- Synthesis of 4-cyano pyrroles via mild Knorr reactions with β-ketonitriles
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Mild methods for conducting Knorr chemistry with β-ketonitriles were developed. This enabled the preparation of 4-cyanopenta-substituted pyrroles and gave access to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor potentiators for biol
- Magnus, Nicholas A.,Staszak, Michael A.,Udodong, Uko E.,Wepsiec, James P.
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- Organic photovoltaics of diketopyrrolopyrrole copolymers with unsymmetric and regiorandom configuration of the side units
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Diketopyrrolopyrrole (DPP) is a representative electron acceptor incorporated into narrow-bandgap polymers for organic photovoltaic cells (OPV). Commonly, identical aromatic units are attached to the sides of the DPP unit, forming symmetric DPP polymers. Herein we report the synthesis and characterization of DPP copolymers consisting of unsymmetric configurations of the side aromatics. The unsymmetric DPP copolymer with thienothiophene and benzene side moieties exhibits good solubility owing to the twisted dihedral angle at benzene and regiorandom configuration. A significant shallowing of the highest occupied molecular orbital level is observed in accordance with the electron-donating nature of the side units (benzene, thiophene, and thienothiophene). The overall power conversion efficiencies of the unsymmetric DPPs (2.3-2.4%) are greater than that of the centrosymmetric analogue (0.45%), which is discussed in view of bulk heterojunction morphology, polymer crystallinity, and space-charge-limited current mobilities. This comparative study highlights the effect of unsymmetric design on the molecular stacking and OPV performance of DPP copolymers.
- Aoshima, Kenta,Ide, Marina,Saeki, Akinori
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- Electrochemical Oxidative Cyclization: Synthesis of Polysubstituted Pyrrole from Enamines
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A conceptually novel method for the preparation of pyrrole is described by electrochemical-oxidation-induced intermolecular annulation via enamines. In a simple undivided cell, based on a sodium acetate-facilitated, polysubstituted pyrrole derivations has been facilely synthesized under external oxidant-free condition. This electrosynthetic approach providing an environmentally benign protocol for C?C bond cross-coupling and oxidative annulation, which features unparalleled broad scope of substrates and practicality.
- Chen, Zhiwei,Shi, Guang,Tang, Wei,Sun, Jie,Wang, Wenxing
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supporting information
p. 951 - 955
(2021/02/03)
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- Construction of isoxazolone-fused phenanthridinesviaRh-catalyzed cascade C-H activation/cyclization of 3-arylisoxazolones with cyclic 2-diazo-1,3-diketones
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A Rh(iii)-catalyzed cascade C-H activation/intramolecular cyclization of 3-aryl-5-isoxazolones with cyclic 2-diazo-1,3-diketones was described, leading to the formation of isoxazolo[2,3-f]phenanthridine skeletons. The protocol features the simultaneous one-pot formation of two new C-C/C-N bonds and one heterocycle in moderate-to-good yields with good functional group compatibility. It is amenable to large-scale synthesis and further transformation.
- Hu, Wangcheng,He, Xinwei,Zhou, Tongtong,Zuo, Youpeng,Zhang, Shiwen,Yang, Tingting,Shang, Yongjia
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supporting information
p. 552 - 556
(2021/02/06)
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- Photoinduced Diverse Reactivity of Diazo Compounds with Nitrosoarenes
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A diverse reactivity of diazo compounds with nitrosoarene in an oxygen-transfer process and a formal [2 + 2] cycloaddition is reported. Nitosoarene has been exploited as a mild oxygen source to oxidize an in situ generated carbene intermediate under visible-light irradiation. UV-light-mediated in situ generated ketenes react with nitosoarenes to deliver oxazetidine derivatives. These operationally simple processes exemplify a transition-metal-free and catalyst-free protocol to give structurally diverse α-ketoesters or oxazetidines.
- Roy, Sourav,Kumar, Gourav,Chatterjee, Indranil
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supporting information
p. 6709 - 6713
(2021/09/08)
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- Iridium-Catalyzed Enantioselective and Diastereoselective Hydrogenation of Racemic β’-Keto-β-Amino Esters via Dynamic Kinetic Resolution
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An iridium/f-diaphos catalytic system for the enantioselective hydrogenation of α-substituted β-ketoesters via dynamic kinetic resolution is reported. The desired anti β’-hydroxy-β-amino esters were obtained in moderate to good yields (60–95%) with 72–99% ees and 91:9 to 99:1 drs. This protocol tolerates various functional groups and could be easily conducted on gram scale with lower catalyst loading (TON up to 9100). (Figure presented.).
- He, Jiayin,Huang, An,Ling, Fei,Wang, Shiliang,Wang, Yifan,Wang, Ze,Zhao, Xianghua,Zhong, Weihui
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supporting information
p. 4714 - 4719
(2021/09/02)
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- Promising new inhibitors of tyrosyl-DNA phosphodiesterase I (Tdp 1) combining 4- arylcoumarin and monoterpenoid moieties as components of complex antitumor therapy
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Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme in humans, and a current and promising inhibition target for the development of new chemosensitizing agents due to its ability to remove DNA damage caused by topoisomerase 1 (Top1) poisons such as topotecan and irinotecan. Herein, we report our work on the synthesis and characterization of new Tdp1 inhibitors that combine the arylcoumarin (neoflavonoid) and monoterpenoid moieties. Our results showed that they are potent Tdp1 inhibitors with IC50 values in the submicromolar range. In vivo experiments with mice revealed that compound 3ba (IC50 0.62 μM) induced a significant increase in the antitumor effect of topotecan on the Krebs-2 ascites tumor model. Our results further strengthen the argument that Tdp1 is a druggable target with the potential to be developed into a clinically-potent adjunct therapy in conjunction with Top1 poisons.
- Ayine-tora, Daniel M.,Chand, Raina,Chepanova, Arina A.,Ilina, Ekaterina S.,Kaledin, Vasily I.,Khomenko, Tatyana M.,Korchagina, Dina V.,Lavrik, Olga I.,Leung, Ivanhoe K. H.,Nikolin, Valeriy P.,Patel, Jinal,Popova, Nelly A.,Reynisson, Jóhannes,Salakhutdinov, Nariman F.,Volcho, Konstantin P.,Zakharenko, Alexandra L.,Zakharova, Olga D.
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- Radical Aza-Cyclization of α-Imino-oxy Acids for Synthesis of Alkene-Containing N-Heterocycles via Dual Cobaloxime and Photoredox Catalysis
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Nitrogen-containing heterocycles are prevalent in both naturally and synthetically bioactive molecules. We report herein an unprecedented protocol for radical aza-cyclization of α-imino-oxy acids with pendant alkenes via synergistic photoredox and cobaloxime catalysis. With or without alkenes as the intermolecular cross-coupling partners, the transformation provides a variety of corresponding alkene-containing dihydropyrrole products in satisfactory yields. In the presence of external alkenes, the tandem reaction generates E-selective coupling products with excellent chemo- and stereoselectivity.
- Tu, Jia-Lin,Liu, Jia-Li,Tang, Wan,Su, Ma,Liu, Feng
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supporting information
p. 1222 - 1226
(2020/02/15)
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- An efficient route for the synthesis of N-(1H-benzo[d]imidazol-2-yl)benzamide derivatives promoted by CBr4 in one pot
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A metal-free one-pot method for the synthesis of N-(1H-benzo[d]imidazol-2-yl)benzamide derivatives was proposed mediated by CBr4. The reaction went through ring formation and opening processes with only two protons leaving and the thermodynamically favorable products were selectively formed in moderate to good yields.
- Li, Songhua,Li, Yunyi,Ma, Chen,Xie, Caixia
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- Design, Synthesis, and Biochemical Characterization of Non-Native Antagonists of the Pseudomonas aeruginosa Quorum Sensing Receptor LasR with Nanomolar IC50 Values
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Quorum sensing (QS), a bacterial cell-to-cell communication system mediated by small molecules and peptides, has received significant interest as a potential target to block infection. The common pathogen Pseudomonas aeruginosa uses QS to regulate many of its virulence phenotypes at high cell densities, and the LasR QS receptor plays a critical role in this process. Small molecule tools that inhibit LasR activity would serve to illuminate its role in P. aeruginosa virulence, but we currently lack highly potent and selective LasR antagonists, despite considerable research in this area. V-06-018, an abiotic small molecule discovered in a high-throughput screen, represents one of the most potent known LasR antagonists but has seen little study since its initial report. Herein, we report a systematic study of the structure-activity relationships (SARs) that govern LasR antagonism by V-06-018. We synthesized a focused library of V-06-018 derivatives and evaluated the library for bioactivity using a variety of cell-based LasR reporter systems. The SAR trends revealed by these experiments allowed us to design probes with 10-fold greater potency than that of V-06-018 and 100-fold greater potency than other commonly used N-acyl-l-homoserine lactone (AHL)-based LasR antagonists, along with high selectivities for LasR. Biochemical experiments to probe the mechanism of antagonism by V-06-018 and its analogues support these compounds interacting with the native ligand-binding site in LasR and, at least in part, stabilizing an inactive form of the protein. The compounds described herein are the most potent and efficacious antagonists of LasR known and represent robust probes both for characterizing the mechanisms of LuxR-type QS and for chemical biology research in general in the growing QS field.
- Blackwell, Helen E.,Manson, Daniel E.,Nyffeler, Kayleigh E.,O'Reilly, Matthew C.
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- Compound for treating diabetes and/or related disorders
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The invention discloses a compound for treating diabetes and/or related disorders, specifically a method for preventing, inhibiting and/or reversing amylin amyloid fibril formation, preventing isletsof Langerhans beta-cell death, preventing and/or reversing conversion of soluble human amylin to insoluble human amylin, and preventing and inhibiting and/or reversing cytotoxic amylin fibril formation. The invention also relates to a compound for preparing drugs for preventing and/or treating amylin amyloid-associated diseases.
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Paragraph 0316; 0317; 0318
(2020/05/14)
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- COMPOUNDS FOR TREATING DIABETES AND/OR RELATED CONDITIONS
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Compounds useful for treating or preventing diabetes and related conditions, and for preventing, inhibiting or reversing amylin-amyloid fibril formation, preventing islets of Langerhans (Beta)-cell death, preventing or reversing the transition from soluble human amylin to insoluble human amylin, preventing and inhibiting or reversing cytotoxic amylin fibril formation. The invention relates to compounds of Formula (I) and compounds of Formula (II): (Formulae (I) and (II)).
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Paragraph 00158
(2020/05/21)
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- Double Enzyme-Catalyzed One-Pot Synthesis of Enantiocomplementary Vicinal Fluoro Alcohols
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A double-enzyme-catalyzed strategy for the synthesis of enantiocomplementary vicinal fluoro alcohols through a one-pot, three-step process including lipase-catalyzed hydrolysis, spontaneous decarboxylative fluorination, and subsequent ketoreductase-catalyzed reduction was developed. With this approach, β-ketonic esters were converted to the corresponding vicinal fluoro alcohols with high isolated yields (up to 92percent) and stereoselectivities (up to 99percent). This new cascade process addresses some issues in comparison with traditional methods such as environmentally hazardous reaction conditions and low stereoselectivity outcome.
- Fan, Jiajie,Lin, Xianfu,Peng, Yongzhen,Wang, Anlin,Wu, Qi,Xu, Jian,Xu, Weihua,Yu, Huilei
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supporting information
(2020/07/24)
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- Desymmetrization of meso-dicarbonatecyclohexene with β-Hydrazino carboxylic esters via a Pd-catalyzed allylic substitution cascade
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The desymmetrization of meso-dicarbonatecyclohexene with β-hydrazino carboxylic esters has been achieved via a RuPHOX/Pd-catalyzed allylic substitution cascade for the construction of chiral hexahydrocinnoline derivatives with high performance. Mechanistic studies reveal that the reaction exploits a pathway different from that of our previous work and that the first nitrogen nucleophilic process is the rate-determining step. The protocol could be conducted on a gram scale without any loss of catalytic behavior, and the corresponding chiral hexahydrocinnolines can undergo diverse transformations.
- Xu, Kai,Zheng, Yan,Ye, Yong,Liu, Delong,Zhang, Wanbin
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supporting information
p. 8836 - 8841
(2020/11/30)
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- A Hammett Study of Clostridium acetobutylicum Alcohol Dehydrogenase (CaADH): An Enzyme with Remarkable Substrate Promiscuity and Utility for Organic Synthesis
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Described is a physical organic study of the reduction of three sets of carbonyl compounds by the NADPH-dependent enzyme Clostridium acetobutylicum alcohol dehydrogenase (CaADH). Previous studies in our group have shown this enzyme to display broad substrate promiscuity, yet remarkable stereochemical fidelity, in the reduction of carbonyl compounds, including α-, β- and γ-keto esters (d -stereochemistry), as well as α,α-difluorinated-β-keto phosphonate esters (l -stereochemistry). To better mechanistically characterize this promising dehydrogenase enzyme, we report here the results of a Hammett linear free-energy relationship (LFER) study across three distinct classes of carbonyl substrates; namely aryl aldehydes, aryl β-keto esters and aryl trifluoromethyl ketones. Rates are measured by monitoring the decrease in NADPH fluorescence at 460 nm with time across a range of substrate concentrations for each member of each carbonyl compound class. The resulting v 0 versus [S] data are subjected to least-squares hyperbolic fitting to the Michaelis-Menton equation. Hammett plots of log(V max) versus σ X yield the following Hammett parameters: (i) for p -substituted aldehydes, ρ = 0.99 ± 0.10, ρ = 0.40 ± 0.09; two domains observed, (ii) for p -substituted β-keto esters ρ = 1.02 ± 0.31, and (iii) for p -substituted aryl trifluoromethyl ketones ρ = -0.97 ± 0.12. The positive sign of ρ indicated for the first two compound classes suggests that the hydride transfer from the nicotinamide cofactor is at least partially rate-limiting, whereas the negative sign of ρ for the aryl trifluoromethyl ketone class suggests that dehydration of the ketone hydrate may be rate-limiting for this compound class. Consistent with this notion, examination of the 13 C NMR spectra for the set of p -substituted aryl trifluo romethyl ketones in 2percent aqueous DMSO reveals significant formation of the hydrate (gem -diol) for this compound family, with compounds bearing the more electron-withdrawing groups showing greater degrees of hydration. This work also presents the first examples of the CaADH-mediated reduction of aryl trifluoromethyl ketones, and chiral HPLC analysis indicates that the parent compound α,α,α-trifluoroacetophenone is enzymatically reduced in 99percent ee and 95percent yield, providing the (S)-stereoisomer, suggesting yet another compound class for which this enzyme displays high enantioselectivity.
- Berkowitz, David B.,Kudalkar, Gaurav P.,Lee, Joshua D.,Tiwari, Virendra K.
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supporting information
p. 237 - 247
(2020/02/18)
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- Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes
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Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine-or H2O2-induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.
- Bai, Feifei,Fang, Jianguo,Song, Zi-Long,Zhang, Baoxin
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p. 2214 - 2231
(2020/03/06)
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- Switching of Sulfonylation Selectivity by Nature of Solvent and Temperature: The Reaction of β-Dicarbonyl Compounds with Sodium Sulfinates under the Action of Iron-Based Oxidants
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Selectivity of sulfonylation of β-keto esters with sodium sulfinates under the action of iron(III) salts as oxidants can be regulated by the type of solvent used and the reaction temperature. α-Sulfonyl β-keto esters are obtained when the process is conducted in THF/H2O solution at 40 °C. The change of the solvent to iPrOH/H2O and refluxing of a reaction mixture provides α-sulfonyl esters – the products of successive sulfonylation-deacylation. When β-diketones are applied as starting materials, only α-sulfonyl ketones are formed. The reaction pathway includes sulfonylation of dicabonyl compounds under the action of Fe(III) to form α-sulfonylated dicarbonyl compounds, which are then attacked by a solvent as the nucleophile, resulting in the products of successive sulfonylation-deacylation. Participation of the solvent in the reaction pathway determines the products structure.
- Mulina, Olga M.,Pirgach, Dmitry A.,Nikishin, Gennady I.,Terent'ev, Alexander O.
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supporting information
p. 4179 - 4188
(2019/05/08)
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- Catalytic Mechanism Study on the 1,2- and 1,4-Transfer Hydrogenation of Ketimines and β-Enamino Esters Catalyzed by Axially Chiral Biscarboline-Based Alcohols
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Axial N-O alcohols, which have two large carboline moieties connected to the axis were synthesized and used in catalytic enantioselective 1,2- and 1,4-transfer hydrogenations of total 26 ketimines and β-enamino esters. Excellent levels of enantioselectivity ranging from 91% to 99% were achieved by using catalyst (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide. Interestingly, a mixture of (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide and (aR)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide was also able to provide high enantioselectivities up to 95% that is the same as that using pure (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide. A plausible catalytic mechanism was suggested and total four kinds of transition states (TS) including almost 60 TS structures were investigated using density functional theory (DFT) with different basis sets such as 6-311G(2d,p). The predicted activation energy data are consistent with the experimental results. (Figure presented.).
- Dong, Mengxian,Wang, Jie,Wu, Shijie,Zhao, Yang,Ma, Yangyang,Xing, Yongfei,Cao, Fei,Li, Longfei,Li, Zhenqiu,Zhu, Huajie
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supporting information
p. 4602 - 4610
(2019/08/30)
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- Highly Luminescent Encapsulated Narrow Bandgap Polymers Based on Diketopyrrolopyrrole
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We present the synthesis and characterization of a series of encapsulated diketopyrrolopyrrole red-emitting conjugated polymers. The novel materials display extremely high fluorescence quantum yields in both solution (>70%) and thin film (>20%). Both the absorption and emission spectra show clearer, more defined features compared to their naked counterparts demonstrating the suppression of inter and intramolecular aggregation. We find that the encapsulation results in decreased energetic disorder and a dramatic increase in backbone colinearity as evidenced by scanning tunnelling microscopy. This study paves the way for diketopyrrolopyrrole to be used in emissive solid state applications and demonstrates a novel method to reduce structural disorder in conjugated polymers.
- Leventis, Anastasia,Royakkers, Jeroen,Rapidis, Alexandros G.,Goodeal, Niall,Corpinot, Merina K.,Frost, Jarvist M.,Bu?ar, Dejan-Kre?imir,Blunt, Matthew Oliver,Cacialli, Franco,Bronstein, Hugo
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supporting information
p. 1622 - 1626
(2018/02/17)
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- In situ generation of nitrile oxides from copper carbene and tert -butyl nitrite: Synthesis of fully substituted isoxazoles
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Herein, we present a novel [3 + 2] cycloaddition reaction of β-keto esters with nitrile oxides, which were generated in situ from copper carbene and tert-butyl nitrite. This three-component reaction provides new methodology for the direct synthesis of fully substituted isoxazole derivatives, featuring mild reaction conditions, readily accessible starting materials and simple operation. The experimental studies and DFT calculations suggest that the reaction starts with the generation of the key intermediate nitrile oxides, followed by a [3 + 2] cycloaddition reaction of β-keto esters to give the final isoxazole products.
- Chen, Rongxiang,Ogunlana, Abosede Adejoke,Fang, Shangwen,Long, Wenhao,Sun, Hongmei,Bao, Xiaoguang,Wan, Xiaobing
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supporting information
p. 4683 - 4687
(2018/07/06)
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- Expanding Blaise-Type Reactions towards Indium-Mediated Transformations of α-Bromo-β-keto Esters with Nitriles
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The aim of this work is the identification of mild reaction conditions for the Blaise-type transformation of brominated β-keto esters with nitriles to generate enamino-substituted keto esters. The best results were obtained when a combination of indium metal (0.7 equiv.) with indium trichloride (1.6 equiv.) were applied at 60 °C for 20 to 72 hours, and these conditions could be applied to a broad range of nitriles and a significant number of different β-keto esters. The transformation of aliphatic nitriles proved to be difficult and gave only moderate yields. However, aromatic nitriles gave good yields in many cases. The applicability range of β-keto esters is acceptable while some electron-deficient aryl-substituents on the keto ester were challenging substrates. Nevertheless, we were able to expand the scope of the Blaise-type reaction towards brominated β-keto esters significantly.
- Li, Luomo,Babaoglu, Emre,Harms, Klaus,Hilt, Gerhard
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supporting information
p. 4543 - 4547
(2017/08/30)
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- One-pot multistep mechanochemical synthesis of fluorinated pyrazolones
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Solventless mechanochemical synthesis represents a technique with improved sustainability metrics compared to solvent-based processes. Herein, we describe a methodical process to run one solventless reaction directly into another through multistep mechanochemistry, effectively amplifying the solvent savings. The approach has to consider the solid form of the materials and compatibility of any auxiliary used. This has culminated in the development of a two-step, one-jar protocol for heterocycle formation and subsequent fluorination that has been successfully applied across a range of substrates, resulting in 12 difluorinated pyrazolones in moderate to excellent yields.
- Howard, Joseph L.,Nicholson, William,Sagatov, Yerbol,Browne, Duncan L.
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supporting information
p. 1950 - 1956
(2017/09/27)
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- Bromide-Mediated C-H Bond Functionalization: Intermolecular Annulation of Phenylethanone Derivatives with Alkynes for the Synthesis of 1-Naphthols
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Bromide-mediated intermolecular annulation of phenylethanone derivatives with alkynes has been developed, which allows for the regioselective formation of polysubstituted 1-naphthols. The usage of readily available bromine catalyst, broad substrate scope, and mild conditions make this protocol very practical. Mechanistic investigations reveal that the bromination of phenylethanone derivatives occurs to yield bromo-substituted intermediates, which react in situ with alkynes to furnish the desired 1-naphthols.
- Lu, Tao,Jiang, Ya-Ting,Ma, Feng-Ping,Tang, Zi-Jing,Kuang, Liu,Wang, Yu-Xuan,Wang, Bin
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supporting information
p. 6344 - 6347
(2017/12/08)
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- Reformatsky and Blaise reactions in flow as a tool for drug discovery. One pot diversity oriented synthesis of valuable intermediates and heterocycles
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The application of Reformatsky and Blaise reactions for the preparation of a diverse set of valuable intermediates and heterocycles in a one-pot protocol is described. To achieve this goal, a greener activation protocol for zinc in flow conditions has been developed to introduce this metal efficiently into α-bromoacetates. The organozinc compounds were added to a diverse set of ketones and nitriles to obtain a wide range of functional groups and heterocyclic systems.
- Huck,Berton,De La Hoz,Díaz-Ortiz,Alcázar
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supporting information
p. 1420 - 1424
(2017/05/12)
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- Explicit treatment of active-site waters enhances quantum mechanical/implicit solvent scoring: Inhibition of CDK2 by new pyrazolo[1,5-a]pyrimidines
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We present comprehensive testing of solvent representation in quantum mechanics (QM)-based scoring of protein-ligand affinities. To this aim, we prepared 21 new inhibitors of cyclin-dependent kinase 2 (CDK2) with the pyrazolo[1,5-a]pyrimidine core, whose
- Hylsová, Michaela,Carbain, Benoit,Fanfrlík, Jind?ich,Musilová, Lenka,Haldar, Susanta,K?prülüo?lu, Cemal,Ajani, Haresh,Brahmkshatriya, Pathik S.,Jorda, Radek,Kry?tof, Vladimír,Hobza, Pavel,Echalier, Aude,Paruch, Kamil,Lep?ík, Martin
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p. 1118 - 1128
(2017/01/03)
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- Regioselective Synthesis of Dihydrothiophenes and Thiophenes via the Rhodium-Catalyzed Transannulation of 1,2,3-Thiadiazoles with Alkenes
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A method for the regioselective synthesis of a wide range of dihydrothiophenes was developed from the rhodium-catalyzed transannulation of 1,2,3-thiadiazoles with aliphatic, aromatic, and heteroaromatic alkenes. Tandem rhodium-catalyzed transannulation of 1,2,3-thiadiazoles with alkenes followed by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidation was also demonstrated for the one-pot regioselective synthesis of various thiophenes. Advantages of the present method include a broad substrate scope, wide functional group compatibility, and high regioselectivity.
- Son, Jeong-Yu,Kim, Jonghye,Han, Sang Hoon,Kim, Sung Hong,Lee, Phil Ho
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supporting information
p. 5408 - 5411
(2016/11/06)
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- LIVER X RECEPTOR (LXR) MODULATORS
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Described herein are liver X receptor (LXR) modulators and methods of utilizing LXR modulators in the treatment of dermal diseases, disorders or conditions. Also described herein are pharmaceutical compositions containing such compounds.
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Page/Page column 122
(2015/03/28)
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- QUINOLINES DERIVATIVES AS NOVEL ANTICANCER AGENTS
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The invention provides quinoline derivatives, their manufacture, pharmaceutical compositions containing them, and their use as medicaments. The active compounds of the present invention are useful for the treatment of proliferative neoplastic and nonneoplastic diseases.
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Page/Page column 56; 57
(2014/10/03)
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- Enantioselective Mannich reaction of β-keto esters with aromatic and aliphatic imines using a cooperatively assisted bifunctional catalyst
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An efficient urea-enhanced thiourea catalyst enables the enantioselective Mannich reaction between β-keto esters and N-Boc-protected imines under mild conditions and minimal catalyst loading (1-3 mol %). Aliphatic and aromatic substituents are tolerated on both reaction partners, affording the products in good enantiomeric purity. The corresponding β-amino ketones can readily be accessed via decarboxylation without loss of enantiomeric purity.
- Neuvonen, Antti J.,Pihko, Petri M.
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supporting information
p. 5152 - 5155
(2015/01/08)
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- TEMPO-catalyzed aerobic oxygenation and nitrogenation of olefins via C=C double-bond cleavage
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A novel TEMPO-catalyzed aerobic oxygenation and nitrogenation of hydrocarbons via C=C double-bond cleavage has been disclosed. The reaction employs molecular oxygen as the terminal oxidant and oxygen-atom source by metal-free catalysis under mild conditions. This method can be used for the preparation of industrially and pharmaceutically important N- and O-containing motifs, directly from simple and readily available hydrocarbons.
- Wang, Teng,Jiao, Ning
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p. 11692 - 11695
(2013/09/02)
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- Tert-BuOK-Catalyzed condensation of ethyl diazoacetate to aldehydes and palladium-catalyzed 1,2-hydrogen migration for the synthesis of β-ketoesters under solvent-free conditions
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A mild and convenient method for the condensation of ethyl diazoacetate (EDA) with aldehydes catalyzed by tert-BuOK under solvent-free conditions was developed. The corresponding α-diazo-β-hydroxy esters were further converted into β-ketoesters through palladium-catalyzed 1,2-hydrogen migration under neat conditions. The two-step transformation exemplifies a simple method for the efficient and green synthesis of β-ketoesters. The Royal Society of Chemistry 2013.
- Chen, Shufeng,Yuan, Fang,Zhao, Haiying,Li, Baoguo
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p. 12616 - 12620
(2013/08/23)
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- INHIBITORS OF HEPATITIS C VIRUS
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A class of compounds that inhibit Hepatitis C Virus (HCV) is disclosed, along with compositions containing the compound, and methods of using the composition for treating individuals infected with HCV.
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Page/Page column 147
(2012/05/19)
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- BENZOFURAN DERIVATIVES FOR THE TREATMENT OF HEPATITS C
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The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds have activity agamst hepatitis C virus (HCV) and may be useful in treating those infected with HCV.
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Page/Page column 21
(2012/01/15)
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- Enantioselective titanium(III)-catalyzed reductive cyclization of ketonitriles
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Reduction, please! The title reaction affords ?-hydroxyketones, a common structural motif in biologically active natural products, in good yields and high enantioselectivities at room temperature. The commercially available ansa-titanocene 1 was found to be an efficient catalyst for this process, which presumably proceeds by addition of a ketyl radical to a nitrile.
- Streuff, Jan,Feurer, Markus,Bichovski, Plamen,Frey, Georg,Gellrich, Urs
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supporting information; experimental part
p. 8661 - 8664
(2012/09/21)
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- Highly diastereoselective and enantioselective synthesis of α-hydroxy β-amino acid derivatives: Lewis base catalyzed hydrosilylation of α-acetoxy β-enamino esters
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By design: A series of α-acetoxy-β-enamino esters 1 were synthesized and then subjected to catalytic asymmetric hydrosilylation. In the presence of a chiral Lewis base catalyst, the reactions proceeded smoothly to provide a wide range of chiral α-acetoxy β-amino acid derivatives in high yields with good diastereoselectivities and enantioselectivities. Copyright
- Jiang, Yan,Chen, Xing,Zheng, Yongsheng,Xue, Zhouyang,Shu, Chang,Yuan, Weicheng,Zhang, Xiaomei
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supporting information; experimental part
p. 7304 - 7307
(2011/09/16)
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- INDAZOLE COMPOUNDS USEFUL AS KETOHEXOKINASE INHIBITORS
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The present invention is directed to substituted indazole compounds, pharmaceutical compositions of these compounds and methods of use thereof. The compounds of the present invention are ketohexokinase (KHK) inhibitors, useful for treating or ameliorating a KHK mediated metabolic disorders and/or diseases such as obesity, Type II diabetes mellitus and Metabolic Syndrome X.
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Page/Page column 51
(2011/11/06)
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- Gold/copper-catalyzed activation of the aci-form of nitromethane in the synthesis of methylene-bridged bis-1,3-dicarbonyl compounds
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Activation of the aci-form of nitromethane using Lewis acids for the attack of carbon nucleophiles was studied. 1,3-Dicarbonyl compounds in the presence of catalytic amounts of AuCl3 or Cu(OTf)2 in nitromethane solvent could be converted into methylene-bridged bis-1,3-dicarbonyl compounds.
- Balamurugan, Rengarajan,Manojveer, Seetharaman
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supporting information; experimental part
p. 11143 - 11145
(2011/11/05)
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- Cross-linked polymers based on 2,3,5,6-tetra-substituted pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (DPP): Synthesis, optical and electronic properties
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A series of 2,3,5,6-tetra-substituted pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (DPP) derivatives carrying thienyl-, 3,4-ethylenedioxy-thienyl- (EDOT-) and 3,4-ethylenedithiathienyl- (EDTT-) substituent groups have been synthesized and electrochemically poly
- Zhang, Kai,Tieke, Bernd,Forgie, John C.,Vilela, Filipe,Parkinson, John A.,Skabara, Peter J.
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scheme or table
p. 6107 - 6114
(2011/09/14)
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- Molybdenum(VI) dichloride dioxide catalyzed synthesis of β-keto esters by C-H insertion of ethyl diazoacetate into aldehydes
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Synthesis of β-keto esters by condensing various aldehydes with ethyl diazoacetate is achieved by using molybdenum(VI) dichloride dioxide. Aromatic, aliphatic, and heterocyclic aldehydes are successfully condensed with ethyl diazoacetate to obtain corresponding β-keto esters in high yields at room temperature.
- Jeyakumar, Kandasamy,Chand, Dillip Kumar
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p. 1685 - 1687
(2008/12/21)
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- DBU-catalyzed condensation of acyldiazomethanes to aldehydes in water and a new approach to ethyl β-hydroxy α-arylacrylates
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DBU-catalyzed condensation of ethyl diazoacetate (EDA) with aldehydes in pure water afforded corresponding β-hydroxy α-diazo carbonyl compounds. The β-hydroxy group of the products was further converted into β-siloxy group. The Rh(II)-catalyzed reaction of the β-aryl β-siloxy α-diazo carbonyl compounds gave 1,2-aryl shift products predominantly. The three-step transformation constitutes an efficient synthesis of ethyl β-hydroxy α-arylacrylates.
- Xiao, Fengping,Liu, Yu,Wang, Jianbo
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p. 1147 - 1149
(2007/10/03)
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- Substitution of acyl for acetyl with N-acylbenzotriazoles catalyzed by samarium triiodide
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Catalyzed by samarium triiodide (SmI3), substitution of acyl with N-acylbenzotriazoles for acetyl in acetoacetic esters and acetylacetone proceeds smoothly under neutral conditions in open air, affording the corresponding β-keto esters and β-diketones in good yields. Copyright Taylor & Francis Group, LLC.
- Zou, Xuefei,Jia, Xiaofei,Wang, Xiaoxia,Xie, Guanqun
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p. 1617 - 1625
(2008/02/01)
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- PYRROLE AND PYRAZOLE DERIVATIVES AS POTENTIATORS OF GLUTAMATE RECEPTORS
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The present invention relates to pyrrole and pyrazole compounds of formula (I) and their pharmaceutically acceptable salts, and further relates to their use in treating schizophrenia, cognitive deficits associated with schizophrenia, Alzheimer's disease, dementia of the Alzheimer's type, mild cognitive impairment, or depression. The compounds act as potentiators on glutamate receptors, in particular AMPA and the GluR family.
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Page/Page column 255
(2008/06/13)
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- Lipid-Lowering Effects of Ethyl 2-Phenacyl-3-aryl-1H-pyrrole-4-carboxylates in Rodents
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A series of substituted 2-phenacyl-3-phenyl-1H-pyrrole-4-carboxylates were prepared from substituted acetophenones in 6 steps. The final condensations between a chloroenal and an aminoketone were carried out under neutral conditions in parallel to yield the series listed below. Selected pyrrole derivatives proved to be potent hypolipidemic agents lowering serum triglyceride concentrations in CF-1 male mice after 14 days of I.P. administration. One agent orally lowered serum cholesterol in Sprague-Dawley male rats at 2 mg/kg/day after 14 days. The agents demonstrated a lowering of mouse serum LDL-cholesterol levels and selected compounds showed an elevation of serum HDL-cholesterol levels. The cholesterol concentrations in the liver were raised while the cholesterol and triglyceride contents of the aorta were significantly lowered by the selected trisubstituted pyrrole.
- Holub, Justin M.,O'Toole-Colin, Kathy,Getzel, Adam,Argenti, Anthony,Evans, Michael A.,Smith, Daniel C.,Dalglish, Gerard A.,Rifat, Shahzad,Wilson, Donna L.,Taylor, Brett M.,Miott, Ulander,et al.
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p. 135 - 157
(2007/10/03)
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- Acid-catalyzed reactions of aromatic aldehydes with ethyl diazoacetate: An investigation on the synthesis of 3-hydroxy-2-arylacrylic acid ethyl esters
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Several commercial Lewis acids, including those of the Bronsted type, specifically HBF4·OEt2, are able to catalyze the reaction between aromatic aldehydes and ethyl diazoacetate to produce 3-hydroxy-2-arylacrylic acid ethyl esters and 3-oxo-3-arylpropanoic acid ethyl esters. Reactions catalyzed by the iron Lewis acid [(η5-C 5H5)Fe+(CO)2(THF)]BF 4- (i.e., 1) have the best yields and greatest ratio of 3-hydroxy-2-arylacrylic acid ethyl ester. The product distribution of 1 is not affected in the presence of Proton Sponge, but is dependent on temperature and the nature of the substrate aldehyde, whereas the activity of HBF 4-OEt2 is affected by the presence of Proton Sponge and is reactive at temperatures as low as -78 °C. Consequently, both 1 and HBF4·OEt2 are valuable catalysts in producing important 3-hydroxy-2-arylacrylic acid ethyl esters as precursors to biologically active compounds.
- Dudley, Matthew E.,Morshed, Monzur,Brennan, Courtney L.,Islam, M. Shahidul,Ahmad, M. Syarhabil,Atuu, Mary-Rose,Branstetter, Bryan,Hossain, M. Mahmun
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p. 7599 - 7608
(2007/10/03)
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- Synthesis and cytotoxicity of substituted ethyl 2-phenacyl-3-phenylpyrrole-4-carboxylates
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The substituted ethyl-2-phenacyl-3-phenylpyrrole-4-carboxylates were synthesized by a condensation of a beta-chloroenal and an alpha-aminoketone under neutral conditions. They proved to be potent cytotoxic agents against the growth of murine L1210 and P38
- Evans, Michael A.,Smith, Daniel C.,Holub, Justin M.,Argenti, Anthony,Hoff, Mafoloe,Dalglish, Gerard A.,Wilson, Donna L.,Taylor, Brett M.,Berkowitz, Joshua D.,Burnham, Bruce S.,Krumpe, Keith,Gupton, John T.,Scarlett, Tanya C.,Durham Jr., Richard W.,Hall, Iris H.
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p. 181 - 190
(2007/10/03)
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- Hypoglycemic thiazolidinediones and intermediates
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Optically pure thiazolidinedione alcohols and ethers, and synthetic intermediates for preparing said alcohols and ethers. These compounds have utility as hypoglycemic and hypocholesterolemic agents.
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- Pharmaceutical xanthene compounds
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A pharmaceutical compound of the formula: STR1 in which A is carboxy, tetrazolyl, --SO2 H, --SO3 H, --OSO3 H, --CONHOH, or --P(OH)OR', --PO(OH)OR', --OPO(OH)OR' B is a bond, C1-6 alkylene or C2-6 alke
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- Substituted benzyl pyrimidines
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Compounds of the formula: STR1 in which R1 is lower alkoxy, R2 is bromine or lower alkoxy, and R3 is aryl, heteroaryl or a group --Q--R30, wherein Q is ethylene, vinylene or ethynylene and R30 is aryl, heteroaryl, lower alkoxycarbonyl or carbamoyl; hydrolyzable esters of carboxylic acids of formula I; and pharmaceutically acceptable salts of these compounds are useful for treating infectious diseases.
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