- A short route to access oxaspiro[: N,3,3]propellanes
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Novel access to oxaspiro[n,3,3]propellanes has been developed from bicyclic lactones directly prepared by a photochemical hydroxymethylation or alternatively by a three-step sequence. Thanks to the presence of additional hydroxy- and propargylic groups, a second cyclization catalyzed by silver or bismuth salts, led to the propellane structure which was finally transformed into spiranic derivatives by a Simmons-Smith reaction or condensation with α-ketoesters.
- Nassar, Youssef,Piva, Olivier
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Read Online
- Electrochemical two-electron oxygen reduction reaction (ORR) induced aerobic oxidation of α-diazoesters
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Electrochemical oxygen reduction reaction (ORR) is a powerful tool for introducing oxygen functional groups in synthetic chemistry. However, compared with the well-developed one-electron oxygen reduction process, the applications of two-electron oxygen re
- Chen, Liang,Gao, Meng,Lu, Cuifen,Ma, Chao,Ruan, Mengyao,Wen, Ziyang,Yang, Fan,Yang, Guichun
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p. 2168 - 2171
(2022/02/17)
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- Unraveling two pathways for NHPI-mediated electrocatalytic oxidation reaction
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Two pathways for N-hydroxyphthalimide (NHPI)-mediated electrocatalytic oxidation using phenylacetate derivatives as template substrates were first reported for benzylic C[sbnd]H oxidation to oxygenated and non-oxygenated products. DFT calculation indicates that the hydrogen-atom transfer (HAT) process between phthalimido-N-oxyl (PINO) and substrate is a rate-determined step. Aromatic α-keto esters and 2-((1,3-dioxoisoindolin-2-yl)oxy)-2-aryl acetate obtained by cross-coupling between benzylic radical and PINO can be selectively synthesized through controlling the concentration of PINO radical. This method provides a deep understanding for selective weak C[sbnd]H oxidation using NHPI as redox mediator.
- Xu, Leitao,Yi, Yangjie,Hu, Sideng,Ye, Jiao,Hu, Aixi
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- Stereoselective Synthesis of Dihydrocoumarins via [1,2]-Phospha-Brook Rearrangement in Three-Component Coupling Reaction of α-Ketoesters, o-Quinone Methides, and Dialkyl Phosphites
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A highly regio- and diastereoselective approach for the synthesis of phosphate substituted dihydrocoumarins via Br?nsted base catalyzed [1,2]-phospha-Brook rearrangement is reported. The two-step, one-pot Michael addition of α-phosphonyloxy enolates proceeds by coupling of dialkyl phosphite and α-ketoesters to o-quinone methides, followed by an intramolecular cyclization, providing 3,4-dihydrocoumarin frameworks.
- Kaur, Ravneet,Singh, Dipak,Singh, Ravi P.
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p. 15702 - 15711
(2021/11/01)
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- Copper on charcoal: Cu0nanoparticle catalysed aerobic oxidation of α-diazo esters
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By using a charcoal supported nano Cu0catalyst (Cu/C), a highly efficient oxidation of α-diazo esters to α-ketoesters with molecular oxygen as the sole oxidant has been developed. In the presence of the Cu/C catalyst, 2-aryl-α-diazo esters with both electron-donating and electron-withdrawing groups can be oxidized to the corresponding α-ketoesters efficiently. Furthermore, this Cu/C catalyst can catalyse the reaction of aryl α-diazo ester with water to form aryl ketoester, 2-aryl-2-hydroxyl acetate ester and 2-aryl acetate ester. In this case, water is split by α-diazo ester, and the diazo group is displaced by the oxygen or hydrogen atom in water. Mechanistic investigation showed that the reaction of α-diazo ester with oxygen proceeds through a radical pathway. In the presence of 2,2,6,6-tetramethyl piperidine nitrogen oxide, the reaction of α-diazo ester with oxygen is dramatically inhibited. Furthermore, the reaction of α-diazo ester with water is investigated by an isotopic tracer method, and GCMS detection showed that a disproportionation reaction occurred between α-diazo ester and water.
- Chu, Changhu,Dong, Wenwen,Lin, Jia,Teng, Jiangge,Wang, Zhiwei,Zhao, Rong
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p. 6120 - 6126
(2021/07/21)
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- Chemo- And diastereoselective synthesis of pyrrolidines from aroylformates and δ-tosylamino enones via P(NMe2)3-mediated reductive amination/base-catalyzed michael addition cascade
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A novel P(NMe2)3-mediated tandem (1 + 4) annulation between aroylformates and δ-tosylamino enones has been developed that affords a facile synthesis of functionalized pyrrolidines in moderate to excellent yields with exclusive chemoselectivity and high diastereoselectivity. Mechanistic investigation reveals that the reaction proceeds through an unprecedented P(NMe2)3-mediated reductive amination/base-catalyzed Michael addition cascade. The reaction herein also represents the first study of the reactivity patterns of the Kukhtin-Ramirez adducts toward ambiphilic nucleophile-electrophiles.
- Liu, Rongfang,Liu, Jialin,Cao, Jilei,Li, Ruifeng,Zhou, Rong,Qiao, Yan,Gao, Wen-Chao
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supporting information
p. 6922 - 6926
(2020/09/15)
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- Copper(I)-catalyzed aerobic oxidation of α-diazoesters
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A practical Cu-catalyzed oxidation of α-diazoesters to α-ketoesters using molecular oxygen as an oxidant has been developed. Both electron-poor and electron-rich aryl α-diazoesters are suitable substrates and provide the α-ketoesters in good yields. In this oxidative system, α-diazo-β-ketoesters are also compatible as substrates but unexpectedly furnish α-ketoesters via C-C bond cleavage, rather than the vicinal tricarbonyl products.
- Xu, Changming,Bai, Lei,Wang, Yongchang
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p. 12579 - 12584
(2020/11/09)
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- EP300/CREBBP INHIBITOR
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The present invention provides a compound having excellent histone acetyltransferase inhibitory activity against EP300 and/or CREBBP, or a pharmacologically acceptable salt thereof. The compound is represented by the following formula (1) or a pharmacologically acceptable salt thereof: wherein ring Q1, ring Q2, R1, R2, R3 and R4 respectively have the same meanings as defined in the specification.
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Paragraph 0363; 0364
(2020/05/30)
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- Scope and limitations of reductive amination catalyzed by half-sandwich iridium complexes under mild reaction conditions
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The conversion of aldehydes and ketones to 1° amines could be promoted by half-sandwich iridium complexes using ammonium formate as both the nitrogen and hydride source. To optimize this method for green chemical synthesis, we tested various carbonyl substrates in common polar solvents at physiological temperature (37 °C) and ambient pressure. We found that in methanol, excellent selectivity for the amine over alcohol/amide products could be achieved for a broad assortment of carbonyl-containing compounds. In aqueous media, selective reduction of carbonyls to 1° amines was achieved in the absence of acids. Unfortunately, at Ir catalyst concentrations of 1 mM in water, reductive amination efficiency dropped significantly, which suggest that this catalytic methodology might be not suitable for aqueous applications where very low catalyst concentration is required (e.g., inside living cells).
- Nguyen, Dat P.,Sladek, Rudolph N.,Do, Loi H.
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supporting information
(2020/07/15)
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- Ambient and aerobic carbon-carbon bond cleavage toward α-ketoester synthesis by transition-metal-free photocatalysis
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The α-oxoesterification of the CC double bond in readily available enaminones enabling efficient synthesis of α-ketoesters is developed. The reactions showing general tolerance to the reactions of primary and secondary alcohols proceed well under air via Rose Bengal (RB)-based photocatalysis. Particularly, this mild synthetic method has been discovered to tolerate various polyhydroxylated substrates such as phenolic alcohol, diols and triols with an excellent selectivity of mono-oxoesterification. What is more noteworthy is that α-ketoester functionalized 16-dehydropregnenolone acetate resulting from the elaboration on a natural product has been obtained practically.
- Yu, Qing,Zhang, Yating,Wan, Jie-Ping
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supporting information
p. 3436 - 3441
(2019/06/24)
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- Magnesium Aldimines Prepared by Addition of Organomagnesium Halides to 2,4,6-Trichlorophenyl Isocyanide: Synthesis of 1,2-Dicarbonyl Derivatives
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The selective addition of organomagnesium reagents to 2,4,6-trichlorophenyl isocyanide leading to magnesiated aldimines is reported. These aldimines react with Weinreb amides, ketones, or carbonates to provide the corresponding carbonyl derivatives after acidic cleavage. This allows for an efficient synthesis of 1,2-dicarbonyl compounds and α-hydroxy ketones.
- Schw?rzer, Kuno,Bellan, Andreas,Z?schg, Maximilian,Karaghiosoff, Konstantin,Knochel, Paul
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supporting information
p. 9415 - 9418
(2019/05/10)
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- Exploiting Cofactor Versatility to Convert a FAD-Dependent Baeyer–Villiger Monooxygenase into a Ketoreductase
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Cyclohexanone monooxygenases (CHMOs) show very high catalytic specificity for natural Baeyer–Villiger (BV) reactions and promiscuous reduction reactions have not been reported to date. Wild-type CHMO from Acinetobacter sp. NCIMB 9871 was found to possess an innate, promiscuous ability to reduce an aromatic α-keto ester, but with poor yield and stereoselectivity. Structure-guided, site-directed mutagenesis drastically improved the catalytic carbonyl-reduction activity (yield up to 99 %) and stereoselectivity (ee up to 99 %), thereby converting this CHMO into a ketoreductase, which can reduce a range of differently substituted aromatic α-keto esters. The improved, promiscuous reduction activity of the mutant enzyme in comparison to the wild-type enzyme results from a decrease in the distance between the carbonyl moiety of the substrate and the hydrogen atom on N5 of the reduced flavin adenine dinucleotide (FAD) cofactor, as confirmed using docking and molecular dynamics simulations.
- Xu, Jian,Peng, Yongzhen,Wang, Zhiguo,Hu, Yujing,Fan, Jiajie,Zheng, He,Lin, Xianfu,Wu, Qi
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supporting information
p. 14499 - 14503
(2019/09/17)
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- Combined Photoredox/Enzymatic C?H Benzylic Hydroxylations
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Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value-added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single-flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.
- Betori, Rick C.,May, Catherine M.,Scheidt, Karl A.
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supporting information
p. 16490 - 16494
(2019/11/03)
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- Visible Light Promotes Decyanation Esterification Reaction of β - Ketonitriles with Dioxygen and Alcohols to α-Ketoesters
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A green and mild method has been developed for the conversion of β-ketonitriles into α-ketoesters under catalyst-free conditions. A plausible mechanism is that visible light promotes singlet oxygen generation to form the products through oxidative C-H bond functionalization and C-C σ -bond cleavage.
- Xu, Chen,Zhang, Nan-Nan,Li, Xiao-Ji,Ge, Yan-Qin,Diao, Pin-Hui,Guo, Cheng
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supporting information
p. 1065 - 1070
(2018/05/01)
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- Diastereo- and Enantioselective Synthesis of Fluorine Motifs with Two Contiguous Stereogenic Centers
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The synthesis of chiral fluorine containing motifs, in particular, chiral fluorine molecules with two contiguous stereogenic centers, has attracted much interest in research due to the limited number of methods available for their preparation. Herein, we report an atom-economical and highly stereoselective synthesis of chiral fluorine molecules with two contiguous stereogenic centers via azabicyclo iridium-oxazoline-phosphine-catalyzed hydrogenation of readily available vinyl fluorides. Various aromatic, aliphatic, and heterocyclic systems with a variety of functional groups were found to be compatible with the reaction and provide the highly desirable product as single diastereomers with excellent enantioselectivities.
- Ponra, Sudipta,Rabten, Wangchuk,Yang, Jianping,Wu, Haibo,Kerdphon, Sutthichat,Andersson, Pher G.
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supporting information
p. 13878 - 13883
(2018/10/24)
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- CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.
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Paragraph 00234; 00576; 00577
(2018/07/29)
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- Three-Component Activation/Alkynylation/Cyclocondensation (AACC) Synthesis of Enhanced Emission Solvatochromic 3-Ethynylquinoxalines
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2-Substituted 3-ethynylquinoxaline chromophores can be readily synthesized by a consecutive activation–alkynylation–cyclocondensation (AACC) one-pot sequence in a three-component manner. In comparison with the previously published four-component glyoxylation starting from electron-rich π-nucleophiles, the direct activation of (hetero)aryl glyoxylic acids allows the introduction of substituents that cannot be directly accessed by glyoxylation. By introducing N,N-dimethylaniline as a strong donor in the 2-position, the emission solvatochromicity of 3-ethynylquinoxalines can be considerably enhanced to cover the spectral range from blue–green to deep red–orange with a single chromophore in a relatively narrow polarity window. The diversity-oriented nature of the synthetic multicomponent reaction concept enables comprehensive investigations of structure–property relationships by Hammett correlations and Lippert–Mataga analysis, as well as the elucidation of the electronic structure of the emission solvatochromic π-conjugated donor–acceptor systems by DFT and time-dependent DFT calculations with the PBEh1PBE functional for a better reproduction of the dominant charge-transfer character of the longest wavelength absorption band.
- Merkt, Franziska K.,H?wedes, Simon P.,Gers-Panther, Charlotte F.,Gruber, Irina,Janiak, Christoph,Müller, Thomas J. J.
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p. 8114 - 8125
(2018/04/02)
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- Discovery of novel 2-(3-phenylpiperazin-1-yl)-pyrimidin-4-ones as glycogen synthase kinase-3β inhibitors
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We herein describe the results of further evolution of glycogen synthase kinase (GSK)-3β inhibitors from our promising compounds containing a 2-phenylmorpholine moiety. Transformation of the morpholine moiety into a piperazine moiety resulted in potent GSK-3β inhibitors. SAR studies focused on the phenyl moiety revealed that a 4-fluoro-2-methoxy group afforded potent inhibitory activity toward GSK-3β. Based on docking studies, new hydrogen bonding between the nitrogen atom of the piperazine moiety and the oxygen atom of the main chain of Gln185 has been indicated, which may contribute to increased activity compared with that of the corresponding phenylmorpholine analogues. Effect of the stereochemistry of the phenylpiperazine moiety is also discussed.
- Usui, Yoshihiro,Uehara, Fumiaki,Hiki, Shinsuke,Watanabe, Kazutoshi,Tanaka, Hiroshi,Shouda, Aya,Yokoshima, Satoshi,Aritomo, Keiichi,Adachi, Takashi,Fukunaga, Kenji,Sunada, Shinji,Nabeno, Mika,Saito, Ken-Ichi,Eguchi, Jun-ichi,Yamagami, Keiji,Asano, Shouichi,Tanaka, Shinji,Yuki, Satoshi,Yoshii, Narihiko,Fujimura, Masatake,Horikawa, Takashi
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p. 3726 - 3732
(2017/07/27)
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- Copper-catalyzed TEMPO oxidative cleavage of 1,3-diketones and β-keto esters for the synthesis of 1,2-diketones and α-keto esters
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A copper-catalyzed efficient and practical method has been developed for the synthesis of 1,2-diketones and α-keto esters. TEMPO was used as a radical initiator and scavenger, oxidizing the cleavage of α-methylene of 1,3-diketones and β-keto esters to form 1,2-diketones and α-keto esters. This method provided a general way for the formation of 1,2-dicarbonyl compounds.
- Zhou, Peng-Jun,Li, Cheng-Kun,Zhou, Shao-Fang,Shoberu, Adedamola,Zou, Jian-Ping
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p. 2629 - 2637
(2017/04/03)
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- Switchable C-H Functionalization of N-Tosyl Acrylamides with Acryloylsilanes
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A controllable Rh-catalyzed protocol to access alkylation and alkenylation-annulation of N-tosyl acrylamide with acryloyl silane is reported. In contrast to the directing group or catalyst-dependent divergent sp2 C-H alkylation/alkenylation, the intrinsic property of acryloylsilane allows the switchable reaction manifold, thereby affording either alkylation or annulation products with slight modification of the reaction conditions.
- Song, Shengjin,Lu, Ping,Liu, Huan,Cai, Sai-Hu,Feng, Chao,Loh, Teck-Peng
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supporting information
p. 2869 - 2872
(2017/06/13)
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- α-Alkoxycarbonyl-α-hydroxy secondary amides from a carbamoylsilane and α-ketoesters
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The addition of N-methoxymethyl-N-organylcarbamoyl(trimethyl)silane to α-ketoesters in anhydrous toluene at 60 °C afforded α-alkoxycarbonyl-α-siloxy amides in high yields (75–96%). The methoxymethyl was used as an amino protecting group and could be easily converted into hydrogen atom by simple acid hydrolysis leading to α-alkoxycarbonyl-α- hydroxy secondary amides.
- Li, Weidong,Han, Yuling,Chen, Jianxin
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p. 5813 - 5819
(2017/09/05)
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- Catalytic formal cycloadditions between anhydrides and ketones: Excellent enantio and diastereocontrol, controllable decarboxylation and the formation of adjacent quaternary stereocentres
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It has been shown for the first time that enolisable anhydrides can participate in highly efficient and diastereo/enantioselective additions to activated ketones. In these reactions the anhydride component formally acts (initially) as the nucleophilic component. These processes are promoted by novel, readily prepared urea-substituted cinchona alkaloid-derived catalysts at low loadings under mild conditions. Three classes of enolisable anhydride and three different types of activated ketone were shown to be compatible with the process-generating a diverse range of structurally distinct and densely functionalised lactone products with the formation of two new stereocentres, one of which is quaternary. In one example, a product incorporating two contiguous quaternary stereocentres (one all carbon) was formed with outstanding enantiocontrol. It has been shown in the case of glutaconic anhydride derivatives that the cycloaddtion process is reversible, and can be accompanied by decarboxylation and olefin isomerisation. Reaction conditions can be modified to give access to three types of product with good-excellent ee.
- Cornaggia, Claudio,Gundala, Sivaji,Manoni, Francesco,Gopalasetty, Nagaraju,Connon, Stephen J.
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supporting information
p. 3040 - 3046
(2016/03/19)
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- Rhodium-Catalyzed Hydrocarboxylation of Olefins with Carbon Dioxide
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The catalytic hydrocarboxylation of styrenes derivatives and α,β-unsaturated carbonyl compounds with CO2(101.3 kPa) in the presence of an air-stable rhodium catalyst was explored. The combination of [RhCl(cod)]2(cod = cyclooctadiene) as a catalyst and diethylzinc as a hydride source allowed for effective hydrocarboxylation and provided the corresponding α-aryl carboxylic acids in moderate to excellent yields. In this catalytic process with carbon dioxide, intervention of the RhI–H species, which could be generated from the RhIcatalyst and diethylzinc, was clarified. Significantly, the catalytic asymmetric hydrocarboxylation of α,β-unsaturated esters with carbon dioxide was also performed by employing a cationic rhodium complex possessing (S)-(–)-4,4′-bi-1,3-benzodioxole-5,5′-diylbis(diphenylphosphine) [(S)-SEGPHOS] as a chiral diphosphine ligand. A plausible model for asymmetric induction was proposed by determination of the absolute configuration of the product.
- Kawashima, Shingo,Aikawa, Kohsuke,Mikami, Koichi
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supporting information
p. 3166 - 3170
(2016/07/19)
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- Copper(II)-Catalyzed Benzylic C(sp3)-H Aerobic Oxidation of (Hetero)Aryl Acetimidates: Synthesis of Aryl-α-ketoesters
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A straightforward method is developed in this paper for the synthesis of α-ketoesters through copper-catalyzed aerobic oxidation of (hetero)aryl acetimidates using molecular oxygen as a sustainable oxidant. The reaction represents the first example of the direct synthesis of aryl-α-ketoesters from arylacetimidates through the aerobic oxidation of a benzylic C(sp3)-H (CO) bond in moderate to good yield. This transformation occurs under mild reaction conditions with a wide range of substrates and utilizes a readily available oxidant and catalyst. The synthetic utility of this transformation is demonstrated through scaled-up synthesis. A plausible reaction mechanism is also proposed.
- Kumar, Yogesh,Jaiswal, Yogesh,Kumar, Amit
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p. 12247 - 12257
(2016/12/23)
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- Novel Synthesis of α-Keto Esters and Amides by an sp3 C-H Oxidation of Nitromethyl Aryl Ketones Promoted by Ion-Supported (Diacetoxyiodo)benzene
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A simple and efficient method is described for the preparation of α-keto esters or amides from nitromethyl aryl ketones. In the presence of nucleophiles (alcohols or amines), the ion-supported (di-acetoxyiodo)benzene-promoted sp3 C-H oxidation of nitromethyl aryl ketones proceeded efficiently under mild conditions to give the corresponding α-keto esters and amides in moderate to good yields. This is the first reported use of (diacetoxyiodo)benzene in the synthesis of α-keto esters and amides. The reaction is ecofriendly and has the -advantages of mild conditions, short reaction times, and a recyclable reagent.
- Jiang, Xiaoying,Gan, Bing,Liu, Jiwei,Xie, Yuanyuan
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supporting information
p. 2737 - 2741
(2016/11/25)
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- 2-Oxo promoted hydrophosphonylation & aerobic intramolecular nucleophilic displacement reaction
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Highly efficient catalyst free methods for the synthesis of α-hydroxy-β-oxophosphonates and α-oxoesters have been described. The existence of a 2-oxo group in α-oxoaldehydes is a key factor in promoting the reaction of the tervalent phosphite form towards 2-oxoaldehydes in the synthesis of α-hydroxy-β-oxophosphonates. The in situ activated α-C-H atom of α-hydroxy-β-oxophosphonates sustains aerobic intramolecular nucleophilic displacement in a curious way to produce α-oxoester.
- Battula, Satyanarayana,Battini, Narsaiah,Singh, Deepika,Ahmed, Qazi Naveed
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supporting information
p. 8637 - 8641
(2015/08/24)
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- A novel method for synthesis of α-keto esters with phenyliodine(III) diacetate
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A rapid and efficient synthesis of α-keto esters from β-ketonitriles using phenyliodine(III) diacetate is reported. This protocol gave α-keto esters in good yields. This is the first time to report the application of hypervalent iodine(III) reagents in the synthesis of α-keto esters. A plausible reaction mechanism is proposed.
- Xie, Yuanyuan,Liu, Jiwei,Huang, Yingyi,Yao, Lixia
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supporting information
p. 3793 - 3795
(2015/06/08)
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- Alkyl halide-free heteroatom alkylation and epoxidation facilitated by a recyclable polymer-supported oxidant for the in-flow preparation of diazo compounds
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Highly reactive metal carbenes, generated from simple ketones via diazo compounds, including diazoamides and -phosphonates, using a recyclable reagent inflow, are transient but versatile electrophiles for heteroatom alkylation reactions and for epoxide formation. The method produces no organic waste, with the only byproducts being water, KI and nitrogen, without the attendant hazards of isolation of intermediate diazo compounds.
- Nicolle, Simon M.,Hayes, Christopher J.,Moody, Christopher J.
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supporting information
p. 4576 - 4579
(2015/03/18)
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- Rhodium(iii)-catalyzed C-H allylation of electron-deficient alkenes with allyl acetates
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Rhodium-catalyzed C-H allylation of acrylamides with allyl acetates is reported. The use of weakly coordinating directing group resulted in high reaction efficiency, broad functionality tolerance and excellent γ-selectivity, which opens a new synthetic pathway for the access of 1,4-diene skeletons.
- Feng, Chao,Feng, Daming,Loh, Teck-Peng
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supporting information
p. 342 - 345
(2015/01/09)
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- Rhodium(III)-catalyzed olefinic C-H alkynylation of acrylamides using tosyl-imide as directing group
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The Rh(III)-catalyzed C-H alkynylation of acrylamide derivative is realized using a hypervalent alkynyl iodine reagent. The use of a weakly coordinating directing group proved to be of critical importance. This reaction displays broad functional group tolerance and high efficiency, which opens a new synthetic pathway to access functionalized 1,3-enyne skeletons.
- Feng, Chao,Feng, Daming,Luo, Yang,Loh, Teck-Peng
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supporting information
p. 5956 - 5959
(2015/01/08)
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- Synthesis, biological evaluation, and docking analysis of a novel family of 1-methyl-1H-pyrrole-2,5-diones as highly potent and selective cyclooxygenase-2 (COX-2) inhibitors
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As a continuous research for discovery of new COX-2 inhibitors, we present the simple chemical synthesis, in vitro biological screening, and molecular docking study of 1H-pyrrole-2,5-dione derivatives. New synthetic compounds were evaluated for the inhibitory activities on LPS-induced PGE2 production in RAW 264.7 macrophage cells as well as the COX-1 and COX-2 inhibitory potency. Among them, compound 9d (MPO-0029) was identified as more potent and selective COX-2 inhibitor [PGE2 IC50 = 8.7 nM, COX-2 IC50 = 6.0 nM; COX-2 selectivity index (SI) = >168] than celecoxib. Molecular docking experiments were further performed against COX-2 and COX-1 isozymes to determine their probable binding models. Results of molecular docking studies revealed that compound 9d (MPO-0029) has stronger binding interaction with COX-2 than with COX-1 isozyme, and provided successfully complementary theoretical support for the obtained experimental biological data.
- Kim, Kyung Ju,Choi, Min Ji,Shin, Ji-Sun,Kim, Minju,Choi, Hye-Eun,Kang, Seoung Mook,Jin, Jae Ho,Lee, Kyung-Tae,Lee, Jae Yeol
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p. 1958 - 1962
(2014/04/17)
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- Rhodium-catalyzed intermolecular reaction of alkyl azides with diazo(aryl)acetates
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An efficient intermolecular interception of alkyl azides by diazo(aryl)acetates was achieved in the presence of dirhodium tetraoctanoate. The initial products were unstable α-imino esters, and overaddition of carbenoids to the C-N double bonds was avoided. After acidic workup, the corresponding α-keto esters were obtained in good to excellent yields. Georg Thieme Verlag Stuttgart New York.
- Gu, Peiming,Wu, Xiu-Ping,Su, Yan,Li, Xue-Qiang,Xue, Ping,Li, Rui
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supporting information
p. 535 - 538
(2014/03/21)
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- Reactions of organolithiums with dialkyl oxalates. A flow microreactor approach to synthesis of functionalized α-keto esters
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Reactions of functionalized aryllithiums with dialkyl oxalates were achieved using a flow microreactor to obtain α-keto esters with high selectivity by virtue of fast 1:1 micromixing.
- Nagaki, Aiichiro,Ichinari, Daisuke,Yoshida, Jun-Ichi
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supporting information
p. 3242 - 3244
(2013/05/08)
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- Direct asymmetric aldol addition-isomerization of α,β- unsaturated γ-butyrolactam with aryl α-ketoesters: Synthesis of MBH-type products
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A highly efficient direct asymmetric aldol addition-isomerization reaction at the α-position of α,β-unsaturated γ-butyrolactam and aryl α-ketoesters by using a bifunctional thiourea catalyst was achieved. Morita-Baylis-Hillman type adducts containing a quaternary stereocenter can be obtained in high yields and with excellent enantioselectivities (up to 99% ee). The Royal Society of Chemistry 2013.
- Zhang, Jinlong,Liu, Xihong,Ma, Xiaojuan,Wang, Rui
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supporting information
p. 3300 - 3302
(2013/06/04)
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- 2-Aryl-2-nitroacetates as central precursors to aryl nitromethanes, α-ketoesters, and α-amino acids
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Nitroarylacetates are useful small molecular building blocks that act as precursors to α-ketoesters and aryl nitromethanes as well as α-amino acids. Methods were developed that produce each of these compound types in good yields. Two different conditions
- Metz, Alison E.,Kozlowski, Marisa C.
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p. 717 - 722
(2013/02/25)
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- Directing-group-assisted copper-catalyzed olefinic trifluoromethylation of electron-deficient alkenes
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Assistance provided: The directing group in the title reaction not only activates the substrates but also allows the stereospecific formation of cis-trifluoromethylated products. The reaction is operationally simple and tolerates a wide variety of functional groups, thus providing an efficient method for the stereoselective synthesis of β-CF3-functionalized acrylamide derivatives. Copyright
- Feng, Chao,Loh, Teck-Peng
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supporting information
p. 122414 - 122417
(2013/12/04)
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- Simplified procedure for TEMPO-catalyzed oxidation: Selective oxidation of alcohols, α-hydroxy esters, and amides using TEMPO and calcium hypochlorite
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A wide range of primary and secondary multifunctional alcohols, α-hydroxyamides, and α-hydroxyesters were oxidized to their corresponding aldehydes, ketones, α-ketoamides, and α-ketoesters under mild reaction conditions using 2,2,6,6-tetramethylpiperidine-1-oxyl as a catalyst with calcium hypochlorite as an oxidant [TEMPO-Ca(OCl)2]. This simplified method does not require any transition metals, acids, or bases and demonstrates controlled and selective oxidation of structurally diverse alcohols, affording moderate to excellent yields at room temperature.
- Reddy, Sabbasani Rajasekhara,Stella, Selvaraj,Chadha, Anju
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experimental part
p. 3493 - 3503
(2012/09/22)
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- Highly homogeneous stereocontrolled construction of quaternary hydroxyesters by addition of dimethylzinc to α-ketoesters promoted by chiral perhydrobenzoxazines and B(OEt)3
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A highly efficient enantioselective addition of Me2Zn to α-ketoesters, assisted by a chiral perhydro-1,3-benzoxazine ligand, is described. This novel catalytic system offers homogeneous elevated enantioselectivities in the preparation of α-hydroxyesters that bear a quaternary stereocenter, with a minor dependence on electronic and steric effects when aromatic, heteroaromatic, or aliphatic α-ketoesters are employed. The catalyst can be recovered and reused without loss of activity.
- Infante, Rebeca,Nieto, Javier,Andres, Celia
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supporting information; experimental part
p. 4375 - 4379
(2012/05/20)
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- Catalytic enantioselective protonation of α-oxygenated ester enolates prepared through phospha-brook rearrangement
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(Chemical Equation Presented) Phosphonates go chiral: The organocatalytic enantioselective reaction of α-ketoesters with phosphites using cinchona alkaloids and Na2CO3 has afforded α-phosphonyloxy esters with high enantioselectivities (see scheme). This process allows the formation of both enantiomers of the product. A catalyst loading of as low as 2 mol% does not result in a significant decrease of the enantioselectivity.
- Hayashi, Masashi,Nakamura, Shuichi
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supporting information; experimental part
p. 2249 - 2252
(2011/04/16)
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- Enantioselective enolate protonation in sulfamichael addition to r-substituted n-acryloyloxazolidin-2-ones with bifunctional organocatalyst
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Organocatalytic conjugate addition of thiols to R-substituted N-acryloyloxazolidin-2-ones followed by asymmetric protonation has been studied in the presence of cinchona alkaloid derived thioureas. Both of the enantiomers are accessible with the same level of enantioselectivity using pseudoenantiomeric quinine/quinidine derived catalysts. The addition/protonation products have been converted to useful biologically active molecules. 2011 American Chemical Society.
- Rana, Nirmal K.,Singh, Vinod K.
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supporting information; experimental part
p. 6520 - 6523
(2012/02/01)
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- Development of decarboxylative coupling processes for the synthesis of azomethines and ketones
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A bimetallic catalyst system has been developed that allows the synthesis of azomethines by a one-pot three-component decarboxylative coupling, starting from simple, nontoxic precursors, i.e. potassium α-oxo carboxylates, aryl halides and primary amines. In the presence of 15 mol-% copper/phenanthroline and 1 mol-% Pd/dppf, a wide range of valuable imines is conveniently accessible in high yields at 100 °C, an unprecedentedly low temperature for redox-neutral decarboxylative cross-coupling reactions. Hydrogenation of the azomethine products leads to secondary amines. Alternatively, they can be hydrolyzed in situ to aryl ketones. The resulting ketone synthesis via azomethine intermediates is also of interest as it gives higher yields at much lower temperatures than the direct decarboxylative coupling of α-oxo carboxylates with aryl halides. A convenient synthesis of azomethines by a one-pot three-component decarboxylative coupling, starting from potassium α-oxo carboxylates, aryl halides and primary amines is described. Combined with in situ hydrolysis, ketones are obtained. Thisamine-mediated ketone synthesis gives higher yields at lower temperatures than the direct coupling of α-oxo carboxylates. Copyright
- Collet, Florence,Song, Bingrui,Rudolphi, Felix,Goossen, Lukas J.
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experimental part
p. 6486 - 6501
(2011/12/05)
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- BF3 · Et2O-induced decomposition of ethyl 2-diazo-3-hydroxy-3,3-diarylpropanoates in acetonitrile: A novel approach to 2,3-diaryl β-enamino ester derivatives
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The BF3·Et2O-induced decomposition of ethyl 2-diazo-3-hydroxy-3,3-diarylpropanoates, prepared by the addition of a series of benzophenones to ethyl diazo(lithio)acetate, is reported and studied. By using acetonitrile as a solvent, the corresponding N-acyl β-enamino ester derivatives are obtained in good yields and with a diverse regioselectivity as the result of 1,2-aryl migration in the vinyl cation intermediates. The factors that govern the migratory aptitude as well as the mechanistic aspects of the reaction are discussed.
- Gioiello, Antimo,Venturoni, Francesco,Natalini, Benedetto,Pellicciari, Roberto
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supporting information; experimental part
p. 3520 - 3523
(2009/09/30)
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- NON-STEROIDAL PROGESTERONE RECEPTOR MODULATORS
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The present invention relates to non-steroidal progesterone receptor modulators of the general formula 1, the use of the progesterone receptor modulators for the manufacture of medicaments, and pharmaceutical compositions which comprise these compounds. The compounds according to the invention are suitable for the therapy and prophylaxis of gynaecological disorders such as endometriosis, leiomyomas of the uterus, dysfunctional bleeding and dysmenorrhoea, and for the therapy and prophylaxis of hormone-dependent tumours and for use for female fertility control and for hormone replacement therapy.
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Page/Page column 63-64
(2009/04/24)
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- N-SUBSTITUTED GLYCINE DERIVATIVES: HYDROXYLASE INHIBITORS
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The invention described herein relates to certain pyridazinedione N-substituted glycine derivatives of formula (I) which are antagonists of HIF prolyl hydroxylases and are useful for treating diseases benefiting from the inhibition of this enzyme, anemia being one example
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Page/Page column 48-49
(2008/12/07)
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- CeCl3·7H2O: An effective additive in ru-catalyzed enantioselective hydrogenation of aromatic α-ketoesters
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(Chemical Equation Presented) In the presence of catalytic amounts of CeCl3·7H2O, [RuCl(benzene)(S)-SunPhos]Cl is a highly effective catalyst for the asymmetric hydrogenation of aromatic α-ketoesters. A variety of ethyl α-hydroxy-α-arylacetates have been prepared in up to 98.3% ee with a TON up to 10 000. Challenging aromatic α-ketoesters with ortho substituents are also hydrogenated with high enantioselectivities. The addition of CeCl3·7H2O not only improves the enantioselectivity but also enhances the stability of the catalyst. The ratio of CeCl3·7H2O to [RuCl(benzene)(S)-SunPhos]Cl plays an important role in the hydrogenation reaction with a large substrate/catalyst ratio.
- Meng, Qinghua,Sun, Yanhui,Ratovelomanana-Vidal, Virginie,Genet, Jean Pierre,Zhang, Zhaoguo
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p. 3842 - 3847
(2008/09/21)
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- Synthesis of α-keto esters by the rhodium-catalysed reaction of cyanoformate with arylboronic acids
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An arylrhodium(i) species selectively reacts with the cyano group of ethyl cyanoformate to afford the corresponding α-keto ester in good yield. The Royal Society of Chemistry.
- Shimizu, Hiroshi,Murakami, Masahiro
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p. 2855 - 2857
(2008/02/08)
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- Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors
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The new analogue 2 of combretastatin A-4 was discovered to be an inhibitor of tubulin polymerization with an IC50 of 7.6 μM and reduced angiogenesis in the in vivo chick embryo model. Interestingly, in a series of 2,3-diarylmaleimides closely r
- Peifer, Christian,Stoiber, Thomas,Unger, Eberhard,Totzke, Frank,Sch?chtele, Christoph,Marmé, Dieter,Brenk, Ruth,Klebe, Gerhard,Schollmeyer, Dieter,Dannhardt, Gerd
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p. 1271 - 1281
(2007/10/03)
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- Reliable and versatile synthesis of 2-aryl-substituted cinnamic acid esters
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2-Aryl-substituted phosphono acetates can be readily synthesized by a four-step sequence from the respective arenes. Succeeding Horner-Wadsworth- Emmons olefinations provide stereoselectively the 2-aryl cinnamic acid esters even when sensitive moieties are involved. Georg Thieme Verlag Stuttgart.
- Ianni, Alen,Waldvogel, Siegfried R.
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p. 2103 - 2112
(2008/02/02)
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- Synthesis of aryl α-keto esters via the rearrangement of aryl cyanohydrin carbonate esters
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A facile synthesis of aryl α-keto esters is reported involving the rearrangement of aryl cyanohydrin carbonate esters induced by the α-carbanion to the nitrile group generated by LDA. However, under similar conditions, an o-benzyloxycyanohydrin carbonate ester rearranged via a domino reaction leading to 2-phenylbenzofuran-3-carboxylic acid.
- Thasana, Nopporn,Prachyawarakorn, Vilailak,Tontoolarug, Sopchok,Ruchirawat, Somsak
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p. 1019 - 1021
(2007/10/03)
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- N-hydroxyphthalimide/cobalt(II) catalyzed low temperature benzylic oxidation using molecular oxygen
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A variety of (substituted) aryl glyoxylates is formed in good to excellent yield under very mild conditions by direct oxidation of the corresponding arylacetic esters or mandelic acid esters with molecular oxygen and N-hydroxyphthalimide/cobalt(II) acetate as catalyst. Heteroaromatic analogs are more difficult to oxidize with this system. The effect of substitution in the aromatic ring of N-hydroxyphthalimide on the oxidation of ethylbenzene has been studied. Electron withdrawing substituents accelerate the oxidation of ethylbenzene and promote the formation of acetophenone. Electron donating substituents lead to decreased rates of oxidation and enhance the selectivity for 1-phenylethanol. (C) 2000 Elsevier Science Ltd.
- Wentzel, Bastienne B,Donners, Maurice P.J,Alsters, Paul L,Feiters, Martinus C,Nolte, Roeland J.M
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p. 7797 - 7803
(2007/10/03)
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