- Copper-Catalyzed Asymmetric Radical 1,2-Carboalkynylation of Alkenes with Alkyl Halides and Terminal Alkynes
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A copper-catalyzed intermolecular three-component asymmetric radical 1,2-carboalkynylation of alkenes has been developed, providing straightforward access to diverse chiral alkynes from readily available alkyl halides and terminal alkynes. The utilization of a cinchona alkaloid-derived multidentate N,N,P-ligand is crucial for the efficient radical generation from mildly oxidative precursors by copper and the effective inhibition of the undesired Glaser coupling side reaction. The substrate scope is broad, covering (hetero)aryl-, alkynyl-, and aminocarbonyl-substituted alkenes, (hetero)aryl and alkyl as well as silyl alkynes, and tertiary to primary alkyl radical precursors with excellent functional group compatibility. Facile transformations of the obtained chiral alkynes have also been demonstrated, highlighting the excellent complementarity of this protocol to direct 1,2-dicarbofunctionalization reactions with C(sp2/sp3)-based reagents.
- Dong, Xiao-Yang,Cheng, Jiang-Tao,Zhang, Yu-Feng,Li, Zhong-Liang,Zhan, Tian-Ya,Chen, Ji-Jun,Wang, Fu-Li,Yang, Ning-Yuan,Ye, Liu,Gu, Qiang-Shuai,Liu, Xin-Yuan
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Read Online
- First Total Synthesis of Niphatesines A-D and Assignment of Absolute Configuration
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Regio/Enantioselective synthesis of niphatesines A-D is achieved making use of Pd(0) assisted 3-alkylation of pyridine as the key step.Absolute configuration of niphatesines C and D is established.
- Rao, A. V. Rama,Reddy, Gongiti Ravindra
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Read Online
- 3-Ethenylpyridine Measured in Urine of Active and Passive Smokers: A Promising Biomarker and Toxicological Implications
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In studies of tobacco toxicology, including comparisons of different tobacco products and exposure to secondhand or thirdhand smoke, exposure assessment using biomarkers is often useful. Some studies have indicated that most of the toxicity of tobacco smoke is due to gas-phase compounds. 3-Ethenylpyridine (3-EP) is a major nicotine pyrolysis product occurring in the gas phase of tobacco smoke. It has been used extensively as an environmental tracer for tobacco smoke. 3-EP would be expected to be a useful tobacco smoke biomarker as well, but nothing has been published about its metabolism and excretion in humans. In this Article we describe a solid-phase microextraction (SPME) GC-MS/MS method for determination of 3-EP in human urine and its application to the determination of 3-EP in the urine of smokers and people exposed to secondhand smoke. We conclude that 3-EP is a promising biomarker that could be useful in studies of tobacco smoke exposure and toxicology. We also point out the paucity of data on 3-EP toxicity and suggest that additional studies are needed.
- Liu, Jia,Benowitz, Neal L.,Hatsukami, Dorothy K.,Havel, Christopher M.,Lazcano-Ponce, Eduardo,Strasser, Andrew A.,Jacob, Peyton
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Read Online
- Interconversion of nicotine enantiomers during heating and implications for smoke from combustible cigarettes, heated tobacco products, and electronic cigarettes
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Physiological properties of (R)-nicotine have differences compared with (S)-nicotine, and the subject of (S)- and (R)-nicotine ratio in smoking or vaping related items is of considerable interest. A Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) method for the analysis of (S)- and (R)-nicotine has been developed and applied to samples of nicotine from different sources, nicotine pyrolyzates, several types of tobacco, smoke from combustible cigarettes, smoke from heated tobacco products, e-liquids, and particulate matter obtained from e-cigarettes aerosol. The separation was achieved on a Chiracel OJ-3 column, 250 × 4.6 mm with 3-μm particles using a nonaqueous mobile phase. The detection was performed using atmospheric pressure chemical ionization (APCI) in positive mode. The only transition measured for the analysis of nicotine was 163.1 → 84.0. The method has been summarily validated. For the analysis, the samples of tobacco and smoke from combustible cigarettes were subject to a cleanup procedure using solid phase extraction (SPE). It was demonstrated that nicotine upon heating above 450°C for several minutes starts decomposing, and some formation of (R)-enantiomer from a sample of 99% (S)-nicotine is observed. An analogous process takes place when a 99% (R)-nicotine is heated and forms low levels of (S)-nicotine. This interconversion has the effect of slightly increasing the content of (R)-nicotine in smoke compared with the level in tobacco for combustible cigarettes and for heated tobacco products. The (S)/(R) ratio of nicotine enantiomers in e-liquids was identical with the ratio for the particulate phase of aerosols generated by e-cigarette vaping.
- Moldoveanu, Serban C.
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p. 667 - 677
(2022/02/02)
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- COMPOSITIONS AND METHODS FOR PARASITE CONTROL
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The present invention relates in its broadest aspect to a compound of Formula I as provided herein, formulations comprising such a compound and corresponding uses thereof for the reduction of infestation with ectoparasites, in particular ectoparasites of the insect class, including fleas and mosquitoes and/or ectoparasites of the arachnid class, including ticks and mites, etc. Also provided herein are methods for preparing the formulations of the invention and methods for controlling ectoparasites using the compounds and/or formulations provided herein.
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Page/Page column 55; 93; 100
(2022/01/05)
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- Creation of Redox-Active PdSx Nanoparticles Inside the Defect Pores of MOF UiO-66 with Unique Semihydrogenation Catalytic Properties
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Semihydrogenation of alkynes to produce alkenes is very important in the industry; however, over-hydrogenation heavily complicates the postprocesses, which are highly energy consuming and not environmentally friendly. One of the most efficient pathways to solve this challenging issue is to develop highly selective catalysts that could only hydrogenate alkynes and are inactive in hydrogenation of alkenes. This work presents herein an efficient catalyst, consisting of in situ created PdS0.53 nanoparticles as the redox-active sites inside the defect pores of metal–organic framework UiO-66, which demonstrates very high alkene selectivity (up to 99.5%) in semihydrogenation of easily over-hydrogenated terminal alkynes. In contrast to the traditional catalysts, strict control over the reaction time becomes the nonessential condition because the catalyst system is almost inactive in hydrogenation of alkenes. Therefore, this paradigm work provides a practically applicable pathway for the development of efficient catalysts with unique catalytic properties for selective semihydrogenation reactions.
- Dong, Ming-Jie,Wang, Xuan,Wu, Chuan-De
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- An Annelated Mesoionic Carbene (MIC) Based Ru(II) Catalyst for Chemo- And Stereoselective Semihydrogenation of Internal and Terminal Alkynes
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The catalytic utility of [RuL1(CO)2I2] (1), containing an annelated π-conjugated imidazo-naphthyridine-based mesoionic carbene (MIC) ligand (L1), is evaluated for E-selective alkyne semihydrogenation. The precatalyst 1, in combination with 2 equiv of AgBArF, semihydrogenates a broad range of internal alkynes with molecular hydrogen (5 bar) in water. (E)-Alkenes are accessed in high yields, and a number of reducible functional groups are tolerated. A chelate MIC ligand and two cis carbonyls provide a well-defined platform at the Ru center for hydrogenation and isomerization. The loss of two iodides and the presence of two carbonyls render the Ru center electron deficient and thus the formation of metal vinylidenes with terminal alkynes is avoided. This is leveraged for the semihydrogenation of terminal alkynes by the same catalytic system in isopropyl alcohol. Reaction profile, isomerization, kinetic, and DFT studies reveal initial alkyne hydrogenation to a (Z)-alkene, which further isomerizes to an (E)-alkene via metal-catalyzed Z → E isomerization.
- Bera, Jitendra K.,Choudhury, Joyanta,Das, Shubhajit,Dutta, Indranil,Pati, Swapan K.,Saha, Sayantani,Yadav, Suman
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p. 3212 - 3223
(2020/10/02)
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- Iron-Catalyzed Direct Julia-Type Olefination of Alcohols
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Herein, we report an iron-catalyzed, convenient, and expedient strategy for the synthesis of styrene and naphthalene derivatives with the liberation of dihydrogen. The use of a catalyst derived from an earth-abundant metal provides a sustainable strategy to olefins. This method exhibits wide substrate scope (primary and secondary alcohols) functional group tolerance (amino, nitro, halo, alkoxy, thiomethoxy, and S- A nd N-heterocyclic compounds) that can be scaled up. The unprecedented synthesis of 1-methyl naphthalenes proceeds via tandem methenylation/double dehydrogenation. Mechanistic study shows that the cleavage of the C-H bond of alcohol is the rate-determining step.
- Landge, Vinod G.,Babu, Reshma,Yadav, Vinita,Subaramanian, Murugan,Gupta, Virendrakumar,Balaraman, Ekambaram
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p. 9876 - 9886
(2020/09/03)
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- INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN
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Compounds and compositions for modulating fibroblast activation protein (FAP) are described. The compounds and compositions may find use as therapeutic agents for the treatment of diseases, including hyperproliferative diseases.
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Paragraph 0195
(2020/07/14)
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- Synthetic Entry to Polyfunctionalized Molecules through the [3+2]-Cycloaddition of Thiocarbonyl Ylides
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Here we present a comprehensive study on the [3+2]-cycloaddition of thiocarbonyl ylides with a wide variety of alkenes and alkynes. The obtained dihydro- and tetrahydrothiophene products serve as exceptionally versatile intermediates providing access to thiophenes, dienes, dendralenes, and vic-quarternary carbon centers. The use of high-pressure conditions enables thermally unstable, sterically encumbered or moderately reactive substrates to undergo the cycloaddition under mild conditions, thereby increasing the yield by up to 58percent. In addition, we showcase its utility by the formal syntheses of the pharmaceuticals NGB 4420 and tenilapine.
- Habiger, Christoph,Haut, Franz-Lucas,Korber, Johannes Nepomuk,Müller, Thomas,Magauer, Thomas,Mayer, Peter,Speck, Klaus,Wurst, Klaus
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supporting information
(2019/09/06)
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- Method for selective synthesis of cis-olefins and trans-olefins by semi-reduction of alcohol hydrogen supply palladium-catalyzed alkynes
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The invention provides a method for selective synthesis of cis-olefins and trans-olefins by semi-reduction of alcohol hydrogen supply palladium-catalyzed alkynes. The method comprises the following steps: performing alkyne reduction reaction with TEOA, NaOAc, a catalyst, alcohol and alkynes in an organic solvent and generating the cis-olefins after reaction; performing alkyne reduction reaction with a ligand, a catalyst, alcohol and alkynes in an organic solvent and generating the trans-olefins after reaction; a reactor for the reduction reaction is a sealed pressure-resistant reactor, the reduction reaction temperature is 120-150 DEG C, and the reduction reaction time is 20-48 hours; the dosage of the catalyst is 5-20 percent of the molar dosage of the alkynes, and the dosage of the alcohol is 10-100 times of the molar dosage of the alkynes; the dosage of R, R-DIPAMP is 0.5-5 times of the molar dosage of the alkynes. According to the method provided by the invention, a catalyst systemhas extremely-high chemical reaction and stereo-selectivity and can synthesize cis-olefin products or trans-olefin products with high yield; the catalyst system is good universality to a substrate, and the alkynes containing various functional groups can be efficiently subjected to the highly-selective reduction reactions.
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Paragraph 0207-0209
(2019/06/07)
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- Monodisperse nickel-nanoparticles for stereo- and chemoselective hydrogenation of alkynes to alkenes
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Here, we report the use of monosaccharides for the preparation of novel nickel nanoparticles (NP), which constitute selective hydrogenation catalysts. For example, immobilization of fructose and Ni(OAc)2 on silica and subsequent pyrolysis under inert atmosphere produced graphitic shells encapsulated Ni-NP with uniform size and distribution. Interestingly, fructose acts as structure controlling compound to generate specific graphitic layers and the formation of monodisperse NP. The resulting stable and reusable catalysts allow for stereo- and chemoselective semihydrogenation of functionalized and structurally diverse alkynes in high yields and selectivity.
- Murugesan, Kathiravan,Alshammari, Ahmad S.,Sohail, Manzar,Beller, Matthias,Jagadeesh, Rajenahally V.
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p. 372 - 377
(2019/01/26)
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- Design and characterization of a heterocyclic electrophilic fragment library for the discovery of cysteine-targeted covalent inhibitors
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A fragment library of electrophilic small heterocycles was characterized through cysteine-reactivity and aqueous stability tests that suggested their potential as covalent warheads. The analysis of theoretical and experimental descriptors revealed correlations between the electronic properties of the heterocyclic cores and their reactivity against GSH that are helpful in identifying suitable fragments for cysteines with specific nucleophilicity. The most important advantage of these fragments is that they show only minimal structural differences from non-electrophilic counterparts. Therefore, they could be used effectively in the design of targeted covalent inhibitors with minimal influence on key non-covalent interactions.
- Keeley,ábrányi-Balogh,Keseru
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supporting information
p. 263 - 267
(2019/03/05)
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- Method for synthesizing olefin compound by photo-induced one-pot process
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The invention discloses a method for synthesizing an olefin compound by a photo-induced one-pot process. The method comprises the following step of subjecting a halohydrocarbon and an aldehyde compound to a reaction under the condition of irradiation in an inert atmosphere by taking alkali metal carbonate as a base, taking an organic phosphine compound as an adjuvant and taking a photosensitizer as a catalyst, thereby obtaining the olefin compound. According to the method disclosed by the invention, the olefin compound is produced from the halohydrocarbon and the aldehyde compound in a high-yield manner under the condition of irradiation in the inert atmosphere under normal-temperature reaction conditions by taking acetonitrile, DMF (N,N-dimethylformamide) or DMA (N,N-dimethylacetamide) asa solvent, taking an organic phosphine reagent as a reaction adjuvant, taking the alkali metal carbonate as the base and taking the photosensitizer as the catalyst. Compared with the conventional olefin synthesis methods, the method disclosed by the invention has the obvious advantages that the reaction raw materials are readily available, the tolerance to a variety of functional groups on halohydrocarbons and aldehydes is high, the yield is high, the separation and purification of a product are simple and convenient, and the like.
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Paragraph 0073-0075
(2018/11/03)
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- Model Guided Development of a Simple Catalytic Method for the Synthesis of Unsymmetrical Stilbenes by Sequential Heck Reactions of Aryl Bromides with Ethylene
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Stilbenes are important and useful structural moieties, but methods for their preparation typically possess numerous inefficiencies. Presented here is a methodology for the two-step, one pot preparation of unsymmetrical stilbenes via sequential Heck reactions. The first Heck reaction with ethylene gas was analysed as a function of temperature and pressure for electronically differentiated naphthyl bromides and model-aided reaction optimization was utilized to define the system. In addition, reactNMR was utilized to determine ethylene solubility in common organic solvents useful for Heck reactions. Finally, an optimized sequential Heck reaction process was developed and applied to a range of substrates allowing for efficient preparation of unsymmetrical stilbenes, including the natural antioxidant, pterostilbene. (Figure presented.).
- Barlow, Helen,Buser, Jonas Y.,Glauninger, Hendrik,Luciani, Carla V.,Martinelli, Joseph R.,Oram, Niall,Thompson-Van Hook, Nichole,Richardson, Jeffery
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p. 2678 - 2690
(2018/06/04)
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- Selective Semihydrogenation of Alkynes Catalyzed by Pd Nanoparticles Immobilized on Heteroatom-Doped Hierarchical Porous Carbon Derived from Bamboo Shoots
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Highly dispersed palladium nanoparticles (Pd NPs) immobilized on heteroatom-doped hierarchical porous carbon supports (N,O-carbon) with large specific surface areas are synthesized by a wet chemical reduction method. The N,O-carbon derived from naturally abundant bamboo shoots is fabricated by a tandem hydrothermal–carbonization process without assistance of any templates, chemical activation reagents, or exogenous N or O sources in a simple and ecofriendly manner. The prepared Pd/N,O-carbon catalyst shows extremely high activity and excellent chemoselectivity for semihydrogenation of a broad range of alkynes to versatile and valuable alkenes under ambient conditions. The catalyst can be readily recovered for successive reuse with negligible loss in activity and selectivity, and is also applicable for practical gram-scale reactions.
- Ji, Guijie,Duan, Yanan,Zhang, Shaochun,Fei, Benhua,Chen, Xiufang,Yang, Yong
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p. 3427 - 3434
(2017/09/15)
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- One-pot Suzuki-Heck relay to prepare industrially valuable intermediates using the Pd-Cy?Phine catalyst system
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A rare example of a one-pot, palladium-catalyzed Suzuki-Heck sequence has been developed with applicability to APIs and organoelectronic materials. High throughput screening was used to expedite development and survey strategies. Interchangeability of the coupling partners and the avoidance of intermediate isolation gives operational flexibility, which can be used to improve process efficiency and suppress by-product formation.
- Das, Uttam K.,Clément, Roxanne,Johannes, Charles W.,Robins, Edward G.,Jong, Howard,Baker, R. Tom
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p. 4599 - 4603
(2017/10/19)
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- A 2 - chloro - 5 - ethyl pyridine preparation method (by machine translation)
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The invention discloses a method for synthesizing 2 - chloro - 5 - ethyl pyridine method, by Suzuki reaction with 2 - chloro - 5 - bromo pyridine or by Wittig reaction with 2 - chloro - 5 - formyl pyridine is converted into 2 - chloro - 5 - vinyl pyridine; further uses the type (I) selective hydrogenation catalyst-containing structure, wherein R is cyclohexyl, butyl or phenyl, L is pyridine or unsaturated including nitrogen Cabeen, the 2 - chloro - 5 - vinyl pyridine is converted into 2 - chloro - 5 - ethyl pyridine. The method of the invention has a high selectivity, high yield and the advantage of convenient purification. (by machine translation)
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Paragraph 0019; 0037; 0038
(2017/08/25)
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- Visible Light-Induced Room-Temperature Heck Reaction of Functionalized Alkyl Halides with Vinyl Arenes/Heteroarenes
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The first visible light-induced Pd-catalyzed Heck reaction of α-heteroatom substituted alkyl iodides and -bromides with vinyl arenes/heteroarenes has been developed. This transformation efficiently proceeds at room temperature and enables synthesis of valuable functionalized allylic systems, such as allylic silanes, boronates, germanes, stannanes, pivalates, phosphonates, phthalimides, and tosylates from the corresponding α-substituted methyl iodides. Notably, synthesis of the latter substrates failed under existing thermally induced Pd-catalyzed conditions, which highlights the importance of visible light for this transformation.
- Kurandina, Daria,Parasram, Marvin,Gevorgyan, Vladimir
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supporting information
p. 14212 - 14216
(2017/10/13)
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- Direct Olefination of Alcohols with Sulfones by Using Heterogeneous Platinum Catalysts
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Carbon-supported Pt nanoparticles (Pt/C) were found to be effective heterogeneous catalysts for the direct Julia olefination of alcohols in the presence of sulfones and KOtBu under oxidant-free conditions. Primary alcohols, including aryl, aliphatic, allyl, and heterocyclic alcohols, underwent olefination with dimethyl sulfone and aryl alkyl sulfones to give terminal and internal olefins, respectively. Secondary alcohols underwent methylenation with dimethyl sulfone. Under 2.5 bar H2, the same reaction system was effective for the transformation of alcohol OH groups to alkyl groups. Structural and mechanistic studies of the terminal olefination system suggested that Pt0 sites on the Pt metal particles are responsible for the rate-limiting dehydrogenation of alcohols and that KOtBu may deprotonate the sulfone reagent. The Pt/C catalyst was reusable after the olefination, and this method showed a higher turnover number (TON) and a wider substrate scope than previously reported methods, which demonstrates the high catalytic efficiency of the present method. Olefination of alcohols: The first heterogeneous catalytic terminal and internal olefination of primary alcohols and methylenation of secondary alcohols with sulfones, a reusable carbon-supported Pt catalyst, and KOtBu is reported (see scheme).
- Hakim Siddiki,Touchy, Abeda Sultana,Kon, Kenichi,Shimizu, Ken-Ichi
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p. 6111 - 6119
(2016/04/26)
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- Iron-Catalyzed Cross-Coupling of Alkenyl Acetates
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Stable C-O linkages are generally unreactive in cross-coupling reactions which mostly employ more electrophilic halides or activated esters (triflates, tosylates). Acetates are cheap and easily accessible electrophiles but have not been used in cross-couplings because the strong C-O bond and high propensity to engage in unwanted acetylation and deprotonation. Reported herein is a selective iron-catalyzed cross-coupling of diverse alkenyl acetates, and it operates under mild reaction conditions (0 C, 2 h) with a ligand-free catalyst (1-2 mol%). Iron clad: Acetates are underutilized electrophiles in metal-catalyzed cross-coupling reactions because of the strong alkenyl C-O bond and their propensity to engage in unwanted reactions. Combination of a ligand-free low-valent Fe catalyst with nucleophilic organomagnesium reagents, low temperature, and short reaction times results in highly selective cross-couplings with alkenyl acetates.
- G?rtner, Dominik,Stein, André Luiz,Grupe, Sabine,Arp, Johannes,Von Wangelin, Axel Jacobi
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supporting information
p. 10545 - 10549
(2015/09/02)
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- Enantioselective Nickel-Catalyzed Hydrocyanation using Chiral Phosphine-Phosphite Ligands: Recent Improvements and Insights
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The asymmetric hydrocyanation of vinylarenes was investigated using hydrogen cyanide (HCN) in the presence of 5 mol% of a catalyst prepared from a phenol-derived chiral phosphine-phosphite ligand and bis(cyclooctadiene)nickel [Ni(cod)2]. The reactions were performed in tetrahydrofuran (THF) at room temperature to give exclusively the branched nitriles with superior enantioselectivities of 88-99% ee for vinylarenes and 74-94% ee for vinylheteroarenes, respectively. Using styrene as a model substrate it was shown that the catalyst loading could be decreased to 0.42 mol% without any loss of selectivity (88% ee). The structure of the pre-catalyst, i.e., a tetrahedral Ni(0)(P,P-chelate)(cod) complex, was proven by X-ray and NMR analysis. Additional insight into the reaction course was gained by monitoring the hydrocyanation of styrene-d8 by means of 2D NMR spectroscopy.
- Falk, Anna,Cavalieri, Alberto,Nichol, Gary S.,Vogt, Dieter,Schmalz, Hans-Günther
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supporting information
p. 3317 - 3320
(2015/11/03)
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- Mechanistic studies on the Pd-catalyzed vinylation of aryl halides with vinylalkoxysilanes in water: The effect of the solvent and NaOH promoter
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The mechanism of the Pd-catalyzed vinylation of aryl halides with vinylalkoxysilanes in water has been studied using different catalytic precursors. The NaOH promoter converts the initial vinylalkoxysilane into a highly reactive water-soluble vinylsilanolate species. Similarly, deuterium-labeling experiments have shown that, irrespective of the catalytic precursor used, vinylation occurs exclusively at the CH vinylic functionality via a Heck reaction and not at the C-Si bond via a Hiyama cross-coupling. The involvement of a Heck mechanism is interpreted in terms of the reduced nucleophilicity of the base in water, which disfavors the transmetalation step. The Heck product (β-silylvinylarene) undergoes partial desilylation, with formation of a vinylarene, by three different routes: (a) hydrolytic desilylation by the aqueous solvent (only at high temperature); (b) transmetalation of the silyl olefin on the PdH Heck intermediate followed by reductive elimination of vinylarene; (c) reinsertion of the silyl olefin into the PdH bond of the Heck intermediate followed by β-Si syn-elimination. Both the Hiyama and Heck catalytic cycles and desilylation mechanisms b and c have been computationally evaluated for the [Pd(en)Cl2] precursor in water as solvent. The calculated Gibbs energy barriers support the reinsertion route proposed on the basis of the experimental results.
- Gordillo, Alvaro,Ortuno, Manuel A.,Lopez-Mardomingo, Carmen,Lledos, Agusti,Ujaque, Gregori,De Jesus, Ernesto
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supporting information
p. 13749 - 13763
(2013/10/01)
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- Isoxazolines as Therapeutic Agents
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The present invention provides compound of Formula (I) biologically active metabolites, pro-drugs, isomers, stereoisomers, solvates, hydrates and pharmaceutically acceptable salts thereof wherein the variables are defined herein. The compounds of the invention are useful for treating immunological conditions.
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Paragraph 0909
(2013/03/26)
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- An easy access to styrenes: Trans aryl 1,3-, 1,4- and 1,5-dienes, and 1,3,5-trienes by Hiyama cross-coupling catalyzed by palladium nanoparticles
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A convenient and efficient procedure has been developed for the vinylation of aryl-, styrenyl-, cinnamyl- and dienyl-halides by a Pd(0) nanoparticle-catalyzed Hiyama cross-coupling to provide the corresponding dienes and trienes in high yields. The reaction does not require any ligand or co-catalyst, and is carried out using PdCl2 and tetrabutyl ammonium fluoride (TBAF) in THF. Pd nanoparticles are generated in situ and are the active catalytic species in this reaction. A wide range of functionalized styrenes, trans aryl 1,3-, 1,4- and 1,5- dienes, 1,2-, 1-3 and 1,4-bis(1,3-dienes), and 1,3,5-trienes can be obtained by this procedure. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011.
- Chatterjee, Tanmay,Dey, Raju,Ranu, Brindaban C.
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experimental part
p. 1103 - 1110
(2011/07/08)
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- Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl)ethenyl)indoles as potential anticancer immunomodulators
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Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance. IDO inhibition is thus an active area of research in drug development. Recently, our group has shown that tryptophan 2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzing the first step of tryptophan degradation, is also expressed in many tumors and that this expression prevents tumor rejection by locally depleting tryptophan. Herein, we report a structure-activity study on a series of 3-(2-(pyridyl)ethenyl)indoles. More than 70 novel derivatives were synthesized, and their TDO inhibitory potency was evaluated. The rationalization of the structure-activity relationships (SARs) revealed essential features to attain high TDO inhibition and notably a dense H-bond network mainly involving His55 and Thr254 residues. Our study led to the identification of a very promising compound (58) displaying good TDO inhibition (Ki = 5.5 μM), high selectivity, and good oral bioavailability. Indeed, 58 was chosen for preclinical evaluation.
- Dolu?i?, Eduard,Larrieu, Pierre,Moineaux, Laurence,Stroobant, Vincent,Pilotte, Luc,Colau, Didier,Pochet, Lionel,Van Den Eynde, Beno?t,Masereel, Bernard,Wouters, Johan,Frédérick, Rapha?l
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supporting information; scheme or table
p. 5320 - 5334
(2011/10/02)
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- Total synthesis of haminol A: An analysis of vinylpyridine metathesis reactivity
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The total synthesis of haminol A has been completed featuring a masked-alkene metathesis reaction followed by bis-acyloxysulfone elimination to install the 1,3,8-triene subunit. During the course of our synthesis, the metathesis reactivity of 3-vinylpyridine was evaluated and our data suggest the rapid formation of a ruthenium pyridylalkylidene that no longer participates in productive metathesis. A chemotaxis assay using Caenorhabditis elegans demonstrated that haminol A produced an avoidance response from this organism.
- Storvick, Jennifer M.,Ankoudinova, Evgenia,King, Brianne R.,Van Epps, Heather,O'Neil, Gregory W.
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supporting information; experimental part
p. 5858 - 5861
(2011/12/14)
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- α-Selective Ni-catalyzed hydroalumination of aryl- and alkyl-substituted terminal alkynes: Practical syntheses of internal vinyl aluminums, halides, or boronates
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A method for Ni-catalyzed hydroalumination of terminal alkynes, leading to the formation of α-vinylaluminum isomers efficiently (>98% conv in 2-12 h) and with high selectivity (95% to >98% α), is described. Catalytic α-selective hydroalumination reactions proceed in the presence of a reagent (diisobutylaluminum hydride; dibal-H) and 3.0 mol % metal complex (Ni(dppp)Cl2) that are commercially available and inexpensive. Under the same conditions, but with Ni(PPh3)2Cl2, hydroalumination becomes highly β-selective, and, unlike uncatalyzed transformations with dibal-H, generates little or no alkynylaluminum byproducts. All hydrometalation reactions are reliable, operationally simple, and practical and afford an assortment of vinylaluminums that are otherwise not easily accessible. The derived α-vinyl halides and boronates can be synthesized through direct treatment with the appropriate electrophiles [e.g., Br 2 and methoxy(pinacolato)boron, respectively]. Ni-catalyzed hydroaluminations can be performed with as little as 0.1 mol % catalyst and on gram scale with equally high efficiency and selectivity.
- Gao, Fang,Hoveyda, Amir H.
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supporting information; experimental part
p. 10961 - 10963
(2010/09/17)
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- Cross coupling in water: Suzuki-Miyaura vinylation and difluorovinylation of arylboronic acids
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A general and efficient protocol for the Suzuki-Miyaura coupling of aryl boronic acids with vinylmesylate or difluorovinylmesylate or Cl 2CCF2 in water or water/n-butanol is reported, utilizing Na2PdCl4 (1 mol%) and a highly water-soluble fluorenylphosphine (CataCXium F sulf).
- Pschierer, Jan,Peschek, Natalie,Plenio, Herbert
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experimental part
p. 636 - 642
(2010/08/20)
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- AZEPINO [4, 5-B] INDOLES AND METHODS OF USE
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This disclosure relates to new azepino[4,5-b]indole compounds that may be used to modulate a histamine receptor in an individual. Novel compounds are described, including new 1, 2,3,4,5, 6-tetrahydroazepino[4,5-b]indoles. Pharmaceutical compositions are also provided.
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Page/Page column 249-250
(2010/05/14)
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- Palladium-catalyzed cross-coupling reactions of potassium alkenyltrifluoroborates with organic halides in aqueous media
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Potassium vinyl and alkenyltrifluoroborates are cross-coupled with aryl and heteroaryl bromides using 1 mol % Pd loading of 4-hydroxyacetophenone oxime derived palladacycle or Pd(OAc)2 as precatalysts, K 2CO3 as base, and TBAB as additive and water reflux under conventional or microwave heating to afford styrenes, stilbenoids, and alkenylbenzenes. These borates can be cross-coupled diastereoselectively with allyl and benzyl chlorides using KOH as base in acetone-water (3:2) at 50°C and 0.1 mol % Pd loading, giving the corresponding 1,4-dienes and allylarenes, respectively. These simple phosphine-free reaction conditions allow the palladium recycling from the aqueous phase during up to five runs by extractive separation of the products, which contain 58-105 ppm of Pd.
- Alacid, Emilio,Najera, Carmen
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supporting information; experimental part
p. 2321 - 2327
(2009/07/18)
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- General reaction conditions for the palladium-catalyzed vinylation of aryl chlorides with potassium alkenyltrifluoroborates
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(Chemical Equation Presented) Activated and deactivated aryl and heteroaryl chlorides are efficiently cross-coupled with potassium vinyl- and alkenyltrifluoroborates using 4-hydroxyacetophenone oxime derived palladacycle as precatalyst in 1 to 3 mol % Pd loading, Binap as ligand, and Cs 2CO3 as base in DMF at 120°C. The reactions can also be performed using Pd(OAc)2 as Pd(0) source, although with lower efficiency. Bidentate ligands such as Binap and dppp can be used, the former being the best choice. Only in the case of deactivated aryl chlorides should the reaction temperature be increased to 160°C to achieve good yields. The corresponding cross-coupled compounds, such as styrenes, stilbenes, and alkenylarenes, are obtained in good yields and with high regio- and diastereoselectivity. 2009 American Chemical Society.
- Alacid, Emilio,Najera, Carmen
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supporting information; experimental part
p. 8191 - 8195
(2010/03/04)
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- Aqueous sodium hydroxide promoted cross-coupling reactions of alkenyltrialkoxysilanes under ligand-free conditions
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(Chemical Equation Presented) Fluoride-free cross-coupling reactions of alkenyltrialkoxysilanes with aryl iodides, bromides, and chlorides are performed on water using sodium hydroxide as activator at 120 °C under normal or microwave heating. This process occurs in the presence of Pd(OAc)2 or 4-hydroxyacetophenone oxime-derived palladacycle 1 as precatalysts under ligand-free conditions with low Pd loadings (0.01-1 mol %) and using tetra-n-butylammonium bromide as additive. Different commercially available vinylalkoxylsilanes can be cross-coupled under these reaction conditions to the corresponding styrenes, the best substrates being vinyltrimethoxy- or vinyltriethoxysilane. Alkenyltriethoxysilanes, prepared by Wilkinson-catalyzed hydrosilylation of alkynes with triethoxysilane, are stereospecifically arylated with aryl and vinyl halides under microwave irradiation in moderate to high β/α regioselectivity affording unsymmetrical stilbenes, alkenylbenzenes, and conjugate dienes, respectively. This simple procedure allows the palladium recycling from the aqueous phase during three runs by extractive separation of the products, which contain very low levels of Pd (21-27.5 ppm for an aryl iodide and up to 76 ppm for a bromide).
- Alacid, Emilio,Najera, Carmen
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p. 2315 - 2322
(2008/09/19)
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- Consecutive palladium-catalyzed Hiyama-Heck reactions in aqueous media under ligand-free conditions
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Symmetric and asymmetric (E)-1,2-diarylethenes are synthesized from aryl bromides by consecutive one-pot Hiyama-Heck reactions carried out in water and under air; the only additives required are sodium hydroxide, palladium acetate and poly(ethylene glycol), and the products are isolable in many cases by simple filtration of the water solution. The Royal Society of Chemistry.
- Gordillo, Alvaro,De Jesus, Ernesto,Lopez-Mardomingo, Carmen
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p. 4056 - 4058
(2008/03/14)
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- Suzuki-Miyaura cross-coupling reactions of potassium vinyltrifluoroborate with aryl and heteroaryl electrophiles
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We have previously reported that the palladium-catalyzed cross-coupling reaction of potassium vinyltrifluoroborate with aryl electrophiles proceeds with good yields. Herein, we describe recent progress in optimizing the reaction, as well as outlining the scope and limitations of the reaction. The cross-coupling reaction can generally be effected using 2 mol % of PdCl2 and 6 mol % of PPh3 as a catalyst system in THF/H2O with Cs 2CO3 as a base. Moderate to good yields are obtained in the presence of a variety of functional groups.
- Molander, Gary A.,Brown, Adam R.
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p. 9681 - 9686
(2007/10/03)
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- QUINOLONE ANTIBACTERIAL AGENTS
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Compounds of formula (I, II, III, IV, V, and VI) and methods for their preparation are disclosed. Further disclosed are methods of making biologically active compounds of formula (I) as well as pharmaceutically acceptable compositions comprising compounds of formula (I). Compounds of formula (I) as disclosed herein can be used in a variety of applications including use as antibacterial agents.
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Page/Page column 103; 104
(2010/02/11)
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- Synthesis and inhibition of Src kinase activity by 7-ethenyl and 7-ethynyl-4-anilino-3-quinolinecarbonitriles
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A series of 7-ethynyl and 7-ethenyl-4-anilino-3-quinolinecarbonitriles were synthesized and tested for Src inhibition. Derivatives bearing a C-6 methoxy group and 2,4-dichloro-5-methoxyaniline at C-4 showed optimal inhibition of Src enzymatic and cellular activity. The ethenyl and ethynyl groups were incorporated at C-7 utilizing a Stille, Heck, or Sonogashira coupling reaction.
- Barrios Sosa, Ana Carolina,Boschelli, Diane H.,Ye, Fei,Golas, Jennifer M.,Boschelli, Frank
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p. 2155 - 2158
(2007/10/03)
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- Catalysis of the β-elimination of HF from isomeric 2-fluoroethylpyridines and 1-methyl-2-fluoroethylpyridinium salts. Proton-activating factors and methyl-activating factors as a mechanistic test to distinguish between concerted E2 and E1cb irreversible mechanisms
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Second-order rate constants, kOHN, M-1 s-1, for the β-elimination reactions of HF with 2-(2-fluoroethyl)pyridine (2), 3-(2-fluoroethyl)pyridine (3), and 4-(2-fluoroethyl)pyridine (4) in OH-/H2O, at 50°C and μ = 1 M KCl, are kOHN = 0.646 × 10-4 M-1 s-1, kOHN = 2.97 × 10-6 M-1 s-1, and kOHN = 5.28 × 10-4 M-1 s-1, respectively. When compared with the second-order rate constants for the same processes with the nitrogen-methylated substrates 1-methyl-2-(2-fluoroethyl)pyridinium iodide (5), 1-methyl-3-(2-fluoroethyl)pyridinium iodide (6), and 1-methyl-4-(2-fluoroethyl)pyridinium iodide (7), the methyl-activating factor (MethylAF) can be calculated from the ratio kOHNCH3/kOHN, and a value of 8.7 × 105 is obtained with substrates 5/2, a value of 1.6 × 103 with 6/3, and a value of 2.1 × 104 with 7/4. The high values of MethylAF are in agreement with an irreversible E1cb mechanism (ANDE* + DN) for substrates 5 and 7 and with the high stability of the intermediate carbanion related to its enamine-type structure. In acetohydroxamate/acetohydroxamic acid buffers (pH 8.45-9.42) and acetate/acetic acid buffers (pH 4.13-5.13), the β-elimination reactions of HF, with substrates 2 and 4, occur at NH+, the substrates protonated at the nitrogen atom of the pyridine ring, even when the [NH+] is much lower than the [N], the unprotonated substrate, due to the high proton-activating factor (PAF) value observed: 3.6 × 105 for 2 and 6.5 × 104 for 4 with acetohydroxamate base. These high PAF values are indicative of an irreversible E1cb mechanism rather than a concerted E2 (ANDEDN) mechanism. Finally, the rate constant for carbanion formation from NH+ with 2 is kBNH+ = 0.35 M-1 s-1, which is lower than when chlorine is the leaving group (kBNH+ = 1.05 M-1 s-1; Alunni, S.; Busti, A. J. Chem. Soc., Perkin Trans. 2 2001, 778). This is direct experimental evidence that some lengthening of the carbon-leaving group bond can occur in the intermediate carbanion. This is a point of interest for interpreting a heavy-atom isotope effect.
- Alunni, Sergio,Laureti, Valeria,Ottavi, Laura,Ruzziconi, Renzo
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p. 718 - 725
(2007/10/03)
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- Inhibitors of cell proliferation, angiogenesis, fertility, and muscle contraction
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The invention concerns inhibitors of cell proliferation, angiogenesis, fertility, and muscle contraction, characterized by formula I wherein, X, Y and Z independently represent C or N; ------ is an optional double bond; n is 0 or 1; R1, R2, and R4 independently represent hydrogen, a chemical bond, C1-10 alkyl; C2-10 alkenyl; C2-10 alkinyl; aryl; aryl-C1-10 alkyl; C3-10 heterocyclyl; C5-10 heteroaryl; halo, CF3; NO2; NHC(O)R*, OR, said alkyl, alkenyl, alkinyl, aryl, arylalkyl, heterocyclyl, or heteroaryl being optionally substituted; R3, R5, and R6 independently represent hydrogen, C1-10alkyl; C2-10 alkenyl; C2-10 alkinyl; aryl; aryl-C1-10alkyl; C3-10 heterocyclyl; C5-10 heteroaryl; halo, CF3; NO2; NHC(O)R*, OR, said alkyl, alkenyl, alkinyl, aryl, heterocyclyl, or heteroaryl being optionally substituted; or R5 and R6 together form a 5- or 6-member aryl, heterocyclyl or heteroaryl group; R is hydrogen or C1-6 alkyl; R* is hydrogen, or C1-6 alkyl, or OH, wherein the optional substituents are preferably selected from the group of one to three OH, C1-6 alkyl, halo, NO2, C1-6 alkoxy, and CF3, or a pharmaceutically acceptable salt thereof.
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- Inhibitors of protein isoprenyl transferases
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Compounds having the formula or a pharmaceutically acceptable salt thereof wherein R1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L2—, and (i) heterocyclic-L2—; R2 is selected from (a) (b) —C(O)NH—CH(R14)—C(O)OR15, (c) (d) —C(O)NH—CH(R14)—C(O)NHSO2R16 (e) —C(O)NH—CH(R14)-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R14)—C(O)NR17R18; R3 is heterocyclic, aryl, substituted or unsubstituted cycloalkyl; R4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L1 is absent or is selected from (a) —L4—N(R5)—L5—, (b) —L4—O—L5—, (c) —L4—S(O)n—L5— (d) —L4-L6—C(W)—N(R5)—L5—, (e) —L4-L6—S(O)m—N(R5)—L5—, (f) —L4—N(R5)—C(W)—L7-L5—, (g) —L4—N(R5)—S(O)p—L7—L5—, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, and (j) optionally substituted alkynylene are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.
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- Synthesis and pharmacological evaluation of some (pyridyl)cyclopropylmethyl amines and their methiodides as nicotinic receptor ligands.
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A series of 3- and (4-pyridyl)cyclopropylmethyl amines and their quaternary ammonium derivatives have been synthesized; they can be considered as rigid analogues of nicotine. The compounds have been tested on rat cerebral cortex to measure the affinity for the central nicotinic receptor. Only the methiodides show affinity in the micromolar range. The results obtained can provide useful information on the topography of the nicotinic receptor-binding site.
- Guandalini, Luca,Dei, Silvia,Manetti, Dina,Romanelli, Maria Novella,Scapecchi, Serena,Teodori, Elisabetta,Varani, Katia
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p. 487 - 496
(2007/10/03)
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- Development of a polymer bound Wittig reaction and use in multi-step organic synthesis for the overall conversion of alcohols to β-hydroxyamines
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An efficient combinatorial access to β-hydroxyamines suitable for automation is achieved by the mild oxidation of alcohols to aldehydes by polymer supported perruthenate (PSP), the subsequent clean olefination of the obtained aldehydes by polymer supported Wittig reagents followed by the epoxidation of the olefins by dimethyldioxirane (DMDO), and the final aminolysis of the epoxides with various amines is described.
- Bolli, Martin H.,Ley, Steven V.
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p. 2243 - 2246
(2007/10/03)
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- A NOVEL SYNTHESIS OF 3- AND 4-ALKENYLPYRIDINES
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A new approach for the simple preparation of 3- and 4-alkenylpyridines that relys upon the palladium catalyzed cross coupling reaction of diethylpyridylboranes with vinylic bromides is described.
- Ishikura, Minoru,Kamada, Machiko,Ohta, Tsukasa,Terashima, Masanao
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p. 2475 - 2478
(2007/10/02)
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- A REGIOSPECIFIC SYNTHESIS OF CARBOSUBSTITUTED HETEROAROMATIC DERIVATIVES VIA Pd-CATALYZED CROSS COUPLING
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The Pd-catalyzed cross-coupling reaction of either heteroarylzinc derivatives with unsaturated organic halides or heteroaryl halides with organometallic reagents containing Zn or Al can produce cleanly and regiospecifically the corresponding carbo-substituted heteroatomic compounds in high yields.
- Negishi, Ei-ichi,Luo, Fen-Tair,Frisbee, Roger,Matsushita, Hajime
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p. 117 - 122
(2007/10/02)
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- Catalytic Reactions of Pyridines. IV. Heterogeneous Vapor-phase Side-chain Alkylation of Pyridines with Alcohols over Na+, K+, Rb+, and Cs+ Exchanged Zeolites
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The heterogeneous vapor-phase alkylation of pyridine with methanol over Na+, K+, Rb+, or Cs+ exchanged X- or Y-type zeolite in an atmophere of nitrogen resulted in the formation of 2- and 4-ethylpyridines and 2- and 4-vinylpyridines together with picolines and lutidines.Next, the alkylation of α-, β-, and γ-picolines with methanol was studied over alkali cation exchanged zeolites and was found to produce mainly the side-chain methylated derivatives: ethylpyridines and vinylpyridines.However, considerable amounts of ring-alkylated derivatives (lutidines) were formed simultaneously.In general, the catalytic activity became observable under reaction conditions involving both a high temperature and a small flow rate of carrier gas (N2).The yields of ethylpyridines were highest when the CsY catalyst was used at 450 deg C, whereas the yields of vinylpyridines were highest when the CsX catalyst was used at 425 deg C.This catalytic side-chain alkylation over alkali cation exchanged zeolites was successfully applied to a variety of picolines, lutidines, and ethylpyridines with either methanol or ethanol.
- Kashiwagi, Hiroshi,Enomoto, Saburo
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p. 404 - 411
(2007/10/02)
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