsilver, AgCF3, and corresponding acyl chlorides, RCOCl
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Trifluoromethylketones of aromatics, heteroaromatics and olefins are formed selectively from reactions of trifluoromethylsilver and the corresponding carboxylic acid chlorides in moderate to excellent yields. The conditions chosen are dependent on the nature of the acyl chloride. Attempts to prepare alkyl(trifluoromethyl)ketones yielded product mixtures of the corresponding acyl fluorides, trifluoromethyl-, pentafluoroethyl- and n-heptafluoropropyl ketones.
- Kremlev, Mikhail M.,Mushta, Aleksej I.,Tyrra, Wieland,Naumann, Dieter,Fischer, Hendrik T.M.,Yagupolskii, Yurii L.
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p. 1385 - 1389
(2008/09/18)
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- Convenient synthesis of a [1-14C]diazirinylbenzoic acid as a photoaffinity label for binding studies of V-ATPase inhibitors
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Diazirine-tagged systems are considered reliable compounds for photoaffinity labeling (PAL) in biochemical studies as they enable investigation and understanding of biological mechanisms through covalent bonding to the target and subsequent detection. 14C-labeled 4-(3-trifluoromethyl-3H- diazirin-3-yl)benzoic acid (11) was prepared by a lithium-bromide exchange on the bis-silylated 4-bromophenyldiaziridine 19 with subsequent transformations with electrophiles as key steps of the synthesis. Using 14CO 2, which was generated from rather inexpensive Ba14CO 3, the desired diaziridinylbenzoic acid 21 was obtained in 78% yield based on the employed radioactive material. Oxidation under mild conditions then yielded diazirine 11 in a 100 mg scale. This versatile photoaffinity label was selectively attached to the tetrahydropyrane ring of bafilomycin A1 (2) and concanamycin A-derived 3, which both specifically inhibit the V-ATPases. Inhibition assays were performed and revealed that the inhibitory capacities of the labeled derivatives are suitable for PAL studies on this important group of enzymes to elucidate the as yet unknown binding sites. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Bender, Tobias,Huss, Markus,Wieczorek, Helmut,Grond, Stephanie,Von Zezschwitz, Paultheo
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p. 3870 - 3878
(2008/02/13)
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- N-Isoxazolyl-biphenylsulfonamide derivatives, their preparation and their use as endothelin antagonists
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A compound of the formula I an enantiomer, diastereomer or pharmaceutically acceptable salt thereof, wherein: one of X and Y is N and the other is O; R2,R3,R4 and R5 are each independently (a) hydrogen;(b) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted with Z1, Z2 and Z3;(c) halo;(d) hydroxyl;(e) cyano;(f) nitro;(g)-C(O)H or-C(O)R6;(h)-CO2H or-CO2R6;(i)-SH,-S(O)nR6 ,-S(O)m-OH,-S(O)m-OR6,-O-S(O)m-R6,-O-S(O)mOH or-O-S(O)m-OR6;(j)-Z4-NR7R8; or(k)-Z4-N(R11)-Z5-NR9 R10; R4 and R5 together are alkylene or alkenylene, either of which may be substituted with Z1,Z2 and Z3, completing a 4-to 8-membered saturated, unsaturated or aromatic ring together with the carbon atoms to which they are attached; G1 is (a) hydrogen; or(b) alkyl; G2 is (a) hydroxyalkyl;(b)-(CH2)mOR6; or(c)-(CH2)m-NR12 R13;(d) mono-to hexa-halo substituted alkyl; or(e)-(CH2)n OR14; and the remaining symbols are as defined in the description.The compounds of formula I are antagonists of ET-1, ET-2 and /or ET-3 and are useful in treatment of conditions associated with increased ET levels (e.g., dialysis, trauma and surgery) and of all endothelin-dependent disorders. They are thus inter alia useful as antihypertensive agents.
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- Process for preparing trifluoromethyl ketones
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A process is described for preparing trifluoromethyl ketones of the formula I STR1 where R has the given meanings, wherein an alcohol of the formula II STR2 is reacted with a compound of the formula IV where n has the given meaning.
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- Insecticidal ethers
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This invention relates to novel fluorinated ethers, useful as insecticides and acaricides, to processes and intermediates for their preparation, to insecticidal and acaricidal compositions thereof and to methods of combating and controlling insect and acarine pests therewith.
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- Process for intermediates for insecticidal compounds
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The invention provides novel arylalkene compounds of formula I, a process for their preparation and their use as intermediates for insecticidal compounds, comprising, STR1 wherein W represents 1 to 4 substituents selected from halo, alkyl, alkoxy, haloalkyl, haloalkoxy and alkoxyalkyl, or W represents a bidentate alkylene or alkylenedioxy group linking adjacent carbon atoms, X represents fluoroalkyl, and Y is selected from chlorine, bromine and alkoxy; and a process for preparing said ethers. The compounds of formula I are prepared by reacting a ketone of formula: STR2 with a phosphonium salt of formula Hal - (Q) 3 P + -CH 2 -Y, where Hal - represents a halide ion and Q represents alkyl or aryl.
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- Diphenyl ether derivatives and their use as insecticides
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A compound of formula: STR1 wherein W represents one or more substituents selected from halo, alkyl, alkoxy, alkoxyalkyl, haloalkyl and haloalkoxy or W represents a bidentate group linking adjacent carbon atoms selected from alkylene and alkylenedioxy; Y is a group of formula STR2 wherein X is a group of formula --(CF2)n R3, where R3 is selected from hydrogen, chloro and fluoro, and n is one or two, R1 is selected from hydrogen, chloro, fluoro and hydroxy and R2 is selected from methyl, cyano, ethynyl and hydrogen; Q is selected from carbon bearing a hydrogen atom and nitrogen; and Z represents one or more substituents selected from fluoro, benzyl, phenoxy, chlorophenoxy, fluorophenoxy and bromophenoxy, or any isomer thereof. Processes for preparing these compounds and intermediates for use therein, insecticidal compositions containing these compounds and the use thereof are also disclosed.
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