- Asymmetric conjugate addition reaction using pyrazole derivatives as a chiral catalyst
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The conjugate addition of Grignard reagent (2) onto 1-(α,β -unsaturated)acyl 3,5-dimethylpyrazole (1) was enantioselectively catalyzed by the copper complex from cuprous compounds and 3-phenyl-l-menthopyrazole (3).
- Kashima, Choji,Yokoyama, Hiroyo,Shibata, Saori,Fujisawa, Kiyoshi,Nishio, Takehiko
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Read Online
- Pd(II)-Catalyzed Pyridine N -Oxides Directed Arylation of Unactivated Csp3-H Bonds
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A novel Pd(II)-catalyzed pyridine N-oxide directed remote arylation of unactivated Csp3-H bonds in aliphatic amides with aryl iodides has been developed. This protocol allows installing various aryl groups at the β- or γ-Csp3 atom of alkyl carboxylic acid amides. The key palladabicyclic intermediate of this transformation has been identified by HR-MS and 1H NMR method. (Chemical Equation Presented).
- Liu, Jianzhong,Xie, Ying,Zeng, Wei,Lin, Dongen,Deng, Yuanfu,Lu, Xiaoxia
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- Efficient asymmetric transfer hydrogenation of activated olefins catalyzed by ruthenium amido complexes
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The asymmetric transfer hydrogenation of activated olefins with chiral ruthenium amido complexes (Noyori catalyst) using formic acid-triethylamine azeotrope as hydrogen source resulted in excellent yields and high enantioselectivities (up to 88.5%).
- Chen, Ying-Chun,Xue, Dong,Deng, Jin-Gen,Cui, Xin,Zhu, Jin,Jiang, Yao-Zhong
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Read Online
- Chemoselective reduction of ?,¢-unsaturated carbonyl and carboxylic compounds by hydrogen iodide
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The selective reduction of ?,¢-unsaturated carbonyl compounds was achieved to produce saturated carbonyl compounds with aqueous HI solution. The introduction of an aryl group at an ? or ¢ position efficiently facilitated the reduction with good yield. The reaction was applicable to compounds bearing carboxylic acids and halogen atoms. Through the investigation of the reaction mechanism, it was found that Michael-type addition of iodide occurred to produce ¢-iodo compounds followed by the reduction of C-I bond via anionic and radical paths.
- Matsumoto, Shoji,Marumoto, Hayato,Akazome, Motohiro,Otani, Yasuhiko,Kaiho, Tatsuo
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p. 590 - 599
(2021/03/29)
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- Asymmetric conjugate addition reactions with chiral oxadiazinones: Unusual conformational properties of the oxadiazinones
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A series of Ephedra based oxadiazinones have been prepared, acylated, and examined in the asymmetric conjugate addition reaction with Grignard reagents in the presence of copper(I) bromide-dimethyl sulfide complex. The highest diastereoselectivity that was obtained in the conjugate addition reaction was observed with the (1R,2S)-ephedrine based N4-methyloxadiazinone (5:1 d.r.) favoring the formation of the (S)-configuration of the conjugate addition product. Efforts to enhance the level of diastereoselection via increasing the steric volume of the stereo-directing N4-substituent of the oxadiazinone (N4- = p-methoxyphenyl or -isopropyl) led to an observed decrease in the level of diastereoselection. A computational study was conducted to examine the conformations adopted by the N4-methyloxadiazinone vs. the N4-isopropyl-oxadiazinone that yielded the lower diastereoselectivity. An argument is made for the stereoelectronic properties of the N4-substituent being the cause of both the moderate diastereoselectivity and the unexpected facial preference for the conjugate addition.
- Obe, Fatima Olayemi,Davis, Ryan A.,Spurlock, Jennifer,Grunloh Barnes, Morgan M.,Lindvall, Tyler,Wendorf, Micah S.,Delach, Christina,Ferrence, Gregory M.,Standard, Jean M.,Hitchcock, Shawn R.
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- Photoredox Activation of Formate Salts: Hydrocarboxylation of Alkenes via Carboxyl Group Transfer
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A photoredox activation mode of formate salts for carboxylation was developed. Using a formate salt as the reductant, carbonyl source, and hydrogen atom transfer reagent, a wide range of alkenes can be converted into acid products via a carboxyl group tra
- Huang, Yan,Hou, Jing,Zhan, Le-Wu,Zhang, Qian,Tang, Wan-Ying,Li, Bin-Dong
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p. 15004 - 15012
(2021/12/14)
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- Photoinduced Hydrocarboxylation via Thiol-Catalyzed Delivery of Formate across Activated Alkenes
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Herein we disclose a new photochemical process to prepare carboxylic acids from formate salts and alkenes. This redox-neutral hydrocarboxylation proceeds in high yields across diverse functionalized alkene substrates with excellent regioselectivity. This operationally simple procedure can be readily scaled in batch at low photocatalyst loading (0.01% photocatalyst). Furthermore, this new reaction can leverage commercially available formate carbon isotologues to enable the direct synthesis of isotopically labeled carboxylic acids. Mechanistic studies support the working model involving a thiol-catalyzed radical chain process wherein the atoms from formate are delivered across the alkene substrate via CO2?- as a key reactive intermediate.
- Alektiar, Sara N.,Wickens, Zachary K.
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supporting information
p. 13022 - 13028
(2021/09/03)
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- Synthesis method of succinic acid derivative or 3 -arylpropionic acid (by machine translation)
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The invention discloses a synthesis method of a succinic acid derivative or 3 -arylpropionic acid, which comprises the following steps: adding a base in a drying reaction tube and CO removing CO. 2 The reaction is carried out under the irradiation of visible light, the reaction is carried out under visible light irradiation, and then separation and purification are carried out to obtain the butanedioic acid derivative or 3 -arylpropionic acid product; the base comprises sodium tert-butoxide, potassium tert-butoxide, lithium tert-butyl alcohol and 4 - potassium carbonate; and the reaction substrate comprises an acrylate compound or an aryl vinyl compound. CO can be induced by visible light. 2 The scheme provided by the invention is mild in reaction condition and wide in reaction 3 - substrate selectivity, and the reaction substrate is wide in selectivity, the raw materials are cheap and easily available, and the method has a good industrial application prospect. (by machine translation)
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Paragraph 0101-0114; 0115; 0151
(2020/10/30)
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- Cobalt-Catalyzed Asymmetric Hydrogenation of α,β-Unsaturated Carboxylic Acids by Homolytic H2 Cleavage
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The asymmetric hydrogenation of α,β-unsaturated carboxylic acids using readily prepared bis(phosphine) cobalt(0) 1,5-cyclooctadiene precatalysts is described. Di-, tri-, and tetra-substituted acrylic acid derivatives with various substitution patterns as well as dehydro-α-amino acid derivatives were hydrogenated with high yields and enantioselectivities, affording chiral carboxylic acids including Naproxen, (S)-Flurbiprofen, and a d-DOPA precursor. Turnover numbers of up to 200 were routinely obtained. Compatibility with common organic functional groups was observed with the reduced cobalt(0) precatalysts, and protic solvents such as methanol and isopropanol were identified as optimal. A series of bis(phosphine) cobalt(II) bis(pivalate) complexes, which bear structural similarity to state-of-the-art ruthenium(II) catalysts, were synthesized, characterized, and proved catalytically competent. X-band EPR experiments revealed bis(phosphine)cobalt(II) bis(carboxylate)s were generated in catalytic reactions and were identified as catalyst resting states. Isolation and characterization of a cobalt(II)-substrate complex from a stoichiometric reaction suggests that alkene insertion into the cobalt hydride occurred in the presence of free carboxylic acid, producing the same alkane enantiomer as that from the catalytic reaction. Deuterium labeling studies established homolytic H2 (or D2) activation by Co(0) and cis addition of H2 (or D2) across alkene double bonds, reminiscent of rhodium(I) catalysts but distinct from ruthenium(II) and nickel(II) carboxylates that operate by heterolytic H2 cleavage pathways.
- Chirik, Paul J.,Shevlin, Michael,Zhong, Hongyu
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supporting information
(2020/03/13)
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- Folding Assessment of Incorporation of Noncanonical Amino Acids Facilitates Expansion of Functional-Group Diversity for Enzyme Engineering
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Protein design is limited by the diversity of functional groups provided by the canonical protein ?building blocks“. Incorporating noncanonical amino acids (ncAAs) into enzymes enables a dramatic expansion of their catalytic features. For this, quick identification of fully translated and correctly folded variants is decisive. Herein, we report the engineering of the enantioselectivity of an esterase utilizing several ncAAs. Key for the identification of active and soluble protein variants was the use of the split-GFP method, which is crucial as it allows simple determination of the expression levels of enzyme variants with ncAA incorporations by fluorescence. Several identified variants led to improved enantioselectivity or even inverted enantiopreference in the kinetic resolution of ethyl 3-phenylbutyrate.
- Drienovská, Ivana,Gajdo?, Matú?,Kindler, Alexia,Takhtehchian, Mahsa,Darnhofer, Barbara,Birner-Gruenberger, Ruth,D?rr, Mark,Bornscheuer, Uwe T.,Kourist, Robert
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supporting information
p. 12338 - 12342
(2020/09/07)
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- CuH-Catalyzed Asymmetric Reductive Amidation of α,β-Unsaturated Carboxylic Acids
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The direct enantioselective copper hydride (CuH)-catalyzed synthesis of β-chiral amides from α,β-unsaturated carboxylic acids and secondary amines under mild reaction conditions is reported. The method utilizes readily accessible carboxylic acids and tolerates a variety of functional groups in the β-position including several heteroarenes. A subsequent iridium-catalyzed reduction to γ-chiral amines can be performed in the same flask without purification of the intermediate amides.
- Link, Achim,Zhou, Yujing,Buchwald, Stephen L.
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supporting information
p. 5666 - 5670
(2020/07/24)
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- Ligand-Controlled Regiodivergence in Nickel-Catalyzed Hydroarylation and Hydroalkenylation of Alkenyl Carboxylic Acids**
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A nickel-catalyzed regiodivergent hydroarylation and hydroalkenylation of unactivated alkenyl carboxylic acids is reported, whereby the ligand environment around the metal center dictates the regiochemical outcome. Markovnikov hydrofunctionalization products are obtained under mild ligand-free conditions, with up to 99 % yield and >20:1 selectivity. Alternatively, anti-Markovnikov products can be accessed with a novel 4,4-disubstituted Pyrox ligand in excellent yield and >20:1 selectivity. Both electronic and steric effects on the ligand contribute to the high yield and selectivity. Mechanistic studies suggest a change in the turnover-limiting and selectivity-determining step induced by the optimal ligand. DFT calculations reveal that in the anti-Markovnikov pathway, repulsion between the ligand and the alkyl group is minimized (by virtue of it being 1° versus 2°) in the rate- and regioselectivity-determining transmetalation transition state.
- Deng, Ruohan,Engle, Keary M.,Fu, Yue,Gao, Yang,Li, Zi-Qi,Liu, Peng,Tran, Van T.
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supporting information
p. 23306 - 23312
(2020/10/19)
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- Construction of enantioenriched 9H-Fluorene frameworks via a cascade reaction involving remote vinylogous dynamic kinetic resolution
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The benzylic C-H group of α,α-dicyanoolefins from 3-substituted 1-indanones could be significantly activated via transmission along the aromatic system, thus enabling dynamic kinetic resolution via a traditional reversible deprotonation- protonation process. Enantioenriched 9-substituted 9H-fluorene frameworks were finally constructed through an asymmetric vinylogous Michael addition to nitroolefins, followed by a cascade cyclization and oxidative aromatization process, under the catalysis of a chiral bifunctional thiourea-tertiary amine.
- Hu, Cui-Xia,Chen, Lin,Hu, Di,Song, Xue,Chen, Zhi-Chao,Du, Wei,Chen, Ying-Chun
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supporting information
p. 8973 - 8977
(2020/11/30)
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- Harnessing Applied Potential: Selective β-Hydrocarboxylation of Substituted Olefins
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The construction of carboxylic acid compounds in a selective fashion from low value materials such as alkenes remains a long-standing challenge to synthetic chemists. In particular, β-addition to styrenes is underdeveloped. Herein we report a new electrosynthetic approach to the selective hydrocarboxylation of alkenes that overcomes the limitations of current transition metal and photochemical approaches. The reported method allows unprecedented direct access to carboxylic acids derived from β,β-trisubstituted alkenes, in a highly regioselective manner.
- Alkayal, Anas,Buckley, Benjamin R.,Malkov, Andrei V.,Montanaro, Stephanie,Tabas, Volodymyr,Wright, Iain A.
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supporting information
(2020/02/13)
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- Exploration of New Biomass-Derived Solvents: Application to Carboxylation Reactions
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A range of hitherto unexplored biomass-derived chemicals have been evaluated as new sustainable solvents for a large variety of CO2-based carboxylation reactions. Known biomass-derived solvents (biosolvents) are also included in the study and the results are compared with commonly used solvents for the reactions. Biosolvents can be efficiently applied in a variety of carboxylation reactions, such as Cu-catalyzed carboxylation of organoboranes and organoboronates, metal-catalyzed hydrocarboxylation, borocarboxylation, and other related reactions. For many of these reactions, the use of biosolvents provides comparable or better yields than the commonly used solvents. The best biosolvents identified are the so far unexplored candidates isosorbide dimethyl ether, acetaldehyde diethyl acetal, rose oxide, and eucalyptol, alongside the known biosolvent 2-methyltetrahydrofuran. This strategy was used for the synthesis of the commercial drugs Fenoprofen and Flurbiprofen.
- Gevorgyan, Ashot,Hopmann, Kathrin H.,Bayer, Annette
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p. 2080 - 2088
(2020/02/20)
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- Development of alkyl glycerone phosphate synthase inhibitors: Structure-activity relationship and effects on ether lipids and epithelial-mesenchymal transition in cancer cells
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In aggressive tumors, alkylglyceronephosphate synthase (AGPS) controls cellular ether phospholipid utilization and metabolism to promote cancer cell proliferation and motility. SAR studies on the first-in-class AGPS inhibitor 1, discovered by our group, led to the 2,6-difluoro analog 2i which showed higher binding affinity than 1 in vitro. In 231MFP cancer cells, 2i reduced ether lipids levels and cell migration rate. When tested in PC-3 and MDA-MB-231 cancer cells, 2i specifically impaired epithelial to mesenchymal transition (EMT) by modulating E-cadherin, Snail and MMP2 expression levels. Moreover, the combination of siRNAs against AGPS and 2i provided no additive effect, confirming that the modulation of 2i on EMT specifically relies on AGPS inhibition. Finally, this compound also affected cancer cell proliferation especially in MDA-MB-231 cells expressing higher AGPS level, whereas it provided negligible effects on MeT5A, a non-tumorigenic cell line, thus showing cancer specificity.
- Stazi, Giulia,Battistelli, Cecilia,Piano, Valentina,Mazzone, Roberta,Marrocco, Biagina,Marchese, Sara,Louie, Sharon M.,Zwergel, Clemens,Antonini, Lorenzo,Patsilinakos, Alexandros,Ragno, Rino,Viviano, Monica,Sbardella, Gianluca,Ciogli, Alessia,Fabrizi, Giancarlo,Cirilli, Roberto,Strippoli, Raffaele,Marchetti, Alessandra,Tripodi, Marco,Nomura, Daniel K.,Mattevi, Andrea,Mai, Antonello,Valente, Sergio
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p. 722 - 735
(2019/01/04)
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- Synthesis of Carboxylic Acids by Palladium-Catalyzed Hydroxycarbonylation
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The synthesis of carboxylic acids is of fundamental importance in the chemical industry and the corresponding products find numerous applications for polymers, cosmetics, pharmaceuticals, agrochemicals, and other manufactured chemicals. Although hydroxycarbonylations of olefins have been known for more than 60 years, currently known catalyst systems for this transformation do not fulfill industrial requirements, for example, stability. Presented herein for the first time is an aqueous-phase protocol that allows conversion of various olefins, including sterically hindered and demanding tetra-, tri-, and 1,1-disubstituted systems, as well as terminal alkenes, into the corresponding carboxylic acids in excellent yields. The outstanding stability of the catalyst system (26 recycling runs in 32 days without measurable loss of activity), is showcased in the preparation of an industrially relevant fatty acid. Key-to-success is the use of a built-in-base ligand under acidic aqueous conditions. This catalytic system is expected to provide a basis for new cost-competitive processes for the industrial production of carboxylic acids.
- Sang, Rui,Kucmierczyk, Peter,Dühren, Ricarda,Razzaq, Rauf,Dong, Kaiwu,Liu, Jie,Franke, Robert,Jackstell, Ralf,Beller, Matthias
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supporting information
p. 14365 - 14373
(2019/09/06)
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- OPIOID RECEPTOR MODULATORS AND PRODUCTS AND METHODS RELATED THERETO
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Compounds are provided having the structure of Formula (I): or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein A, B, L, R3, R4, R5, R6, R8, m and n are as defined herein. Such compounds modulate the opioid receptor, particulare the mu-opioid receptor (MOR) and/or the kappa-opioid receptor (KOR), and/or the delta-opioid receptor (DOR). Products containing such compounds, as well as methods for their use and preparation, are also provided.
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- Identification of an Esterase Isolated Using Metagenomic Technology which Displays an Unusual Substrate Scope and its Characterisation as an Enantioselective Biocatalyst
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Evaluation of an esterase annotated as 26D isolated from a marine metagenomic library is described. Esterase 26D was found to have a unique substrate scope, including synthetic transformations which could not be readily effected in a synthetically useful manner using commercially available enzymes. Esterase 26D was more selective towards substrates which had larger, more sterically demanding substituents (i. e. iso-propyl or tert-butyl groups) on the β-carbon, which is in contrast to previously tested commercially available enzymes which displayed a preference for substrates with sterically less demanding substituents (e.g. methyl group) at the β-carbon. (Figure presented.).
- Gavin, Declan P.,Murphy, Edel J.,Foley, Aoife M.,Castilla, Ignacio Abreu,Reen, F. Jerry,Woods, David F.,Collins, Stuart G.,O'Gara, Fergal,Maguire, Anita R.
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p. 2466 - 2474
(2019/03/11)
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- Catalytic Transfer Hydrodebenzylation with Low Palladium Loading
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A highly-efficient catalytic system for hydrodebenzylation reaction is described. The cleavage of O-benzyl and N-benzyl protecting groups was performed using an uncommonly low palladium loading (0.02–0.3 mol%; TON up to 5000) in a relatively short reaction time. The approach was used for a variety of substrates including pharmaceutically important precursors, and gram-scale deprotection reaction was shown. Transfer conditions together with easy-to-make Pd/C catalyst are the key features of this debenzylation scheme. (Figure presented.).
- Yakukhnov, Sergey A.,Ananikov, Valentine P.
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supporting information
p. 4781 - 4789
(2019/09/16)
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- Pd-Catalyzed Highly Chemo- And Regioselective Hydrocarboxylation of Terminal Alkyl Olefins with Formic Acid
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An efficient Pd-catalyzed hydrocarboxylation of alkenes with HCOOH is described. A wide variety of linear carboxylic acids bearing various functional groups can be obtained with excellent chemo- and regioselectivities under mild reaction conditions. The reaction process is operationally simple and requires no handling of toxic CO.
- Ren, Wenlong,Chu, Jianxiao,Sun, Fei,Shi, Yian
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supporting information
p. 5967 - 5970
(2019/08/26)
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- Synthetic method of terminal carboxylic acid
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The invention discloses a synthetic method of a terminal carboxylic acid. The synthetic method is characterized by comprising the steps of adding an olefin represented by a formula (3) shown in the description, formic acid, acetic anhydride, Pd(OAc)2 and a monophosphorus ligand TFPP into an organic solvent in a proportion, carrying out hydrogen carbonylation reaction on the olefin represented by the formula (3) shown in the description, formic acid and acetic anhydride at 80-90 DEG C for 48h-72h under the catalysis of the metal palladium salt Pd(OAc)2 and the monophosphorus ligand TFPP so as to obtain the terminal carboxylic acid represented by a formula shown in the description, and separating a target product, namely the terminal carboxylic acid after the reaction is finished, wherein olefin represented by the formula (3) is selected from cycloolefins, or linear olefins of which the R1 is electron donating groups. By virtue of the method disclosed by the invention, corresponding terminal carboxylic acid and a derivative thereof can be prepared through the reaction under mild conditions of low temperature and no high pressure; and the steps of the synthetic method are simple and convenient, the operation is convenient, the yield is high, the energy source can be greatly saved, and the synthetic efficiency can be greatly improved.
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Paragraph 0107-0110
(2019/11/21)
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- Regioselectivity inversion tuned by iron(iii) salts in palladium-catalyzed carbonylations
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Impactful regioselectivity control is crucial for cost-effective chemical synthesis. By using cheap and abundant iron(iii) salts, the hydroxycarbonylations of both aromatic and aliphatic alkenes were significantly enhanced in both reactivity and selectivity (iso/n or n/iso up to >99:1). Moreover, Pd-catalyzed carbonylation selectivity can be switched from branched to linear by using different Fe(iii) salts. In addition, similar results were obtained for the carbonylation of secondary alcohols.
- Huang, Zijun,Cheng, Yazhe,Chen, Xipeng,Wang, Hui-Fang,Du, Chen-Xia,Li, Yuehui
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supporting information
p. 3967 - 3970
(2018/04/23)
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- Enantioselective Hydroamidation of Enals by Trapping of a Transient Acyl Species
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An enantioselective synthesis of β-chiral amides through asymmetric and redox-neutral hydroamidation of enals is reported. In this reaction, a chiral N-heterocyclic carbene (NHC) catalyst reacts with enals to generate the homoenolate intermediate. Upon highly enantioselective β-protonation through proton-shuttle catalysis, the resulting azolium intermediate reacts with imidazole to yield the key β-chiral acyl species. This transient intermediate provides access to diversified β-chiral carbonyl derivatives, such as amides, hydrazides, acids, esters, and thioesters. In particular, β-chiral amides can be prepared in excellent yield and ee (40 chiral amides, up to 95 % yield and 99 % ee). This modular strategy overcomes the challenge of disruption of the highly selective proton-shuttling process by basic amines.
- Yuan, Pengfei,Chen, Jiean,Zhao, Jing,Huang, Yong
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supporting information
p. 8503 - 8507
(2018/07/14)
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- Cationic Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids in aqueous media
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An in-situ generated cationic Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids in water was developed and optimized. For most substrates, nearly quantitative yields were given, and the products can be purified by simple washing without column chromatography. The reaction can be scaled up to 1.0 g easily with excellent yields. Also the loading of catalyst can be lowered to 1.0 mol% with modest yields, and the reaction provided a mild and easy way to synthesize β-disubstituted carboxylic acids.
- Ni, Yuxin,Song, Kaixuan,Shen, Kai,Yang, Zhenyu,Liu, Rui,Lin, Shaohui,Pan, Qinmin
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supporting information
p. 1192 - 1195
(2018/03/01)
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- Direct β-Selective Hydrocarboxylation of Styrenes with CO2 Enabled by Continuous Flow Photoredox Catalysis
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The direct β-selective hydrocarboxylation of styrenes under atmospheric pressure of CO2 has been developed using photoredox catalysis in continuous flow. The scope of this methodology was demonstrated with a range of functionalized terminal styrenes, as well as α-substituted and β-substituted styrenes.
- Seo, Hyowon,Liu, Aofei,Jamison, Timothy F.
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supporting information
p. 13969 - 13972
(2017/10/17)
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- Pd(II)/Bipyridine-Catalyzed Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Carboxylic Acids. Synthesis of β-Quaternary Carbons Substituted Carboxylic Acids
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Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids (including β,β-disubstituted acrylic acids) was developed and optimized, which provided a mild and convenient method for the highly challenging synthesis of β-quaternary carbons substituted carboxylic acids.
- Liu, Rui,Yang, Zhenyu,Ni, Yuxin,Song, Kaixuan,Shen, Kai,Lin, Shaohui,Pan, Qinmin
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p. 8023 - 8030
(2017/08/14)
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- ANTI-HCMV COMPOSITIONS AND METHODS
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This document relates to compounds useful as agents for preventing or treating human cytomegalovirus (HCMV) infections.
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Page/Page column 79; 80
(2016/06/06)
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- Enantioselective Hydrogenation of β,β-Disubstituted Unsaturated Carboxylic Acids under Base-Free Conditions
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An additive-free enantioselective hydrogenation of β,β-disubstituted unsaturated carboxylic acids catalyzed by the Rh-(R,R)-f-spiroPhos complex has been developed. Under mild conditions, a wide scope of β,β-disubstituted unsaturated carboxylic acids were hydrogenated to the corresponding chiral carboxylic acids with excellent enantioselectivities (up to 99.3% ee). This methodology was also successfully applied to the synthesis of the pharmaceutical molecule indatraline.
- Yan, Qiaozhi,Kong, Duanyang,Zhao, Wei,Zi, Guofu,Hou, Guohua
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p. 2070 - 2077
(2016/03/15)
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- Design and Synthesis of 2-Methyl-7-aminobenzoxazole as Auxiliary in the Palladium(II)-Catalyzed Arylation of a beta-Positioned C(sp3)-H Bond
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A palladium(II)-catalyzed direct arylation of methylene C(sp3)-H bonds by 2-methyl-7-aminobenzoxazole as an effective auxiliary is reported. This process exhibited high beta-site selectivity, broad substrate scope, and compatibility with different functional groups with moderate to high yields up to 89%.
- Luo, Feihua,Yang, Jun,Li, Zhengkai,Xiang, Haifeng,Zhou, Xiangge
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supporting information
p. 887 - 893
(2016/04/05)
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- An atom-economic approach to carboxylic acids via Pd-catalyzed direct addition of formic acid to olefins with acetic anhydride as a co-catalyst
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An effective Pd-catalyzed hydrocarboxylation of olefins using formic acid with acetic anhydride as a co-catalyst is described. A variety of carboxylic acids are obtained in good yields with high regioselectivities under mild reaction conditions without the use of toxic CO gas.
- Wang, Yang,Ren, Wenlong,Shi, Yian
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supporting information
p. 8416 - 8419
(2015/08/06)
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- Development of modifiable bidentate amino oxazoline directing group for Pd-catalyzed arylation of secondary C-H bonds
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Abstract A novel bidentate α-amino oxazolinyl directing group has been developed. Different from previous directing groups, this newly designed directing group was easily prepared from amino acids and modified in structure. This auxiliary preferentially effects functionalization at secondary C(sp3)-H bonds, rather than at aryl C(sp2)-H bonds. The diastereoselectivity of direct arylation between geminal secondary C(sp3)-H bonds in linear molecules has also been realized for the first time with a chiral directing group by remote chirality relay. Two diastereoisomers are produced with the same chiral source by changing the substituents of substrates and aryl halides. A new direction: A multifunctional amino oxazoline directing group that is readily available from amino acids, has been developed, which can induce chemo-, regio- and diastereoselectivity in secondary C(sp3)-H arylation reactions. Furthermore, this directing group is removable and modifiable. Steric control and counterions play important roles in the relayed chirality transfer.
- Chen, Kang,Li, Zhao-Wei,Shen, Peng-Xiang,Zhao, Hong-Wei,Shi, Zhang-Jie
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supporting information
p. 7389 - 7393
(2015/05/13)
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- Enzyme cascade reactions: Synthesis of furandicarboxylic acid (FDCA) and carboxylic acids using oxidases in tandem
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A one-pot tandem enzyme reaction using galactose oxidase M3-5 and aldehyde oxidase PaoABC was used to convert hydroxymethylfurfural (HMF) to the pure bioplastics precursor FDCA in 74% isolated yield. A range of alcohols was also converted to carboxylic acids in high yield under mild conditions.
- McKenna, Shane M.,Leimkühler, Silke,Herter, Susanne,Turner, Nicholas J.,Carnell, Andrew J.
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supporting information
p. 3271 - 3275
(2015/06/25)
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- Facile palladium-catalyzed hydrocarboxylation of olefins without external CO gas
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An effective Pd-catalyzed hydrocarboxylation of olefins with phenyl formate and formic acid is described. A variety of carboxylic acids are obtained in good yields with high regioselectivities under operationally simple conditions without the use of toxic CO gas.
- Wang, Yang,Ren, Wenlong,Li, Jingfu,Wang, Haining,Shi, Yian
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supporting information
p. 5960 - 5963
(2015/02/19)
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- Influence of the position of the substituent on the efficiency of lipase-mediated resolutions of 3-aryl alkanoic acids
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Hydrolase-catalysed kinetic resolutions to provide enantioenriched α-substituted 3-aryl alkanoic acids are described. (S)-2-Methyl-3- phenylpropanoic acid (S)-1a was prepared in 96% ee by Pseudomonas fluorescens catalysed ester hydrolysis, while, Candida antarctica lipase B (immob) resolved the α-ethyl substituted 3-arylalkanoic acid (R)-1b in 82% ee. The influence of the position of the substituent relative to the ester site on the efficiency and enantioselectivity of the biotransformation is also explored; the same lipases were found to resolve both the α- and β-substituted alkanoic acids. Furthermore, the steric effect of substituents at the C2 stereogenic centre relative to that for their C3 substituted counterparts on the efficiency and stereoselectivity is discussed.
- Deasy, Rebecca E.,Moody, Thomas S.,Maguire, Anita R.
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p. 1480 - 1487
(2013/12/04)
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- Rhodium(I)-catalyzed enantioselective hydrogenation of substituted acrylic acids with sterically similar β,β-diaryls
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Distinct differentiation: β,β-Disubstituted acrylic acids with sterically similar geminal diaryl groups can be hydrogenated with excellent enantioselectivities in the presence of a RhI complex formed in situ with two-component ligands, a chiral secondary phosphine oxide (SPO) and an achiral phosphine (Ph3P). The sense of asymmetric induction was found to be controlled by the substrate configuration, thus allowing access to both enantiomers of the product with the same catalyst. Copyright
- Li, Yang,Dong, Kaiwu,Wang, Zheng,Ding, Kuiling
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supporting information
p. 6748 - 6752
(2013/07/26)
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- Catalytic transformation of alcohols to carboxylic acid salts and H 2 using water as the oxygen atom source
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The oxidation of alcohols to carboxylic acids is an important industrial reaction used in the synthesis of bulk and fine chemicals. Most current processes are performed by making use of either stoichiometric amounts of toxic oxidizing agents or the use of pressurized dioxygen. Here, we describe an alternative dehydrogenative pathway effected by water and base with the concomitant generation of hydrogen gas. A homogeneous ruthenium complex catalyses the transformation of primary alcohols to carboxylic acid salts at low catalyst loadings (0.2 mol%) in basic aqueous solution. A consequence of this finding could be a safer and cleaner process for the synthesis of carboxylic acids and their derivatives at both laboratory and industrial scales.
- Balaraman, Ekambaram,Khaskin, Eugene,Leitus, Gregory,Milstein, David
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p. 122 - 125
(2013/08/24)
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- NOVEL COMPOUND, AND KINESIN SPINDLE PROTEIN INHIBITOR AND APPLICATION THEREOF
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A compound represented by the following General Formula (I): where, in General Formula (I), R1 and R2 each represent an alkyl group which may have a substituent, R3 represents the following General Formula (II) or (III), and R1 and R2 may be identical or different, where, in General Formulas (II) and (III), X represents a hydrogen atom or a halogen atom, R4 represents a methyl group, a dimethyl group or an oxygen atom, and * represents a binding position.
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Paragraph 0154
(2013/10/22)
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- COMPOUND, KINESIN SPINDLE PROTEIN INHIBITOR, AND APPLICATION THEREOF
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A compound represented by the following General Formula (I): where, in General Formula (I), R1 and R2 each represent an alkyl group which may have a substituent, R3 represents the following General Formula (II) or (III), and R1 and R2 may be identical or different, where, in General Formulas (II) and (III), X represents a hydrogen atom or a halogen atom, R4 represents a methyl group, a dimethyl group or an oxygen atom, and * represents a binding position.
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Paragraph 0169
(2013/12/04)
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- Ruthenium-catalyzed asymmetric transfer hydrogenation of allylic alcohols by an enantioselective isomerization/transfer hydrogenation mechanism
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Reducing hazards: A asymmetric transfer hydrogen reaction was developed to reduce prochiral allylic alcohols in high yield and excellent enantioselectivity (see example). Mechanistic studies indicate a novel enantioselective isomerization/transfer hydrogenation mechanism. This new reaction is much safer than high-pressure hydrogenation using H2 gas. Copyright
- Wu, Ruoqiu,Beauchamps, Marie G.,Laquidara, Joseph M.,Sowa Jr., John R.
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p. 2106 - 2110
(2012/04/11)
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- Enantioselective oxidation of aldehydes catalyzed by alcohol dehydrogenase
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Teaching old dogs new tricks: Alcohol dehydrogenases (ADHs) may be established redox biocatalysts but they still are good for a few surprises. ADHs can be used to oxidize aldehydes, and this was demonstrated by the oxidative dynamic kinetic resolution of profens. In the presence of a suitable cofactor regeneration system, this reaction can occur with high selectivity. Copyright
- K?nst, Paul,Merkens, Hedda,Kara, Selin,Kochius, Svenja,Vogel, Andreas,Zuhse, Ralf,Holtmann, Dirk,Arends, Isabel W. C. E.,Hollmann, Frank
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p. 9914 - 9917
(2012/11/13)
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- METAL-CATALYSED CARBONYLATION OF UNSATURATED COMPOUNDS
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The invention provides a method for the hydroxycarbonylation, alkoxycarbonylation, aryloxycarbonylation or thiocarbonylation of an unsaturated molecule. The method includes a hydroxycarbonylation, alkoxycarbonylation, aryloxycarbonylationor thiocarbonylation reaction on the unsaturated molecule in which a complex including a ligand comprising a [n,n′]cyclophane comprising two non-fused monocyclic aromatic rings bridged by two linear and aliphatic linkages, in which each of the non-fused monocyclic aromatic rings is substituted with a phosphorus atom-containing substituent, is used to catalyse the reaction.
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Page/Page column 12-13
(2012/07/27)
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- Preparation of α-amino acids by oxidative oxazoline-oxazinone rearrangement-hydrogenation (OOOH). Scope and limitations
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The range and scope of the oxidative oxazoline-oxazinone rearrangement-hydrogenation sequence (OOOH)-a short, direct asymmetric synthesis of α-amino acids from carboxylic acids-was explored. The highest yet reported diastereoselectivity for hydrogenation of the oxazinone C=N bond (d.r.=>80:1) is disclosed and rationalized with the aid of ab initio molecular calculations.
- Liu, Chaomin,Molinski, Tadeusz F.
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p. 2022 - 2027
(2011/11/29)
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- A combination of in vivo selection and cell sorting for the identification of enantioselective biocatalysts
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The "carrot and stick" principle could be combined with cell sorting to enable the selection of enantioselective esterase variants from a mutant library. Hence, the enormous diversity generated in directed evolution experiments is now easily accessible by this high-throughput system. In line with the principle, the hydrolysis of 1 glycerin supports cell growth, whereas the hydrolysis of 2 leads to cell death. Copyright
- Fernandez-Alvaro, Elena,Snajdrova, Radka,Jochens, Helge,Davids, Timo,Boettcher, Dominique,Bornscheuer, Uwe T.
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supporting information; experimental part
p. 8584 - 8587
(2011/11/07)
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- Lipase catalysed kinetic resolutions of 3-aryl alkanoic acids
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Hydrolase catalysed kinetic resolutions leading to a series of 3-aryl alkanoic acids (≥94% ee) are described. Hydrolysis of the ethyl esters with a series of hydrolases was undertaken to identify biocatalysts that yield the corresponding acids with excellent enantiopurity in each case. Steric and electronic effects on the efficiency and enantioselectivity of the biocatalytic transformation were also explored.
- Deasy, Rebecca E.,Brossat, Maude,Moody, Thomas S.,Maguire, Anita R.
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- METAL CATALYSED CARBONYLATION OF UNSATURATED COMPOUNDS
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The invention provides a method for the hydroxycarbonylation, alkoxycarbonylation, aryloxycarbonylation or thiocarbonylation of an unsaturated molecule comprising effecting a hydroxycarbonylation, alkoxycarbonylation, aryloxycarbonylation or thiocarbonylation reaction on the unsaturated molecule in which a complex comprising a ligand comprising a [n,n']cyclophane comprising two non-fused monocyclic aromatic rings bridged by two linear and aliphatic linkages, in which each of the non-fused monocyclic aromatic rings is substituted with a phosphorus atom-containing substituent, is used to catalyse the hydroxycarbonylation, alkoxycarbonylation, aryloxycarbonylation or thiocarbonylation reaction.
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Page/Page column 29-30
(2011/04/18)
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- Natural diversity to guide focused directed evolution
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Simultaneous multiple site-saturation mutagenesis was performed at four active-site positions of an esterase from Pseudomonas fluorescens to improve its ability to convert 3-phenylbutyric acid esters (3-PBA) in an enantioselective manner. Based on an appropriate codon choice derived from a structural alignment of 1751 sequences of α/β-hydrolase fold enzymes, only those amino acids were considered for library creation that appeared frequently in structurally equivalent positions. Thus, the number of mutants to be screened could be substantially reduced while the number of functionally intact variants was increased. Whereas the wild-type esterase showed only marginal activity and poor enantioselectivity (Etrue=3.2) towards 3-PBA-ethyl ester, a significant number of hits with improved rates (up to 240-fold) and enantioselectivities (up to Etrue=80) were identified in these "smart" libraries.
- Jochens, Helge,Bornscheuer, Uwe T.
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experimental part
p. 1861 - 1866
(2011/11/29)
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- Chiral NG-acylated hetarylpropylguanidine-type histamine H2 receptor agonists do not show significant stereoselectivity
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A set of chiral imidazolylpropylguanidines and 2-aminothiazolylpropylguanidines bearing NG-3-phenyl- or NG-3-cyclohexylbutanoyl residues was synthesized and investigated for histamine H2 receptor (H2R) agonism (guinea pig (gp) right atrium, GTPase assay on recombinant gp and human (h)H2R) and for hH2R selectivity compared to hH1R, hH3R and hH4R. In contrast to previous studies on arpromidine derivatives, the present investigation of acylguanidine-type compounds revealed only very low eudismic ratios (1.1-3.2), indicating the stereochemistry of the acyl moiety to play only a minor role in this series of H2R agonists.
- Ghorai, Prasanta,Kraus, Anja,Birnkammer, Tobias,Geyer, Roland,Bernhardt, Günther,Dove, Stefan,Seifert, Roland,Elz, Sigurd,Buschauer, Armin
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supporting information; experimental part
p. 3173 - 3176
(2010/09/05)
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- General and practical conversion of aldehydes to homologated carboxylic acids
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(Chemical Equation Presented) The reaction of aldehydes with trichloromethide followed by sodium borohydride or sodium phenylseleno(triethyl) borate under basic conditions affords homologated carboxylic acids in high yields. This operationally simple procedure provides a practical, efficient alternative to other homologation protocols. The approach is compatible with sensitive aldehydes including enals and enolizable aldehydes. It also offers convenient access to α-monodeuterated carboxylic acids.
- Cafiero, Lauren R.,Snowden, Timothy S.
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supporting information; experimental part
p. 3853 - 3856
(2009/07/01)
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- Rh-catalyzed highly enantioselective synthesis of 3-arylbutanoic acids
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(Chemical Equation Presented) It's in the mix: The reaction conditions - catalyst, additive, and solvent - have been optimized for the asymmetric hydrogenation of 3-aryl-3-butenoic acids. The rigid, chiral bisphospholane ligand (SP,RC)-DuanPhos is crucial to achieving high enantioselectivity.
- Sun, Xianfeng,Zhou, Le,Wang, Chun-Jiang,Zhang, Xumu
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p. 2623 - 2626
(2008/02/13)
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- Enantiomeric products formed via different mechanisms: asymmetric hydrogenation of an α,β-unsaturated carboxylic acid involving a Ru(CH3COO)2[(R)-binap] catalyst
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Hydrogenation of (Z)-3-phenyl-2-butenoic acid with a Ru(CH3COO)2[(R)-binap] (BINAP=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) catalyst in methanol gives (S)-3-phenyl-2-butanoic acid and its R enantiomer in a 97:3 (4 atm) to 94:6 (100 atm) ratio in quantitative yield. Both hydrogen gas and protic methanol participate in the saturation of the olefinic bond. Analysis of the products obtained using (Z)-3-phenyl-2-butenoic acid-3-13C and either H2, a 1:1 H2-D2 mixture, or D2 in CH3OD indicates that several catalytic cycles are operative, showing different reactivity and stereoselectivity. The major S enantiomer was formed primarily by the standard Ru monohydride mechanism, whereas the minor R isomer is produced via more complicated routes.
- Yoshimura, Masahiro,Ishibashi, Yoshitaka,Miyata, Kengo,Bessho, Yuhki,Tsukamoto, Masaki,Kitamura, Masato
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p. 11399 - 11409
(2008/03/13)
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- Origin of the minor enantiomeric product in a noyori asymmetric hydrogenation: Evidence for pathways different to the major mechanism
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(Chemical Equation Presented) Hidden pathways: The enantiomeric products of the catalytic hydrogenation of an isotopically labeled substrate were separated. The ratios of the isotopomers revealed that the major and minor enantiomers are formed mostly through different mechanisms. Hence, when analyzing the energy profile of an asymmetric catalytic reaction with the Arrhenius equation, two competing diastereomorphic catalytic cycles should be considered (see scheme).
- Ishibashi, Yoshitaka,Bessho, Yuhki,Yoshimura, Masahiro,Tsukamoto, Masaki,Kitamura, Masato
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p. 7287 - 7290
(2007/10/03)
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