- Alkylidene Dihydropyridines Are Surrogates for Pyridylic Anions in the Conjugate Addition to α,β-Unsaturated Ketones
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We show that alkylidene dihydropyridines, readily prepared from 4-alkylpyridines, behave as soft nucleophiles toward a range of α,β-unsaturated ketones under the influence of silyl Lewis acids to give the products of conjugate addition. In contrast to existing methods, which use strongly basic pyridylic anions, this reaction tolerates a wide array of functional groups, providing access to useful heterocyclic scaffolds.
- Shi, Jiaqi,Sayyad, Ashik,Fishlock, Dan,Orellana, Arturo
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supporting information
p. 48 - 52
(2021/12/27)
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- Design, green synthesis, antioxidant activity screening, and evaluation of protective effect on cerebral ischemia reperfusion injury of novel monoenone monocarbonyl curcumin analogs
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Antioxidants with high efficacy and low toxicity have the potential to treat cerebral ischemia reperfusion injury (CIRI). Dienone monocarbonyl curcumin analogs (DMCA) capable of overcoming the instability and pharmacokinetic defects of curcumin possess notable antioxidant activity but are found to be significantly toxic. In this study, a novel skeleton of the monoenone monocarbonyl curcumin analogue sAc possessing reduced toxicity and improved stability was designed on the basis of the DMCA skeleton. Moreover, 32 sAc analogs were obtained by applying a green, simple, and economical synthetic method. Multiple sAc analogs with an antioxidant protective effect in PC12 cells were screened using an H2O2-induced oxidative stress damage model, and quantitative evaluation of structure–activity relationship (QSAR) model with regression coefficient of R2 = 0.918921 was built through random forest algorithm (RF). Among these compounds, the optimally active compound sAc15 elicited a potent protective effect on cell growth of PC12 cells by effectively eliminating ROS generation in response to oxidative stress injury by activating the Nrf2/HO-1 antioxidant signaling pathway. In addition, sAc15 exhibited good protection against CIRI in the mice middle cerebral artery occlusion (MCAO) model. In this paper, we provide a novel class of antioxidants and a potential compound for stroke treatment.
- He, Wenfei,Wang, Jingsong,Jin, Qiling,Zhang, Jiafeng,Liu, Yugang,Jin, Zewu,Wang, Hua,Hu, Linya,Zhu, Lu,Shen, Mengya,Huang, Lili,Huang, Shengwei,Li, Wulan,Zhuge, Qichuan,Wu, Jianzhang
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- Organocatalytic diastereo- And enantioselective oxa-hetero-Diels-Alder reactions of enones with aryl trifluoromethyl ketones for the synthesis of trifluoromethyl-substituted tetrahydropyrans
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Tetrahydropyran derivatives are found in bioactives, and introduction of the trifluoromethyl group into molecules often improves biofunctions. Here we report diastereo- and enantioselective oxa-hetero-Diels-Alder reactions catalyzed by amine-based catalyst systems that afford trifluoromethyl-substituted tetrahydropyranones. Catalyst systems and conditions suitable for the reactions to provide the desired diastereomer products with high enantioselectivities were identified, and various trifluoromethyl-substituted tetrahydropyranones were synthesized with high diastereo- and enantioselectivities. Mechanistic investigation suggested that the reactions involve a [4 + 2] cycloaddition pathway, in which the enamine of the enone acts as the diene and the ketone carbonyl group of the aryl trifluoromethyl ketone acts as the dienophile. In this study, tetrahydropyran derivatives with the desired stereochemistry that are difficult to synthesize by previously reported methods were concisely obtained, and the range of tetrahydropyran derivatives that can be synthesized was expanded. This journal is
- Pasha, Maira,Tanaka, Fujie
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supporting information
p. 9242 - 9250
(2021/11/16)
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- Iron-Catalyzed ?±,?-Dehydrogenation of Carbonyl Compounds
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An iron-catalyzed α,β-dehydrogenation of carbonyl compounds was developed. A broad spectrum of carbonyls or analogues, such as aldehyde, ketone, lactone, lactam, amine, and alcohol, could be converted to their α,β-unsaturated counterparts in a simple one-step reaction with high yields.
- Zhang, Xiao-Wei,Jiang, Guo-Qing,Lei, Shu-Hui,Shan, Xiang-Huan,Qu, Jian-Ping,Kang, Yan-Biao
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supporting information
p. 1611 - 1615
(2021/03/03)
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- 1,3-CYCLOHEXANEDIONE DERIVATIVES AND 1,3-CYCLOPENTANEDIONE DERIVATIVES AS BUFFERING MOLECULES IN NON-AQUEOUS SOLUTIONS
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This invention relates to 1,3-cyclohexanedione derivatives and 1,3-cyclopentanedione derivatives that have buffering function in non-aqueous solutions and to the use thereof for tuning the conditions to control chemical events in non-aqueous solutions. One aspect of the invention is a method for buffering a non-aqueous solution, including adding a buffering molecule to the non-aqueous solution, in which the non-aqueous solution contains an organic solvent, the buffering molecule is a 1,3-cyclohexanedione derivative or a 1,3-cyclopentanedione derivative, and the buffering molecule is optionally conjugated to a solid support.
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Paragraph 0069
(2021/04/23)
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- Catalytic Enantioselective Conjugate Addition of Stereodefined Di- and Trisubstituted Alkenylaluminum Compounds to Acyclic Enones
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Catalytic enantioselective conjugate addition (ECA) reactions with readily accessible and stereochemically defined E-, Z-, di- and trisubstituted alkenyl aluminum compounds are disclosed. Transformations are promoted by various NHC-copper catalysts (NHC=N-heterocyclic carbene), which are derived from enantiomerically pure sulfonate imidazolinium salts. The desired products were obtained in up to 89% yield and >99:1 e.r.; the alkenyl moiety was transferred with complete retention of its stereochemical identity in all instances. The scope and limitations of the approach, key mechanistic attributes, and representative functionalization are presented as well. (Figure presented.).
- McGrath, Kevin P.,Hubbell, Aran K.,Zhou, Yuebiao,Santos, Damián Padín,Torker, Sebastian,Romiti, Filippo,Hoveyda, Amir H.
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supporting information
p. 370 - 375
(2019/12/24)
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- One-pot two-step chemoenzymatic deracemization of allylic alcohols using laccases and alcohol dehydrogenases
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A series of enantioenriched (hetero)aromatic secondary allylic alcohols has been synthesized through deracemization of the corresponding racemic mixtures combining a non-selective chemoenzymatic oxidation (laccase from Trametes versicolor and oxy-radical TEMPO) and a stereoselective biocatalyzed reduction (lyophilized cells of E. coli overexpressing an alcohol dehydrogenase, ADH). Both steps were performed in aqueous medium under very mild reaction conditions. After optimization, a sequential one-pot two-step protocol was set up, obtaining the corresponding chiral alcohols in moderate to high conversions (48–95%) and enantiomeric excess (65->99% ee). Depending on the ADH stereopreference, both antipodes from these valuable chiral synthons could be prepared, even at preparative scale (119?178 mg), in a straightforward manner.
- Albarrán-Velo, Jesús,Gotor-Fernández, Vicente,Lavandera, Iván
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- Sequential Two-Step Stereoselective Amination of Allylic Alcohols through the Combination of Laccases and Amine Transaminases
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A sequential two-step chemoenzymatic methodology for the stereoselective synthesis of (3E)-4-(het)arylbut-3-en-2-amines in a highly selective manner and under mild reaction conditions is described. The approach consists of oxidation of the corresponding racemic alcohol precursors by the use of a catalytic system made up of the laccase from Trametes versicolor and the oxy-radical TEMPO, followed by the asymmetric reductive bio-transamination of the corresponding ketone intermediates. Optimisation of the oxidation reaction, exhaustive amine transaminase screening for the bio-transaminations and the compatibility of the two enzymatic reactions were studied in depth in search of a design of a compatible sequential cascade. This synthetic strategy was successful and the combinations of enzymes displayed a broad substrate scope, with 16 chiral amines being obtained in moderate to good isolated yields (29–75 %) and with excellent enantiomeric excess values (94 to >99 %). Interestingly, both amine enantiomers can be achieved, depending on the selectivity of the amine transaminase employed in the system.
- Albarrán-Velo, Jesús,Lavandera, Iván,Gotor-Fernández, Vicente
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p. 200 - 211
(2019/12/03)
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- Access to Spirocyclic Benzothiophenones with Multiple Stereocenters via an Organocatalytic Cascade Reaction
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The present report describes an organocatalytic cascade reaction between 2-alkylidene benzo[b]thiophenone derivatives and enones in the presence of the Cinchona alkaloid amine. Spirobenzothiophenonic cyclohexane derivatives containing three stereocenters were prepared via one-step synthesis in yields ranging from 88 to 96% and in enantioselectivities (enantiomeric excess (ee)) ranging from 85 to 97%, with diastereoselectivities of approximately 14/2/1. Therefore, this method provides an efficient route for the synthesis of a new class of optically active 2-spirobenzothiophenones.
- Formánek, Bed?ich,Tauchman, Ji?í,Císa?ová, Ivana,Vesely, Jan
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p. 8510 - 8521
(2020/07/16)
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- A bioinspired microreactor with interfacial regulation for maximizing selectivity in a catalytic reaction
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We report a bioinspired emulsion microreactor composed of an electrical double layer to mimic the functions of cell membranes. This "artificial cell"can modulate the phase-oriented transport of reagents at the oil-liquid interface via the electrical double layer, affording a powerful tool to optimize the selectivity in a catalytic reaction. This journal is
- Han, Chenhui,Li, Xin-Hao,Waclawik, Eric R.,Xu, Haolan,Xu, Jingsan
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supporting information
p. 8059 - 8062
(2020/09/09)
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- Boosting multiple photo-assisted and temperature controlled reactions with a single redox-switchable catalyst: Solvents as internal substrates and reducing agent
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An alternative and economically viable process for the synthesis of β-aryl enals, enones and the aryl amines has been developed by partial oxidation of ethanol, isopropanol and N, N-dimethyl formamide (DMF). The formation of β-aryl enals, enones and the aryl amines was catalyzed by a mixed metal oxides layer of cobalt and chromium supported on halloysite nanotubes, designated as CoCr2O4-HNT. The C[sbnd]C and C[sbnd]N bond formation reactions were found to be influenced by temperature and the nature of base. The condensation of aldehyde with in situ generated acetaldehyde by ethanol oxidation forming β-aryl enals occurred selectively at 120 °C. The partial oxidation of isopropanol to acetone and its condensation with aldehydes forming β-aryl enones occurred at room temperature. Increase in temperature caused the liberation of hydrogen gas from isopropanol and allowed the reversible reduction of aldehydes to alcohols. Increase in temperature in isopropanol and increase in base concentration in ethanol causes the selective reduction of aldehydes to alcohols. Besides being active for the Claisen-Schmidt type of reactions and the aryl halides amination process, the synthesized catalyst was also found to be highly active for the photocatalytic oxidation of benzyl alcohols in absence of any external oxidizing agent. The positive holes (h+) generated at the Co(II) site as evident from EPR analysis was considered to be responsible for high photocatalytic activity of the material reducing the recombination rate of holes and electrons (e?). Density Functional Theory calculations were performed to understand the mechanism of ethanol oxidation to acetaldehyde.
- Bania, Kusum K.,Baruah, Manash J.,Bhattacharyya, Pradip K.,Das, Biraj,Karunakar, Galla V.,Roy, Subhasish,Saikia, Lakshi,Saikia, Pinku,Sharma, Mukesh
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p. 104 - 121
(2020/06/01)
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- Iodine/water-mediated deprotective oxidation of allylic ethers to access α,β-unsaturated ketones and aldehydes
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The first iodine/water-mediated deprotective oxidation of allylic ethers to access α,β-unsaturated ketones and aldehydes was achieved. The reaction tolerates a wide range of functionalities. Furthermore, this protocol was found to be applicable to the oxidative transformation of allylic acetates. The proposed mechanism involves an oxygen transfer from solvent water to the carbonyl products.
- Chen, Weifeng,Jiang, Kezhi,Xue, Yuntian,Yan, Yaolong,Yang, Lei
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p. 14720 - 14724
(2020/04/27)
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- RhIII-Catalyzed Synthesis of Highly Substituted 2-Pyridones using Fluorinated Diazomalonate
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A RhIII-catalyzed strategy was developed for the rapid construction of highly substituted 2-pyridone scaffolds using α,β-unsaturated oximes and fluorinated diazomalonate. The reaction proceeds through direct, site-selective alkylation based on migratory insertion and subsequent cyclocondensation. A wide substrate scope with different functional groups was explored. The requirement of fluorinated diazomalonate was explored for this transformation. The developed methodology was further extended with the synthesis of the bioactive compound.
- Das, Debapratim,Sahoo, Gopal,Biswas, Aniruddha,Samanta, Rajarshi
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supporting information
p. 360 - 364
(2020/01/25)
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- First aromatic amine organocatalysed activation of α,β-unsaturated ketones
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This work provides an unprecedented example of a chiral aromatic amine used to activate α,β-unsaturated ketones in asymmetric aminocatalysis. Chiral aromatic diamine VII has been efficiently employed, as a proof of concept, in the Michael addition reaction between benzylideneacetones (1a-f) and coumarins (2a-d). The reaction gives rise to warfarin derivatives 3 with promising results using this family of catalysts for the first time. The additional studies performed supported the bifunctional mode of activation of the chiral catalyst VII and the covalent nature of the interactions between the catalyst VII and benzylideneacetones 1.
- Sonsona, Isaac G.,Marqués-López, Eugenia,Gimeno, M. Concepción,Herrera, Raquel P.
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supporting information
p. 12233 - 12240
(2019/08/12)
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- An access to α, β-unsaturated ketones via dual cooperative catalysis
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A dual cooperative organocatalytic approach for the synthesis of α, β-unsaturated ketones is described. This one pot transformation is realized via a domino Knoevenagel-Michael-retro Michael reaction sequence. Various aliphatic ketones reacted smoothly with aromatic as well as aliphatic aldehydes in presence catalytic amount of Meldrum's acid and bifunctional amine. The highlights of this protocol are the easy availability of catalysts, high selectivity, and functional group tolerance. The reaction proved to highly E-selective with no side products emanating from self-condensation, unlike the base-mediated reactions.
- Syamala, Lakshmi V.R. Babu,Khopade, Tushar M.,Warghude, Prakash K.,Bhat, Ramakrishna G.
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supporting information
p. 88 - 91
(2018/12/05)
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- Preparation method for impurity of parecoxib sodium
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The invention belongs to the technical field of medicinal chemistry, and in particular relates to a preparation method for an impurity of parecoxib sodium. A synthetic method of the compound PRN073-11is never mentioned in the prior art, a very small amoun
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Paragraph 0063-0067
(2019/10/02)
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- Use of a switchable-hydrophilicity solvent as both a solvent and a catalyst in aldol condensation
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A switchable-hydrophilicity solvent, N,N-dimethylcyclohexylamine, was used as a recyclable catalyst and solvent for aldol condensation, giving >97% pure product in 94% isolated yield without the need for purification or additional solvents. CO2-triggered separation produced yields greater than conventional workup and allowed facile recycling of the amine.
- Poole, Hailey,Gauthier, Jeremy,Vanderveen, Jesse R.,Jessop, Philip G.,Lee, Roland
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supporting information
p. 6263 - 6267
(2019/12/03)
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- Construction of Multiple-Substituted Chiral Cyclohexanes through Hydrogenative Desymmetrization of 2,2,5-Trisubstituted 1,3-Cyclohexanediones
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The construction of chiral multiple-substituted cyclohexanes motifs is a challenging topic in organic synthesis. By the combination of desymmetrization and remote stereocontrol, a ruthenium-catalyzed transfer hydrogenative desymmetrization of 2,2,5-trisubstituted 1,3-cyclohexanediones has been successfully developed for the construction of chiral multiple-substituted cyclohexanes with high enantioselectivity and diastereoselectivity. When an ester group was introduced to the two-position, a hydrogenative desymmetrization/transesterification cascade occurred, affording the bicyclic lactones bearing three stereocenters, including two discrete stereocenters and one quaternary stereogenic center, with high enantioselectivity. The products are the multiple-substituted chiral cyclohexanes bearing the hydroxyl and carbonyl functional groups, which provide a new opportunity for further precise elaboration.
- Yu, Chang-Bin,Song, Bo,Chen, Mu-Wang,Shen, Hong-Qiang,Zhou, Yong-Gui
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supporting information
p. 9401 - 9404
(2019/11/28)
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- Discovery of novel 5-methyl-1H-pyrazole derivatives as potential antiprostate cancer agents: Design, synthesis, molecular modeling, and biological evaluation
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Androgen receptor (AR) signaling functions as a core driving force for the progression of prostate cancer (PCa), and AR has been proved to be an effective therapeutic target even for castration-resistant prostate cancer (CRPC). Herein, structural modification via a fragments splicing strategy was performed based on two lead compounds T3 and 10e, leading to the discovery of a series of 5-methyl-1H-pyrazole derivatives. AR reporter gene assay revealed compounds A13 and A14 as potent AR antagonists. Some of the compounds in this series inhibited growth of PCa LNCaP cells more efficiently than enzalutamide. A13 and A14 also showed improved metabolic stability compared with 10e in human liver microsomes.
- Zhang, Daoguang,Asnake, Solomon,Zhang, Jingya,Olsson, Per-Erik,Zhao, Guisen
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p. 1113 - 1124
(2018/03/05)
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- 5-methyl-1H-pyrazole derivative, preparation method and applications thereof
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The invention discloses a 5-methyl-1H-pyrazole derivative, a preparation method and applications thereof, wherein the compound has a structure represented by a general formula (I). The invention further provides the preparation method and the applications
- -
-
Paragraph 0057-0058; 0059
(2018/05/01)
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- Rh(III)-Catalyzed Enaminone-Directed Alkenyl C-H Activation for the Synthesis of Salicylaldehydes
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A Rh(III)-catalyzed enaminone-directed alkenyl C-H coupling with alkynes for the synthesis of salicylaldehyde derivatives is reported. This represents a unique example of benzene ring framework formation through a transition-metal-catalyzed, directed C-H activation strategy. The two incorporated reactive functionalities, aldehyde and hydroxy groups, provide convenient synthetic handles for further structural elaboration.
- Qi, Bing,Guo, Shan,Zhang, Wenjing,Yu, Xiaolong,Song, Chao,Zhu, Jin
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supporting information
p. 3996 - 3999
(2018/07/15)
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- Mild Chemoenzymatic Oxidation of Allylic sec-Alcohols. Application to Biocatalytic Stereoselective Redox Isomerizations
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The design of catalytic oxidative methodologies in aqueous medium under mild reaction conditions and using molecular oxygen as final electron acceptor represents a suitable alternative to the traditional oxidative transformations. These methods are especially relevant if other functionalities that can be oxidized are present within the same molecule, as in the case of allylic alcohols. Herein we apply a simple chemoenzymatic system composed of the laccase from Trametes versicolor and 2,2,6,6-tetramethylpiperidinyloxy radical (TEMPO) to oxidize a series of racemic allylic sec-alcohols into the corresponding α,β-unsaturated ketones. Afterward, these compounds react with different commercially available ene-reductases to afford the corresponding saturated ketones. Remarkably, in the case of trisubstituted alkenes, the bioreduction reaction occurred with high stereoselectivity. Overall, a bienzymatic one-pot two-step sequential strategy has been described with respect to the synthesis of saturated ketones starting from racemic allylic alcohols, thus resembling the metal-catalyzed redox isomerizations of these derivatives that have been previously reported in the literature.
- Martínez-Montero, Lía,Gotor, Vicente,Gotor-Fernández, Vicente,Lavandera, Iván
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p. 2413 - 2419
(2018/03/13)
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- Catalytic Asymmetric Conjugate Addition of Indolizines to α,β-Unsaturated Ketones
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A catalytic enantioselective conjugate addition of indolizines to enones is described. The chiral phosphoric acid (S)-TRIP activates α,β-unsaturated ketones, thereby promoting an enantioface-differentiating attack by indolizines. Using this reaction, several alkylated indolizines were synthesized in good yields and with enantiomeric ratios of up to 98:2.
- Correia, José Tiago Menezes,List, Benjamin,Coelho, Fernando
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supporting information
p. 7967 - 7970
(2017/06/27)
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- Palladium-Catalyzed Cleavage of α-Allenylic Aryl Ether toward Pyrazolemethylene-Substituted Phosphinyl Allenes and Their Transformations via Alkenyl C-P(O) Cleavage
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A palladium-catalyzed two-component coupling of allenylphosphine oxides with conjugated N-tosylhydrazones is revealed. For the first time, the cleavage of α-allenylic aryl ether toward pyrazolemethylene-substituted phosphinyl allenes enabled facile synthesis of combined motifs with pyrazole and allene. Moreover, the obtained adducts could be easily transformed to potential bioactive multifunctionalized phosphinates via a novel alkenyl C-P(O) cleavage.
- Zhu, Jie,Mao, Mao,Ji, Huan-Jing,Xu, Jiang-Yan,Wu, Lei
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supporting information
p. 1946 - 1949
(2017/04/28)
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- Iridium-catalysed desilylative acylation of 1-alkenylsilanes
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We report the iridium-catalysed desilylative acylation of styryl and dienyl silanes by acid anhydrides to afford (E)-α,β-unsaturated ketones. The [{Ir(μ-Cl)(cod)}2] catalyst is the first non-rhodium complex successfully applied for this type of
- Zaranek, Maciej,Skrodzki, Maciej,Szudkowska-Fr?tczak, Justyna,Dodot, Maciej,Kownacki, Ireneusz,Orwat, Bartosz,Pawlu?, Piotr
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- Kinetic and Mechanistic Examination of Acid-Base Bifunctional Aminosilica Catalysts in Aldol and Nitroaldol Condensations
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The kinetic and mechanistic understanding of cooperatively catalyzed aldol and nitroaldol condensations is probed using a series of mesoporous silicas functionalized with aminosilanes to provide bifunctional acid-base character. Mechanistically, a Hammett analysis is performed to determine the effects of electron-donating and electron-withdrawing groups of para-substituted benzaldehyde derivatives on the catalytic activity of each condensation reaction. This information is also used to discuss the validity of previously proposed catalytic mechanisms and to propose a revised mechanism with plausible reaction intermediates. For both reactions, electron-withdrawing groups increase the observed rates of reaction, though resonance effects play an important, yet subtle, role in the nitroaldol condensation, in which a p-methoxy electron-donating group is also able to stabilize the proposed carbocation intermediate. Additionally, activation energies and pre-exponential factors are calculated via the Arrhenius analysis of two catalysts with similar amine loadings: one catalyst had silanols available for cooperative interactions (acid-base catalysis), while the other was treated with a silanol-capping reagent to prevent such cooperativity (base-only catalysis). The values obtained for activation energies and pre-exponential factors in each reaction are discussed in the context of the proposed mechanisms and the importance of cooperative interactions in each reaction. The catalytic activity decreases for all reactions when the silanols are capped with trimethylsilyl groups, and higher temperatures are required to make accurate rate measurements, emphasizing the vital role the weakly acidic silanols play in the catalytic cycles. The results indicate that loss of acid sites is more detrimental to the catalytic activity of the aldol condensation than the nitroaldol condensation, as evidenced by the significant decrease in the pre-exponential factor for the aldol condensation when silanols are unavailable for cooperative interactions. Cooperative catalysis is evidenced by significant changes in the pre-exponential factor, rather than the activation energy for the aldol condensation.
- Collier, Virginia E.,Ellebracht, Nathan C.,Lindy, George I.,Moschetta, Eric G.,Jones, Christopher W.
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p. 460 - 468
(2016/01/12)
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- Enzyme-catalyzed domino reaction: Efficient construction of spirocyclic oxindole skeleton using porcine pepsin
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Pepsin from porcine gastric mucosa was used as a sustainable and environmentally friendly biocatalyst in the domino Knoevenagel/Michael/Michael reaction for the synthesis of spirooxindole derivatives in methanol. A wide range of isatins and α,β-unsaturated ketones reacting with malononitrile provided the corresponding products in yields of up to 99% with diastereoselectivities of up to >99:1 dr. This pepsin-catalyzed domino reaction provided a novel case of enzyme catalytic promiscuity.
- He, Yan-Hong,He, Tao,Guo, Jun-Tao,Li, Rui,Xiang, Yang,Yang, Da-Cheng,Guan, Zhi
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p. 2239 - 2248
(2016/04/26)
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- Synthesis and neuroprotective evaluation of (E)-3,4-dihydroxystyryl p-substituted-phenethyl ketone derivatives against inflammatory and oxidative injury
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(E)-3,4-dihydroxystyryl p-substituted-phenethyl ketones and their 3,4-diacetylated derivatives were synthesized and examined their neuroprotective activities to further study the effect of p-substituents on the aromatic ring. The results revealed that steric hindrance effect of p-substituents has impact on neuroprotective activities against inflammatory and oxidative injury. Introduction of the bulkier groups are more beneficial to improve the neuroprotective activities than smaller groups. Compounds (4–5h, 4–5i and 4–5e) with p-substituted trifluoromethyl, isopropyl and t-butyl groups exhibited the best effects among all the target compounds.
- Cheng, Can,Ning, Xianling,Luo, Yongming,Tian, Chao,Wang, Xiaowei,Guo, Ying,Liu, Junyi,Zhang, Zhili
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p. 1678 - 1685
(2016/07/30)
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- Organocatalyzed Asymmetric Conjugate Addition of Heteroaryl and Aryl Trifluoroborates: A Synthetic Strategy for Discoipyrrole D
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Bis-heteroaryl or bis-aryl stereocenters were formed by an organocatalytic enantioselective conjugate addition using the respective trifluoroborate salts as nucleophiles. Control studies suggested that fluoride dissociation is necessary in the anhydrous conditions. This strategy is applicable to the synthesis of discoipyrrole D, an inhibitor of BR5 fibroblast migration.
- Shih, Jiun-Le,Nguyen, Thien S.,May, Jeremy A.
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supporting information
p. 9931 - 9935
(2015/08/19)
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- Polyethyleneimine-Supported Triphenylphosphine and Its Use as a Highly Loaded Bifunctional Polymeric Reagent in Chromatography-Free One-Pot Wittig Reactions
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A polyethyleneimine-supported triphenylphosphine reagent has been synthesized and used as a highly loaded bifunctional homogeneous reagent in a range of one-pot Wittig reactions that afforded high yields of the desired products after simple purification procedures. The approach also served efficiently in tandem reaction sequences involving a one-pot Wittig reaction followed by conjugate reduction of the newly formed alkene product in situ. In these transformations, the phosphine oxide groups generated in the Wittig reaction served as the catalyst for activating trichlorosilane in the subsequent reduction reaction.
- Xia, Xuanshu,Toy, Patrick H.
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supporting information
p. 1737 - 1743
(2015/07/20)
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- Design, synthesis and biological evaluation of novel C3-functionalized oxindoles as potential Pim-1 kinase inhibitors
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A novel series of C3-functionalized oxindoles, 3-(2-oxo-4-phenylbut-3-en-1-ylidene)indolin-2-ones, were designed, synthesized and investigated for inhibition of cell proliferation against different types of human cancer cell lines, including SW620, HeLa and A549. This biological study showed that these compounds containing the scaffolds of indole and aromatic α,β-unsaturated ketone had moderate to significant antitumor activities. Further study suggested that compound 4b, as one of this kind of structure derivative, showed broad-spectrum antitumor activities against MCF-7, PC-3, SKOV-3, U87, SMMC-7721, SY5Y and A875 cancer cell lines. Besides, the results of the inhibition of Pim kinases indicated that compound 4b showed selective and efficient anti-Pim-1 kinase activity (IC50 = 5 μM). Docking simulation, flow cytometry (FCM), and Hoechst 33342 staining assay suggested that the most active compound 4b induced cell death through apoptosis via binding to the active ATP pocket of Pim-1. Moreover, it showed that compound 4b had strong inhibition of tubulin polymerization which may be caused by inhibiting Pim-1. This journal is
- Sun, Hong-Bao,Wang, Xiao-Yan,Li, Guo-Bo,Zhang, Li-Dan,Liu, Jie,Zhao, Li-Feng
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p. 29456 - 29466
(2015/04/14)
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- Synthesis of new 4-phenylpyrimidine-2(1H)-thiones and their potency to inhibit COX-1 and COX-2
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Several new 4-phenylpyrimidine-2(1H)-thiones have been prepared and investigated for their potencies to inhibit COX-1 and COX-2 enzymes, and COX-2 expression in THP-1 cells. Structure-activity-relationships and physicochemical parameters are discussed. Pharmacophore screening and docking studies were carried out for the most active compound.
- Seebacher, Werner,Faist, Johanna,Presser, Armin,Weis, Robert,Saf, Robert,Kaserer, Teresa,Temml, Veronika,Schuster, Daniela,Ortmann, Sabine,Otto, Nadine,Bauer, Rudolf
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p. 552 - 559
(2015/07/27)
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- A multicomponent pathway-inspired regioselective synthesis of 2,3,4-trisubstituted 1H-pyrroles via [3+2] cycloaddition reaction
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A copper catalyzed regioselective synthesis of 2,3,4-trisubstituted 1H-pyrroles using a novel three-component coupled domino reaction of aldehydes, ketones and alkyl isocyanoacetates is reported. This transformation proceeds through the formation of a chalcone followed by a [3+2] cycloaddition reaction to obtain α-cuprioisocyanide, a cyclic organocopper intermediate, which on copper-hydrogen exchange followed by oxidation exclusively offers 2,3,4-trisubstituted 1H-pyrrole.
- Kalmode, Hanuman P.,Vadagaonkar, Kamlesh S.,Murugan, Kaliyappan,Chaskar, Atul C.
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p. 4631 - 4639
(2015/06/16)
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- Synthesis of α-Tertiary Amine Derivatives by Intermolecular Hydroamination of Unfunctionalized Alkenes with Sulfamates under Trifluoromethanesulfonic Acid Catalysis
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An efficient and mild trifluoromethanesulfonic acid-catalyzed hydroamination of unfunctionalized alkenes to afford α-tertiary amine derivatives at temperatures as low as room temperature is reported. 2,2,2-Trifluoroethyl sulfamate was found to be the optimal nitrogen source because its good solubility in both organic solvents and water facilitated both conversion and purification. The reaction conditions were compatible with a variety of substrate functional groups and afforded moderate to good yields. The desired amine compounds could be obtained easily by means of a mild, one-pot, redox-neutral deprotection procedure. Caryolane amine was synthesized with excellent chemo- and regioselectivities by means of a cascade hydroamination reaction of β-caryophyllene.
- Fei, Jun,Wang, Zhen,Cai, Zheren,Sun, Hao,Cheng, Xu
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supporting information
p. 4063 - 4068
(2016/01/25)
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- Iridium(I)-catalyzed regioselective C-H activation and hydrogen-isotope exchange of non-aromatic unsaturated functionality
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Isotopic labelling is a key technology of increasing importance for the investigation of new C-H activation and functionalization techniques, as well as in the construction of labelled molecules for use within both organic synthesis and drug discovery. Herein, we report for the first time selective iridium-catalyzed C-H activation and hydrogen-isotope exchange at the β-position of unsaturated organic compounds. The use of our highly active [Ir(cod)(IMes)(PPh3)][PF6] (cod = 1, 5-cyclooctadiene) catalyst, under mild reaction conditions, allows the regioselective β-activation and labelling of a range of α, β-unsaturated compounds with differing steric and electronic properties. This new process delivers high levels of isotope incorporation over short reaction times by using low levels of catalyst loading.
- Kerr, William J.,Mudd, Richard J.,Paterson, Laura C.,Brown, Jack A.
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supporting information
p. 14604 - 14607
(2015/03/04)
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- Facile synthesis of Z -alkenes via uphill catalysis
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Catalytic access to thermodynamically less stable Z-alkenes has recently received considerable attention. These approaches have relied upon kinetic control of the reaction to arrive at the thermodynamically less stable geometrical isomer. Herein, we present an orthogonal approach which proceeds via photochemically catalyzed isomerization of the thermodynamic E-alkene to the less stable Z-isomer which occurs via a photochemical pumping mechanism. We consider two potential mechanisms. Importantly, the reaction conditions are mild, tolerant, and operationally simple and will be easily implemented.
- Singh, Kamaljeet,Staig, Shannon J.,Weaver, Jimmie D.
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supporting information
p. 5275 - 5278
(2014/05/06)
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- Oxygen as single oxidant for two steps: Base-free one-pot Pd(ii)-catalyzed alcohol oxidation & arylation to halogen-intact β-aryl α,β-enones
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Using oxygen as the sole oxidant for two steps, we developed a new method to synthesize β-aryl α,β-enones by fine-tuning the Pd(ii)-catalyzed oxidation of allyl alcohol to subsequent arylation with arylboronic acids, arylboronic ester and aryltrifluoroborate salt. This one-pot green method does not require copper salt, base, and intermediate isolation. Halogen-bearing chalcones, dibenzylideneacetones and arylalkyl enones were synthesized in good yields. This journal is
- Vellakkaran, Mari,Andappan, Murugaiah M. S.,Nagaiah, Kommu
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p. 45490 - 45494
(2014/12/10)
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- Graphene based material as a base catalyst for solvent free Aldol condensation and Knoevenagel reaction at room temperature
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Graphene oxide (GO) acts as a highly active heterogeneous base catalyst for a wide variety of reactions. Here we have described the catalytic activities of GO in the condensation reaction of various substituted benzaldehydes with acetophenone (aldol condensation) and with active methylene compound malononitrile (Knoevenagel reaction) at room temperature under solvent free condition. GO is characterized by powder X-ray diffraction (XRD), UV-visible spectra, Fourier transform infrared spectroscopy (FT-IR) and AFM. The experimental results showed that the GO had higher catalytic activity and it can be recycled without significant loss of its activity.
- Islam, Sk Manirul,Roy, Anupam Singha,Dey, Ram Chandra,Paul, Sumantra
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- Carbon quantum dots with photoenhanced hydrogen-bond catalytic activity in aldol condensations
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Carbon quantum dots (CQDs) were synthesized by an electrochemical etching method. The CQDs are well-dispersed with uniform size about 5 nm. FT-IR spectra suggest the presence of many hydroxyl groups on the surface of CQDs. Here, CQDs with diameter approximately 5 nm, directly used as effective heterogeneous nanocatalysts for H-bond catalysis in aldol condensations, show excellent photoenhanced catalytic ability (89% yields when 4-cyanobenzaldehyde is used). It demonstrated that aldol condensation between acetone and aromatic aldehydes resulted in higher yields with visible light irradiation than in the dark, confirming visible light is necessary for good conversion. The H-bond catalytic activities of CQDs can be significantly enhanced with visible light irradiation. The high catalytic activities of CQDs are due to highly efficient electron-accepting capabilities. Repeated catalytic experiments suggest that the CQD catalyst can be easily recycled as a heterogeneous catalyst with a long catalyst life.
- Han, Yuzhi,Huang, Hui,Zhang, Hengchao,Liu, Yang,Han, Xiao,Liu, Ruihua,Li, Haitao,Kang, Zhenhui
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p. 781 - 787
(2014/04/03)
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- Enviornmentally benign michael and claisen schmidt reaction of aromatic carbonyl compounds by alkaline polyionic resin
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A regioselective Michael reaction between aryl methyl ketones and α,β-unsaturated compounds has been carried out using basic polyionic resin as a reusable reagent. Results indicate that the reaction proceeds in consecutive manner as double Michael (27-65%) and triple Michael (40-45%) products with overall yields of 55-80%. Moreover, A-2XMP resin has also been applied on Claisen Schmidt condensations of aromatic aldehydes and ketones (acyclic as well as cyclic) under different reaction conditions yielding dehydrated products in 82-94% yield. The reactions give an opportunity for easy separation, reusability of polyionic resin and easy purification of products in continuous or multiple processing of organic compounds.
- Jaitak, Vikas,Kaul,Das, Pralay
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p. 1137 - 1145
(2013/09/24)
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- Palladium-catalyzed conjugate addition of arylsulfonyl hydrazides to α,β-unsaturated ketones
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A palladium-catalyzed desulfitative-denitrogenative conjugate addition of arylsulfonyl hydrazides to α,β-unsaturated ketones is described. The reaction showed very good selectivity and tolerated a wide range of functionalities under an atmosphere of oxygen with or without the aid of a metal co-oxidant. The Royal Society of Chemistry 2013.
- Chen, Wen,Chen, Hui,Xiao, Fuhong,Deng, Guo-Jun
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supporting information
p. 4295 - 4298
(2013/08/23)
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- Effect of phosphorus amount on the particle size and catalytic performance of heterogeneous nickel(ii) schiff-base complex in aldol condensation reaction
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The organic-inorganic hybrid of citric acid, tetraethoxysilane (TEOS), and triethylphosphate (TEP) doped by a nickel Schiff-base complex was prepared by sol-gel method. The prepared composites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmittance electron microscopy (TEM), scanning tunnelling microscopy (STM), and infrared spectroscopy (IR). In order to determine the phosphorus amount effect on the catalytic activity of the prepared composites, the aldol condensation was used as a model reaction. The results revealed that the composite with 10% phosphorus is a better catalyst in comparison with other composites.
- Eshtiagh-Hosseini, Hossein,Tabari, Taymaz
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p. 1778 - 1791
(2013/11/06)
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- Enantioselective [4 + 2] cycloaddition of cyclic N-sulfimines and acyclic enones or ynones: A concise route to sulfamidate-fused 2,6-disubstituted piperidin-4-ones
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A concise route to valuable sulfamate-fused 2,6-disubstituted piperidin-4-ones or 2,3-dihydropyridin-4(1H)-ones in good yield with high diastereo- and enantioselectivity is presented. The combination of chiral primary amine and o-fluorobenzoic acid efficiently promoted an asymmetric [4 + 2] cycloaddition reaction of N-sulfonylimines and enones or ynones. The cycloaddition reaction between cyclic N-sulfonylimines and ynones is first reported.
- Liu, Yong,Kang, Tai-Ran,Liu, Quan-Zhong,Chen, Lian-Mei,Wang, Ya-Chuan,Liu, Jie,Xie, Yong-Mei,Yang, Jin-Liang,He, Long
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p. 6090 - 6093
(2014/01/06)
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- Synthesis of β-fluoroenones and their reductive rearrangement in aqueous media
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In this paper, a simple and efficient preparation of β-fluoroenones, as a mixture of E/Z isomers with the E-isomer as the main product, from 1,2-allenic ketones by using TBAF·3H2O in water as a nucleophilic fluorination agent has been developed. Moreover, in exploring the synthetic applications of β-fluoroenones, an unprecedented reductive defluorination rearrangement of β-fluoroenones toward enones under mild conditions in aqueous media was also discovered.
- He, Yan,Shen, Nana,Fan, Xuesen,Zhang, Xinying
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p. 8818 - 8823
(2013/09/23)
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- Multimetallic Ir-Sn3-catalyzed substitution reaction of π-activated alcohols with carbon and heteroatom nucleophiles
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An atom economic and catalytic substitution reaction of π-activated alcohols by a multimetallic IreSn3 complex has been demonstrated. The multimetallic IreSn3 complex can be easily synthesized from the reaction between [Cp*IrCl2]2 and SnCl2. In presence of as little as 1 mol % of the catalyst three different types of π-activated alcohols, namely benzyl, allyl, and propargyl alcohols, have been successfully transformed into alkylated products using carbon (arenes, heteroarenes, allyltrimethylsilane, and 1,3-dicarbonyls), nitrogen (sulfonamides), oxygen (alcohols), and sulfur (thiols) nucleophiles in very high yields. An electrophilic mechanism is proposed from the Hammett correlation study.
- Maity, Arnab Kumar,Chatterjee, Paresh Nath,Roy, Sujit
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p. 942 - 956
(2013/07/25)
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- Terminal olefins to linear α,β-unsaturated ketones: Pd(II)/hypervalent iodine co-catalyzed wacker oxidation-dehydrogenation
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Development of a mild (35 C, no Bronsted acids) tandem Wacker oxidation-dehydrogenation of terminal olefins was accomplished using palladium(II) and hypervalent iodine co-catalysis. The reaction affords linear aryl and alkyl α,β-unsaturated ketones directly from readily available terminal olefins in good yields (average 75% per step) with excellent functional group tolerance and chemo- and stereoselectivities. The hypervalent iodine co-catalyst was found to be critical for dehydrogenation but was not effective as a stoichiometric oxidant.
- Bigi, Marinus A.,White, M. Christina
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p. 7831 - 7834
(2013/07/19)
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- Highly enantioselective biomimetic intramolecular dehydration: Kinetic resolution of β-hydroxy ketones catalyzed by β-turn tetrapeptides
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Racemic β-hydroxy ketones were kinetically resoluted into the enantiopure isomers and (E)-α,β-unsaturated ketones using catalytic asymmetric intramolecular dehydration for the first time. Synthetic tetrapeptides were used to imitate fatty acid dehydratase
- Du, Zhi-Xue,Zhang, Li-Yuan,Fan, Xin-Yuan,Wu, Feng-Chun,Da, Chao-Shan
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supporting information
p. 2828 - 2832
(2013/06/05)
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- Enantioselective formal aza-Diels-Alder reactions of enones with cyclic imines catalyzed by primary aminothioureas
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A highly enantio- and diastereoselective synthesis of indolo- and benzoquinolizidine compounds has been developed through the formal aza-Diels-Alder reaction of enones with cyclic imines. This transformation is catalyzed by a new bifunctional primary aminothiourea that achieves simultaneous activation of both the enone and imine reaction components.
- Lalonde, Mathieu P.,McGowan, Meredeth A.,Rajapaksa, Naomi S.,Jacobsen, Eric N.
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supporting information
p. 1891 - 1894
(2013/04/10)
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- FLAVONE DERIVATIVES AND THEIR PREPARATIVE METHOD AND MEDICAL USE
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Flavone derivatives, preparative method of the derivatives and use thereof as medicaments for treating diabetes. The structure of the derivatives is presented by formula 1: In the structure, R1 and R2, which are identical or not, represent hydrogen atom, halogen, cyano, hydroxyl, trifluoromethyl, thio-methyl, benzyloxy, C1-C8 linear chain or branch chain alkyl, C1-C8 linear chain or branch chain alkoxy. The pharmacological test indicates that the flavone derivatives can significantly increase the glucose consumption of Hep-G2 cell with insulin resistance activity, promote translocation of glucose transporter 4 of skeletal muscle cells (L6GLUT4myc) at different level, and significantly increase glucose intake and utilization by cells. The test proves the fact for the first time that the flavone derivatives can significantly promote translocation of glucose transporter 4 of skeletal muscle cells, and one of the mechanisms for treating diabetes is activating the cell AMPK phosphorylation and phosphorylating the downstream ACC.
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Paragraph 0028
(2013/09/12)
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- Design, synthesis and biological evaluation of hybrid molecules containing conjugated styryl ketone and α-bromoacryloyl moieties
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There was a major interest in the last years in the design of anticancer agents containing the 1,5-diaryl-3-oxo-1,4-pentadienyl system. The modification of this pharmacophore by the introduction of an additional Michael acceptor represents a strategy to obtain novel potential antiproliferative agents. In a continuing study of hybrid compounds containing the α-bromoacryloyl moiety as potential anticancer drugs, we synthesized two novel series of hybrids 3a-i and 4a-i, in which this moiety was linked to the 1,5-diaryl-1,4-pentadien-3-one system. Many of the conjugates prepared (3b, 3c and 3g) demonstrated pronounced antiproliferative activity against five cancer cell lines, being more active than the reference compound Melphalan. Compounds 3e and 4b were also examined for their effects on the cell cycle progression of K562 cells. The detection of a sub-G1 peak upon incubation with these compounds suggested that 3e and 4b also exert their growth inhibiting effects by induction of apoptosis.
- Romagnoli, Romeo,Baraldi, Pier Giovanni,Cruz-Lopez, Olga,Salvador, Maria Kimatrai,Preti, Delia,Tabrizi, Mojgan Aghazadeh,Balzarini, Jan,Canella, Alessandro,Fabbri, Enrica,Gambari, Roberto
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experimental part
p. 140 - 152
(2012/07/17)
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