- PQQ-dependent Dehydrogenase Enables One-pot Bi-enzymatic Enantio-convergent Biocatalytic Amination of Racemic sec-Allylic Alcohols
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The asymmetric amination of secondary racemic allylic alcohols bears several challenges like the reactivity of the bi-functional substrate/product as well as of the α,β-unsaturated ketone intermediate in an oxidation-reductive amination sequence. Heading for a biocatalytic amination cascade with a minimal number of enzymes, an oxidation step was implemented relying on a single PQQ-dependent dehydrogenase with low enantioselectivity. This enzyme allowed the oxidation of both enantiomers at the expense of iron(III) as oxidant. The stereoselective amination of the α,β-unsaturated ketone intermediate was achieved with transaminases using 1-phenylethylamine as formal reducing agent as well as nitrogen source. Choosing an appropriate transaminase, either the (R)- or (S)-enantiomer was obtained in optically pure form (>98 % ee). The enantio-convergent amination of the racemic allylic alcohols to one single allylic amine enantiomer was achieved in one pot in a sequential cascade.
- Gandomkar, Somayyeh,Rocha, Raquel,Sorgenfrei, Frieda A.,Montero, Lía Martínez,Fuchs, Michael,Kroutil, Wolfgang
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p. 1290 - 1293
(2020/12/23)
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- 8-Hydroxyquinolin-2(1H)-one analogues as potential β2-agonists: Design, synthesis and activity study
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β2-Agonists that bind to plasmalemmal β2-adrenoceptors causing cAMP accumulation are widely used as bronchodilators in chronic respiratory diseases. Here, we designed and synthesized a group of 8-hydroxyquinolin-2(1H)-one analogues and studied their β2-agonistic activities with a cellular cAMP assay. Compounds B05 and C08 were identified as potent (EC50 2-agonists among the compounds tested. They behaved as partial β2-agonists in non-overexpressed HEK293 cells, and possessed rapid smooth muscle relaxant actions and long duration of action in isolated guinea pig tracheal strip preparations. In summary, B05 and C08 are β2-agonists with potential applicability in chronic respiratory diseases.
- Xing, Gang,Zhi, Zhengxing,Yi, Ce,Zou, Jitian,Jing, Xuefeng,Yiu-Ho Woo, Anthony,Lin, Bin,Pan, Li,Zhang, Yuyang,Cheng, Maosheng
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-
- Design, synthesis, and molecular docking study of novel quinoline-based bis-chalcones as potential antitumor agents
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A novel series of quinoline-based symmetrical and unsymmetrical bis-chalcones was synthesized via a Claisen–Schmidt condensation reaction between 3-formyl-quinoline/quinolone derivatives with acetone or arylidene acetones, respectively, by using KOH/MeOH/H2O as a reaction medium. Twelve of the obtained compounds were evaluated for their in vitro cytotoxic activity against 60 different human cancer cell lines according to the National Cancer Institute protocol. Among the screened compounds, the symmetrical N-butyl bis-quinolinyl-chalcone 14g and the unsymmetrical quinolinyl-bis-chalcone 17o bearing a 7-chloro-substitution on the N-benzylquinoline moiety and 4-hydroxy-3-methoxy substituent on the phenyl ring, respectively, exhibited the highest overall cytotoxicity against the evaluated cell lines with a GI50 range of 0.16–5.45 μM, with HCT-116 (GI50 = 0.16) and HT29 (GI50 = 0.42 μM) (colon cancer) representing best-case scenarios. Notably, several GI50 values for these compounds were lower than those of the reference drugs doxorubicin and 5-FU. Docking studies performed on selected derivatives yielded very good binding energies in the active site of proteins that participate in key carcinogenic pathways.
- Insuasty, Daniel,García, Stephanie,Abonia, Rodrigo,Insuasty, Braulio,Quiroga, Jairo,Nogueras, Manuel,Cobo, Justo,Borosky, Gabriela L.,Laali, Kenneth K.
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- Organocatalytic diastereo- And enantioselective oxa-hetero-Diels-Alder reactions of enones with aryl trifluoromethyl ketones for the synthesis of trifluoromethyl-substituted tetrahydropyrans
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Tetrahydropyran derivatives are found in bioactives, and introduction of the trifluoromethyl group into molecules often improves biofunctions. Here we report diastereo- and enantioselective oxa-hetero-Diels-Alder reactions catalyzed by amine-based catalyst systems that afford trifluoromethyl-substituted tetrahydropyranones. Catalyst systems and conditions suitable for the reactions to provide the desired diastereomer products with high enantioselectivities were identified, and various trifluoromethyl-substituted tetrahydropyranones were synthesized with high diastereo- and enantioselectivities. Mechanistic investigation suggested that the reactions involve a [4 + 2] cycloaddition pathway, in which the enamine of the enone acts as the diene and the ketone carbonyl group of the aryl trifluoromethyl ketone acts as the dienophile. In this study, tetrahydropyran derivatives with the desired stereochemistry that are difficult to synthesize by previously reported methods were concisely obtained, and the range of tetrahydropyran derivatives that can be synthesized was expanded. This journal is
- Pasha, Maira,Tanaka, Fujie
-
supporting information
p. 9242 - 9250
(2021/11/16)
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- Overcoming Kinetic and Thermodynamic Challenges of Classic Cope Rearrangements
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Systematic evaluation of 1,5-dienes bearing 3,3-electron-withdrawing groups and 4-methylation results in the discovery of a Cope rearrangement for Meldrum's acid-containing substrates that have unexpectedly favorable kinetic and thermodynamic profiles. The protocol is quite general due to a concise and convergent synthesis from abundant starting materials. Furthermore, products with an embedded Meldrum's acid moiety are prepared, which, in turn, can yield complex amides under neutral conditions. We have now expanded the scope of the reductive Cope rearrangement, which, via chemoselective reduction, can promote thermodynamically unfavorable [3,3] sigmatropic rearrangements of 3,3-dicyano-1,5-dienes to form reduced Cope rearrangement products. The Cope rearrangement is found to be stereospecific and can yield enantioenriched building blocks when chiral, nonracemic 1,3-disubstituted allylic electrophiles are utilized. We expand further the use of Cope rearrangements for the synthesis of highly valuable building blocks for complex- and drug-like molecular synthesis.
- Fereyduni, Ehsan,Lahtigui, Ouidad,Sanders, Jacob N.,Tomiczek, Breanna M.,Mannchen, Michael D.,Yu, Roland A.,Houk,Grenning, Alexander J.
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p. 2632 - 2643
(2021/02/05)
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- NOVEL SMALL MOLECULES THAT BIND AND/OR MODULATE DIFFERENTFORMS OF TAU OLIGOMERS
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The present invention relates to novel small molecules of Formulas I, II, III, Ilia, Illb, and IV and pharmaceutically acceptable salts thereof, as well as the preparation and the use thereof.
- -
-
Page/Page column 34; 35
(2020/11/03)
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- Design, synthesis and biological evaluation of novel diaryl pyrazole derivatives as anticancer agents
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Cancer is one of the major causes of mortality all around the world. Globally, nearly 1 in 6 deaths is due to cancer. Researchers are trying to synthesize new anticancer agents. Previous studies demonstrated that some pyrazole derivatives could be considered as potential anticancer agents. Herein, ten novel derivatives of 1,5-diarylpyrazole were synthesized in four step reactions and cytotoxic activity was investigated by MTT cell viability assay. All of the compounds were characterized by1H NMR and13C NMR and their purity was confirmed by elemental analysis. The cytotoxicity was determined against three cancerous cell lines (HT-29, U87MG and MDA-MB 468) and AGO1522 as a normal cell line. Compound 5a showed the best cytotoxic activity on cancerous cell lines in comparison to paclitaxel. Annexin V/ PI staining assay also showed that compounds 5a and 5i would lead to significant apoptosis induction in MDA-MB 486 cell line.
- Nourmahammadi, Jalal,Moghadam, Ebrahim Saeedian,Shahsavari, Zahra,Amini, Mohsen
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p. 216 - 223
(2020/02/29)
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- A bioinspired microreactor with interfacial regulation for maximizing selectivity in a catalytic reaction
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We report a bioinspired emulsion microreactor composed of an electrical double layer to mimic the functions of cell membranes. This "artificial cell"can modulate the phase-oriented transport of reagents at the oil-liquid interface via the electrical double layer, affording a powerful tool to optimize the selectivity in a catalytic reaction. This journal is
- Han, Chenhui,Li, Xin-Hao,Waclawik, Eric R.,Xu, Haolan,Xu, Jingsan
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supporting information
p. 8059 - 8062
(2020/09/09)
-
- THIAZOLE DERIVATIVES AS PROTEIN SECRETION INHIBITORS
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Provided herein are secretion inhibitors, such as inhibitors of Sec61, methods for their preparation, related pharmaceutical compositions, and methods for using the same, wherein the compound has a structure of Formula (I), (II), or (III).
- -
-
Paragraph 0260; 0330
(2020/09/12)
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- Boosting multiple photo-assisted and temperature controlled reactions with a single redox-switchable catalyst: Solvents as internal substrates and reducing agent
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An alternative and economically viable process for the synthesis of β-aryl enals, enones and the aryl amines has been developed by partial oxidation of ethanol, isopropanol and N, N-dimethyl formamide (DMF). The formation of β-aryl enals, enones and the aryl amines was catalyzed by a mixed metal oxides layer of cobalt and chromium supported on halloysite nanotubes, designated as CoCr2O4-HNT. The C[sbnd]C and C[sbnd]N bond formation reactions were found to be influenced by temperature and the nature of base. The condensation of aldehyde with in situ generated acetaldehyde by ethanol oxidation forming β-aryl enals occurred selectively at 120 °C. The partial oxidation of isopropanol to acetone and its condensation with aldehydes forming β-aryl enones occurred at room temperature. Increase in temperature caused the liberation of hydrogen gas from isopropanol and allowed the reversible reduction of aldehydes to alcohols. Increase in temperature in isopropanol and increase in base concentration in ethanol causes the selective reduction of aldehydes to alcohols. Besides being active for the Claisen-Schmidt type of reactions and the aryl halides amination process, the synthesized catalyst was also found to be highly active for the photocatalytic oxidation of benzyl alcohols in absence of any external oxidizing agent. The positive holes (h+) generated at the Co(II) site as evident from EPR analysis was considered to be responsible for high photocatalytic activity of the material reducing the recombination rate of holes and electrons (e?). Density Functional Theory calculations were performed to understand the mechanism of ethanol oxidation to acetaldehyde.
- Bania, Kusum K.,Baruah, Manash J.,Bhattacharyya, Pradip K.,Das, Biraj,Karunakar, Galla V.,Roy, Subhasish,Saikia, Lakshi,Saikia, Pinku,Sharma, Mukesh
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p. 104 - 121
(2020/06/01)
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- The construction of novel and efficient hafnium catalysts using naturally existing tannic acid for Meerwein-Ponndorf-Verley reduction
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The conversion of carbonyl compounds into alcohols or their derivatives via the catalytic transfer hydrogenation (CTH) process known as Meerwein-Ponndorf-Verley reduction is an important reaction in the reaction chain involved in biomass transformation. The rational design of efficient catalysts using natural and renewable materials is critical for decreasing the catalyst cost and for the sustainable supply of raw materials during catalyst preparation. In this study, a novel hafnium-based catalyst was constructed using naturally existing tannic acid as the ligand. The prepared hafnium-tannic acid (Hf-TA) catalyst was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and thermogravimetry (TG). Hf-TA was applied in the conversion of furfuraldehyde (FD) to furfuryl alcohol (FA) using isopropanol (2-PrOH) as both the reaction solvent and the hydrogen source. Both preparation conditions and the effects of the reaction parameters on the performance of the catalyst were studied. Under the relatively mild reaction conditions of 70 °C and 3 h, FD (1 mmol) could be converted into FA with a high yield of 99.0%. In addition, the Hf-TA catalyst could be reused at least ten times without a notable decrease in activity and selectivity, indicating its excellent stability. It was proved that Hf-TA could also catalyze the conversion of various carbonyl compounds with different structures. The high efficiency, natural occurrence of tannic acid, and facile preparation process make Hf-TA a potential catalyst for applications in the biomass conversion field.
- Deng, Lijuan,Hao, Jianxiu,He, Runxia,Li, Na,Liu, Quansheng,Wang, Xiaolu,Zhao, Hongye,Zhi, Keduan,Zhou, Huacong
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p. 6944 - 6952
(2020/03/03)
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- Dehydrozingerone derivative and preparation method and application thereof
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The invention provides a dehydrozingerone derivative as shown in the description. R-R are each independently selected from hydrogen or halogen or a nitro group or an alkyl group or a substitutedalkoxy group or an alkoxy group or a hydroxyl group; the substituent in the substituted alkoxy group is selected from one or multiple of halogen, a nitro group and a hydroxyl group; R and R areeach independently selected from hydrogen or halogen or nitrogen-containing heterocycle; R is selected from an alkyl group or an alkoxy group or a substituted alkoxy group; the substituent in thesubstituted alkyl group is selected from one or multiple of halogen, a nitro group and a hydroxyl group; X is selected from a hetero atom or a hydroxylamine group. The dehydrozingerone derivative hasbroad-spectrum activity against plant pathogenic fungi and bacteria, and has certain nematicidal activity, and is a lead compound with the broad biological activity.
- -
-
Paragraph 0084-0087; 0088; 0098
(2019/11/20)
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- Silica gel-mediated self-aldol reactions of highly volatile aldehydes under organic solvent-free conditions without reflux condenser
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Silica gel-mediated self-aldol reactions were catalyzed by piperidine to give the corresponding α,β-conjugated aldehydes in good yields. The aldol reactions of 4-nitro-, 4-trifluoromethyl-, and 4-chlorobenzaldehydes with acetone afforded the corresponding aldol products. Highly volatile aldehydes and acetone could be employed even without a reflux condenser for these reactions. Silica gel could be recycled five times without any significant decrease of the yields of the products.
- Tanemura, Kiyoshi
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p. 1924 - 1928
(2019/06/24)
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- Fe3O4?l-Proline/Pd nanocomposite for one-pot tandem catalytic synthesis of (±)-warfarin from benzyl alcohol: Synergistic action of organocatalyst and transition metal catalyst
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One-pot synthesis of (±)-warfarin, an anticoagulant, has been achieved from benzyl alcohol in a 'green way' by using a multicomponent catalyst. For the purpose, l-proline capped Fe3O4 nanoparticles (Fe3O4?l-proline NPs) were synthesized and metallic palladium was loaded on its surface (Fe3O4?l-proline/Pd NCs). The morphology, particle size and shape were studied by using FESEM and TEM analysis. The Pd present on the surface was responsible for oxidation of benzyl alcohol and its derivatives to the corresponding aldehyde in situ. This in turn, condensed with acetone to form the aldol condensation product, benzylideneacetone, at 70 °C due to the presence of the l-proline organocatalyst on the surface of Fe3O4 NPs. Later, 4-hydroxycoumarin was introduced to condense with in situ generated benzylideneacetone by a Michael addition to form the target product (±)-warfarin. It was established that benzyl alcohol can be converted into the final product, (±)-warfarin, with an overall 35% yield within 5 days in a single-pot process. This process requires a rise in temperature in stages to a maximum of 100 °C and 1 atm pressure of dioxygen gas. An important aspect of the developed process is the avoidance of loss of costly Pd by leaching and catalyst recovery by the use of a magnetic field. The use of a solvent like PEG-400 makes the process green in a true sense. The interaction of l-proline with Fe3O4 NPs and the presence of Pd on the surface were confirmed by the FTIR and XRD patterns, respectively. The present study hereby suggests a combined 3-step mechanism for the production of the target product warfarin. Pilot-scale one-pot production of (±)-warfarin was carried out and a flow diagram with various unit processes is presented.
- Tomer, Sanjiv O.,Soni, Hemant P.
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p. 6517 - 6531
(2019/11/20)
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- Construction of Multiple-Substituted Chiral Cyclohexanes through Hydrogenative Desymmetrization of 2,2,5-Trisubstituted 1,3-Cyclohexanediones
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The construction of chiral multiple-substituted cyclohexanes motifs is a challenging topic in organic synthesis. By the combination of desymmetrization and remote stereocontrol, a ruthenium-catalyzed transfer hydrogenative desymmetrization of 2,2,5-trisubstituted 1,3-cyclohexanediones has been successfully developed for the construction of chiral multiple-substituted cyclohexanes with high enantioselectivity and diastereoselectivity. When an ester group was introduced to the two-position, a hydrogenative desymmetrization/transesterification cascade occurred, affording the bicyclic lactones bearing three stereocenters, including two discrete stereocenters and one quaternary stereogenic center, with high enantioselectivity. The products are the multiple-substituted chiral cyclohexanes bearing the hydroxyl and carbonyl functional groups, which provide a new opportunity for further precise elaboration.
- Yu, Chang-Bin,Song, Bo,Chen, Mu-Wang,Shen, Hong-Qiang,Zhou, Yong-Gui
-
supporting information
p. 9401 - 9404
(2019/11/28)
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- Encapsulating mesoporous metal nanoparticles: Towards a highly active and stable nanoreactor for oxidative coupling reactions in water
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We design and prepare a highly active and stable nanoreactor via encapsulating various mesoporous metal nanoparticles with an amphiphilic hollow shell, which presents excellent performance in oxidative coupling reactions in water for efficient production of α,β-unsaturated ketones.
- Zou, Houbing,Dai, Jinyu,Wang, Runwei
-
supporting information
p. 5898 - 5901
(2019/05/27)
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- Mild Chemoenzymatic Oxidation of Allylic sec-Alcohols. Application to Biocatalytic Stereoselective Redox Isomerizations
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The design of catalytic oxidative methodologies in aqueous medium under mild reaction conditions and using molecular oxygen as final electron acceptor represents a suitable alternative to the traditional oxidative transformations. These methods are especially relevant if other functionalities that can be oxidized are present within the same molecule, as in the case of allylic alcohols. Herein we apply a simple chemoenzymatic system composed of the laccase from Trametes versicolor and 2,2,6,6-tetramethylpiperidinyloxy radical (TEMPO) to oxidize a series of racemic allylic sec-alcohols into the corresponding α,β-unsaturated ketones. Afterward, these compounds react with different commercially available ene-reductases to afford the corresponding saturated ketones. Remarkably, in the case of trisubstituted alkenes, the bioreduction reaction occurred with high stereoselectivity. Overall, a bienzymatic one-pot two-step sequential strategy has been described with respect to the synthesis of saturated ketones starting from racemic allylic alcohols, thus resembling the metal-catalyzed redox isomerizations of these derivatives that have been previously reported in the literature.
- Martínez-Montero, Lía,Gotor, Vicente,Gotor-Fernández, Vicente,Lavandera, Iván
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p. 2413 - 2419
(2018/03/13)
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- Discovery of novel 5-methyl-1H-pyrazole derivatives as potential antiprostate cancer agents: Design, synthesis, molecular modeling, and biological evaluation
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Androgen receptor (AR) signaling functions as a core driving force for the progression of prostate cancer (PCa), and AR has been proved to be an effective therapeutic target even for castration-resistant prostate cancer (CRPC). Herein, structural modification via a fragments splicing strategy was performed based on two lead compounds T3 and 10e, leading to the discovery of a series of 5-methyl-1H-pyrazole derivatives. AR reporter gene assay revealed compounds A13 and A14 as potent AR antagonists. Some of the compounds in this series inhibited growth of PCa LNCaP cells more efficiently than enzalutamide. A13 and A14 also showed improved metabolic stability compared with 10e in human liver microsomes.
- Zhang, Daoguang,Asnake, Solomon,Zhang, Jingya,Olsson, Per-Erik,Zhao, Guisen
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p. 1113 - 1124
(2018/03/05)
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- Evaluation of sulphonamide derivatives acting as inhibitors of human carbonic anhydrase isoforms I, II and Mycobacterium tuberculosis β-class enzyme Rv3273
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A series of novel sulphonamide derivatives was obtained from sulphanilamide which was N4-alkylated with ethyl bromoacetate followed by reaction with hydrazine hydrate. The hydrazide obtained was further reacted with various aromatic aldehydes. The novel sulphonamides were characterised by infrared, mass spectrometry, 1H- and 13C-NMR and purity was determined by high-performance liquid chromatography (HPLC). Human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I and II and Mycobacterium tuberculosis β-CA encoded by the gene Rv3273 (mtCA 3) inhibition activity was investigated with the synthesised compounds which showed promising inhibition. The KIs were in the range of 54.6 nM–1.8 μM against hCA I, in the range of 32.1 nM–5.5 μM against hCA II and of 127 nM–2.12 μM against mtCA 3.
- Wani, Tanvi V.,Bua, Silvia,Khude, Pravin S.,Chowdhary, Abdul H.,Supuran, Claudiu T.,Toraskar, Mrunmayee P.
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p. 962 - 971
(2018/05/29)
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- Cascade Reaction by Chemo- and Biocatalytic Approaches to Obtain Chiral Hydroxy Ketones and anti 1,3-Diols
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A chemo- and biocatalytic cascade approach was applied for the stereoselective synthesis of hydroxy ketones and the corresponding 1,3-diols. A new class of tridentate N,N,O ligands was used with copper(II) complexes for the asymmetric β-borylation of α,β-unsaturated compounds. The complex containing ligand L5 emerged as the best performer, and it gave the organoborane derivatives with good ee values. The corresponding keto–alcohol compounds were then bioreduced by yeasts. The biotransformation set up with Rhodotorula rubra allowed (R)-keto–alcohols and (S,S)-diols to be obtained with up to 99 % ee and up to 99 % de in favor of the anti enantiomers.
- Gandolfi, Raffaella,Facchetti, Giorgio,Christodoulou, Michael S.,Fusè, Marco,Meneghetti, Fiorella,Rimoldi, Isabella
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p. 393 - 400
(2018/06/04)
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- Rh(III)-Catalyzed Enaminone-Directed Alkenyl C-H Activation for the Synthesis of Salicylaldehydes
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A Rh(III)-catalyzed enaminone-directed alkenyl C-H coupling with alkynes for the synthesis of salicylaldehyde derivatives is reported. This represents a unique example of benzene ring framework formation through a transition-metal-catalyzed, directed C-H activation strategy. The two incorporated reactive functionalities, aldehyde and hydroxy groups, provide convenient synthetic handles for further structural elaboration.
- Qi, Bing,Guo, Shan,Zhang, Wenjing,Yu, Xiaolong,Song, Chao,Zhu, Jin
-
supporting information
p. 3996 - 3999
(2018/07/15)
-
- Palladium-Catalyzed Cleavage of α-Allenylic Aryl Ether toward Pyrazolemethylene-Substituted Phosphinyl Allenes and Their Transformations via Alkenyl C-P(O) Cleavage
-
A palladium-catalyzed two-component coupling of allenylphosphine oxides with conjugated N-tosylhydrazones is revealed. For the first time, the cleavage of α-allenylic aryl ether toward pyrazolemethylene-substituted phosphinyl allenes enabled facile synthesis of combined motifs with pyrazole and allene. Moreover, the obtained adducts could be easily transformed to potential bioactive multifunctionalized phosphinates via a novel alkenyl C-P(O) cleavage.
- Zhu, Jie,Mao, Mao,Ji, Huan-Jing,Xu, Jiang-Yan,Wu, Lei
-
supporting information
p. 1946 - 1949
(2017/04/28)
-
- Discovery of curcumin inspired sulfonamide derivatives as a new class of carbonic anhydrase isoforms I, II, IX, and XII inhibitors
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A series of curcumin inspired sulfonamide derivatives was prepared from various chalcones and 4-sulfamoyl benzaldehyde via Claisen–Schmidt condensation. All new compounds were assayed as inhibitors of four human isoforms of the metalloenzyme carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I, II, IX and XII. Interesting inhibitory activities were observed against all these isoforms. hCA I, an isoform involved in several eye diseases was inhibited moderately with KIs in the range of 191.8–904.2 nM, hCA II, an antiglaucoma drug target was highly inhibited by the new sulfonamides, with KIs in the range of 0.75–8.8 nM. hCA IX, a tumor-associated isoform involved in cancer progression and metastatic spread was potently inhibited by the new sulfonamides, with KIs in the range of 2.3–87.3 nM, whereas hCA XII, and antiglaucoma and anticancer drug target, was inhibited with KIs in the range of 6.1–71.8 nM. It is noteworthy that one of the new compounds, 5d, was found to be almost 9 times more selective against hCA II (KI = 0.89 nM) over hCA IX and hCA XII, whereas 5e was 3 and 70 times more selective against hCA II (KI = 0.75 nM) over hCA IX and hCA XII, respectively.
- Ramya, P. V. Sri,Angapelly, Srinivas,Angeli, Andrea,Digwal, Chander Singh,Arifuddin, Mohammed,Babu, Bathini Nagendra,Supuran, Claudiu T.,Kamal, Ahmed
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p. 1274 - 1281
(2017/10/09)
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- Method for preparing alpha and beta-unsaturated ketone
-
The invention provides a method for preparing alpha and beta-unsaturated ketone. The method includes that L-proline is used as a catalyst, secondary amine is used as a cocatalyst, and the alpha and beta-unsaturated ketone can be directly synthesized in alcohol or ketone solution by means of aldol condensation under neutral conditions at one step. Compared with the traditional method, the method has the advantages that raw materials are easily available, the method is low in cost and is environmental friendly, reaction conditions are mild, solvents are clean and environmental friendly, equipment can be protected against corrosion under the neutral conditions, the catalyst is high in acid resistance, and the method is applicable to industrial production.
- -
-
Paragraph 0035; 0036
(2016/10/31)
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- Discovery of New Monocarbonyl Ligustrazine-Curcumin Hybrids for Intervention of Drug-Sensitive and Drug-Resistant Lung Cancer
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The elevation of oxidative stress preferentially in cancer cells by inhibiting thioredoxin reductase (TrxR) and/or enhancing reactive oxygen species (ROS) production has emerged as an effective strategy for selectively targeting cancer cells. In this study, we designed and synthesized 21 ligustrazine-curcumin hybrids (10a-u). Biological evaluation indicated that the most active compound 10d significantly inhibited the proliferation of drug-sensitive (A549, SPC-A-1, LTEP-G-2) and drug-resistant (A549/DDP) lung cancer cells but had little effect on nontumor lung epithelial-like cells (HBE). Furthermore, 10d suppressed the TrxR/Trx system and promoted intracellular ROS accumulation and cancer cell apoptosis. Additionally, 10d inhibited the NF-κB, AKT, and ERK signaling, P-gp-mediated efflux of rhodamine 123, P-gp ATPase activity, and P-gp expression in A549/DDP cells. Finally, 10d repressed the growth of implanted human drug-resistant lung cancer in mice. Together, 10d acts a novel TrxR inhibitor and may be a promising candidate for intervention of lung cancer.
- Ai, Yong,Zhu, Bin,Ren, Caiping,Kang, Fenghua,Li, Jinlong,Huang, Zhangjian,Lai, Yisheng,Peng, Sixun,Ding, Ke,Tian, Jide,Zhang, Yihua
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p. 1747 - 1760
(2016/03/25)
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- Enzyme-catalyzed domino reaction: Efficient construction of spirocyclic oxindole skeleton using porcine pepsin
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Pepsin from porcine gastric mucosa was used as a sustainable and environmentally friendly biocatalyst in the domino Knoevenagel/Michael/Michael reaction for the synthesis of spirooxindole derivatives in methanol. A wide range of isatins and α,β-unsaturated ketones reacting with malononitrile provided the corresponding products in yields of up to 99% with diastereoselectivities of up to >99:1 dr. This pepsin-catalyzed domino reaction provided a novel case of enzyme catalytic promiscuity.
- He, Yan-Hong,He, Tao,Guo, Jun-Tao,Li, Rui,Xiang, Yang,Yang, Da-Cheng,Guan, Zhi
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p. 2239 - 2248
(2016/04/26)
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- Synthesis and neuroprotective evaluation of (E)-3,4-dihydroxystyryl p-substituted-phenethyl ketone derivatives against inflammatory and oxidative injury
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(E)-3,4-dihydroxystyryl p-substituted-phenethyl ketones and their 3,4-diacetylated derivatives were synthesized and examined their neuroprotective activities to further study the effect of p-substituents on the aromatic ring. The results revealed that steric hindrance effect of p-substituents has impact on neuroprotective activities against inflammatory and oxidative injury. Introduction of the bulkier groups are more beneficial to improve the neuroprotective activities than smaller groups. Compounds (4–5h, 4–5i and 4–5e) with p-substituted trifluoromethyl, isopropyl and t-butyl groups exhibited the best effects among all the target compounds.
- Cheng, Can,Ning, Xianling,Luo, Yongming,Tian, Chao,Wang, Xiaowei,Guo, Ying,Liu, Junyi,Zhang, Zhili
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p. 1678 - 1685
(2016/07/30)
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- A multicomponent pathway-inspired regioselective synthesis of 2,3,4-trisubstituted 1H-pyrroles via [3+2] cycloaddition reaction
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A copper catalyzed regioselective synthesis of 2,3,4-trisubstituted 1H-pyrroles using a novel three-component coupled domino reaction of aldehydes, ketones and alkyl isocyanoacetates is reported. This transformation proceeds through the formation of a chalcone followed by a [3+2] cycloaddition reaction to obtain α-cuprioisocyanide, a cyclic organocopper intermediate, which on copper-hydrogen exchange followed by oxidation exclusively offers 2,3,4-trisubstituted 1H-pyrrole.
- Kalmode, Hanuman P.,Vadagaonkar, Kamlesh S.,Murugan, Kaliyappan,Chaskar, Atul C.
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p. 4631 - 4639
(2015/06/16)
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- Synthesis and antiproliferativeactivity of new vinca alkaloids containing an α,β-unsaturated aromatic side chain
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A new series of vinca-alkaloids derivatives containing various α,β-unsaturated aromatic side chains was synthesized. Four new vinca-alkaloids derivatives showed selective cytotoxicities against KB tumor cell lines with IC50 value below 0.1 μM, thus comparable with vinblastine.
- Ngo, Quoc Anh,Nguyen, Le Anh,Vo, Ngoc Binh,Nguyen, Thuy Hang,Roussi, Fanny,Nguyen, The Hung,Nguyen, Van Tuyen
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p. 5597 - 5600
(2015/11/17)
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- Acid-Base Pairs in Lewis Acidic Zeolites Promote Direct Aldol Reactions by Soft Enolization
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Hf-, Sn-, and Zr-Beta zeolites catalyze the cross-aldol condensation of aromatic aldehydes with acetone under mild reaction conditions with near quantitative yields. NMR studies with isotopically labeled molecules confirm that acid-base pairs in the Si-O-M framework ensemble promote soft enolization through α-proton abstraction. The Lewis acidic zeolites maintain activity in the presence of water and, unlike traditional base catalysts, in acidic solutions.
- Lewis, Jennifer D.,Van De Vyver, Stijn,Romn-Leshkov, Yuriy
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supporting information
p. 9835 - 9838
(2015/08/19)
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- Synthesis of Polysubstituted Pyridines via a One-Pot Metal-Free Strategy
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An efficient strategy for the one-pot synthesis of polysubstituted pyridines via a cascade reaction from aldehydes, phosphorus ylides, and propargyl azide is reported. The reaction sequence involves a Wittig reaction, a Staudinger reaction, an aza-Wittig reaction, a 6π-3-azatriene electrocyclization, and a 1,3-H shift. This protocol provides quick access to the polysubstituted pyridines from readily available substrates in good to excellent yields.
- Wei, Hongbo,Li, Yun,Xiao, Ke,Cheng, Bin,Wang, Huifei,Hu, Lin,Zhai, Hongbin
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supporting information
p. 5974 - 5977
(2016/01/09)
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- Graphene based material as a base catalyst for solvent free Aldol condensation and Knoevenagel reaction at room temperature
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Graphene oxide (GO) acts as a highly active heterogeneous base catalyst for a wide variety of reactions. Here we have described the catalytic activities of GO in the condensation reaction of various substituted benzaldehydes with acetophenone (aldol condensation) and with active methylene compound malononitrile (Knoevenagel reaction) at room temperature under solvent free condition. GO is characterized by powder X-ray diffraction (XRD), UV-visible spectra, Fourier transform infrared spectroscopy (FT-IR) and AFM. The experimental results showed that the GO had higher catalytic activity and it can be recycled without significant loss of its activity.
- Islam, Sk Manirul,Roy, Anupam Singha,Dey, Ram Chandra,Paul, Sumantra
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- Carbon quantum dots with photoenhanced hydrogen-bond catalytic activity in aldol condensations
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Carbon quantum dots (CQDs) were synthesized by an electrochemical etching method. The CQDs are well-dispersed with uniform size about 5 nm. FT-IR spectra suggest the presence of many hydroxyl groups on the surface of CQDs. Here, CQDs with diameter approximately 5 nm, directly used as effective heterogeneous nanocatalysts for H-bond catalysis in aldol condensations, show excellent photoenhanced catalytic ability (89% yields when 4-cyanobenzaldehyde is used). It demonstrated that aldol condensation between acetone and aromatic aldehydes resulted in higher yields with visible light irradiation than in the dark, confirming visible light is necessary for good conversion. The H-bond catalytic activities of CQDs can be significantly enhanced with visible light irradiation. The high catalytic activities of CQDs are due to highly efficient electron-accepting capabilities. Repeated catalytic experiments suggest that the CQD catalyst can be easily recycled as a heterogeneous catalyst with a long catalyst life.
- Han, Yuzhi,Huang, Hui,Zhang, Hengchao,Liu, Yang,Han, Xiao,Liu, Ruihua,Li, Haitao,Kang, Zhenhui
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p. 781 - 787
(2014/04/03)
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- Catalytic microwave-promoted direct aldol condensation using resin-bound secondary amine
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A series of polystyrene-supported imino group-bearing catalysts were prepared. A highly efficient combination of recyclable catalysts and microwave irradiation was developed as a green protocol for the direct aldol reaction. Notably, microwaves greatly shorten the reaction times to only 20 min and improve the yield significantly. Catalyst loading was reduced as well. Different aromatic aldehydes as aldol donors were subjected to our catalyst system and afforded the corresponding products in satisfactory yields. Additionally, the polymer-supported catalysts could be recovered by simple filtration and were reusable for at least four times without significant loss of reactivity. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]
- Liao, Fu Xu,Wang, Yu Guang,Zhu, Qing
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supporting information
p. 161 - 169
(2013/12/04)
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- FLAVONE DERIVATIVES AND THEIR PREPARATIVE METHOD AND MEDICAL USE
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Flavone derivatives, preparative method of the derivatives and use thereof as medicaments for treating diabetes. The structure of the derivatives is presented by formula 1: In the structure, R1 and R2, which are identical or not, represent hydrogen atom, halogen, cyano, hydroxyl, trifluoromethyl, thio-methyl, benzyloxy, C1-C8 linear chain or branch chain alkyl, C1-C8 linear chain or branch chain alkoxy. The pharmacological test indicates that the flavone derivatives can significantly increase the glucose consumption of Hep-G2 cell with insulin resistance activity, promote translocation of glucose transporter 4 of skeletal muscle cells (L6GLUT4myc) at different level, and significantly increase glucose intake and utilization by cells. The test proves the fact for the first time that the flavone derivatives can significantly promote translocation of glucose transporter 4 of skeletal muscle cells, and one of the mechanisms for treating diabetes is activating the cell AMPK phosphorylation and phosphorylating the downstream ACC.
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Paragraph 0028
(2013/09/12)
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- Effect of phosphorus amount on the particle size and catalytic performance of heterogeneous nickel(ii) schiff-base complex in aldol condensation reaction
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The organic-inorganic hybrid of citric acid, tetraethoxysilane (TEOS), and triethylphosphate (TEP) doped by a nickel Schiff-base complex was prepared by sol-gel method. The prepared composites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmittance electron microscopy (TEM), scanning tunnelling microscopy (STM), and infrared spectroscopy (IR). In order to determine the phosphorus amount effect on the catalytic activity of the prepared composites, the aldol condensation was used as a model reaction. The results revealed that the composite with 10% phosphorus is a better catalyst in comparison with other composites.
- Eshtiagh-Hosseini, Hossein,Tabari, Taymaz
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p. 1778 - 1791
(2013/11/06)
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- Efficient synthesis of trifluoromethylated cyclopentadienes/fulvenes/ norbornenes from divinyl ketones
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The synthetic methods of trifluoromethylated cyclopentadienes/fulvenes/ norbornenes have been developed using 3-CF3-1,4-dien-3-ols as the synthons, which can be easily prepared by the regiospecific 1,2-addition of the Ruppert-Prakash reagent (TMSCF3) to divinyl ketones. All the reactions are carried out under mild, metal-free conditions to afford the corresponding products in high to excellent yields.
- Liu, Xiao,Xu, Xianxiu,Pan, Ling,Zhang, Qian,Liu, Qun
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supporting information
p. 6703 - 6706
(2013/10/01)
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- Enantioselective [4 + 2] cycloaddition of cyclic N-sulfimines and acyclic enones or ynones: A concise route to sulfamidate-fused 2,6-disubstituted piperidin-4-ones
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A concise route to valuable sulfamate-fused 2,6-disubstituted piperidin-4-ones or 2,3-dihydropyridin-4(1H)-ones in good yield with high diastereo- and enantioselectivity is presented. The combination of chiral primary amine and o-fluorobenzoic acid efficiently promoted an asymmetric [4 + 2] cycloaddition reaction of N-sulfonylimines and enones or ynones. The cycloaddition reaction between cyclic N-sulfonylimines and ynones is first reported.
- Liu, Yong,Kang, Tai-Ran,Liu, Quan-Zhong,Chen, Lian-Mei,Wang, Ya-Chuan,Liu, Jie,Xie, Yong-Mei,Yang, Jin-Liang,He, Long
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p. 6090 - 6093
(2014/01/06)
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- β-Diphenylphosphorylated alkanones and related compounds: Synthesis and structure
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The reactions of diphenyl(diisopropyl)chlorophosphine with arylidene(heteroarylidene)-acetones and 3-benzylidenepentane-2,4-dione in the presence of acetic acid proceed at a high rate at room temperature to afford the corresponding β-diorganylphosphorylated alkanones and alkanediones in high yields. The reaction of diphenylchlorophosphine with 4-methoxybut-3-en-2-one and dibenzylideneacetone carried out under similar conditions at the equimolar reagent ratio can serve as a convenient method for the synthesis of unique β-diphenylphosphorylalkenones. The structures of compounds obtained were established by IR, Raman, and NMR spectroscopy and X-ray diffraction.
- Goryunov,Bodrin,Goryunova,Nelyubina,Petrovskii,Strelkova,Peregudov,Matveeva,Pasechnik,Matveev,Nifant'Ev
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p. 780 - 791
(2014/01/23)
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- Synthesis of β-sulfanyl ketones via a tandem rearrangement-conjugate addition reaction catalyzed by a Re(V)-oxo complex
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A method for synthesizing β-sulfanyl ketones via a tandem rearrangement and conjugate addition reaction has been developed. This methodology provides access to a range of β-sulfanyl ketones through the rearrangement of propargyl alcohols to the corresponding enones followed by the conjugate addition of unactivated thiols. The one-pot, tandem transformation is catalyzed by ReOCl3(OPPh3)(S(CH3)2) affording aryl and alkyl β-sulfanyl ketones in good to excellent yield.
- Garst, Alyson E.,Badiceanu, Alexandra D.,Nolin, Kristine A.
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supporting information
p. 459 - 461
(2013/02/23)
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- Cu(OAc)2/TFA-promoted formal [3 + 3] cycloaddition/oxidation of enamines and enones for synthesis of multisubstituted aromatic amines
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New strategies for the oxidative cycloaddition of enones with enamines are developed. These cycloaddition reactions directly afford substituted aromatic amines, which are important in organic chemistry, in moderate to good yield. Cu(OAc)2/TFA is shown to be essential to achieve high reaction efficiency.
- Li, Liang,Zhao, Mi-Na,Ren, Zhi-Hui,Li, Jian-Li,Guan, Zheng-Hui
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supporting information; experimental part
p. 3506 - 3509
(2012/08/08)
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- Asymmetric aldol reaction in a continuous-flow reactor catalyzed by a highly reusable heterogeneous peptide
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A solid-supported peptide-catalyzed continuous-flow (CF) process was developed for asymmetric aldol reactions. The catalyst was readily synthesized and immobilized by solid-phase peptide synthesis (SPPS) on a swellable polymer support in one single step. Ignoring the peptide cleavage from the resin means no work-up, no purification, and no product loss. After thorough optimization of the reaction conditions, synthetically useful β-hydroxyketone products were obtained in high yields and stereoselectivities. It was found that the heterogeneous catalytic reaction is diffusion-controlled under the present conditions; thus, elevation of the pressure is necessary to maximize conversion of the flow process. Besides being simple and efficient, the described method is also rapid and promisingly productive, with short residence times on the catalyst bed. The immobilized peptidic catalyst is highly recyclable, while further advantageous features are the ease of product isolation and the possibility of facile scale-up, furnishing sustainable catalytic methodology.
- Oetvoes, Sandor B.,Mandity, Istvan M.,Fueloep, Ferenc
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p. 179 - 185
(2013/01/14)
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- Novel diarylheptanoids as inhibitors of TNF-α production
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Synthesis and anti-inflammatory activity of novel diarylheptanoids [5-hydroxy-1-phenyl-7-(pyridin-3-yl)-heptan-3-ones and 1-phenyl-7-(pyridin-3-yl) hept-4-en-3-ones] as inhibitors of tumor necrosis factor-α (TNF-α) production is described in the present article. The key reactions involve the formation of a β-hydroxyketone by the reaction of substituted 4-phenyl butan-2-ones with pyridine-3-carboxaldehyde in presence of LDA and the subsequent dehydration of the same to obtain the α,β-unsaturated ketones. Compounds 4i, 5b, 5d, and 5g significantly inhibit lipopolysaccharide (LPS)-induced TNF-α production from human peripheral blood mononuclear cells in a dose-dependent manner. Of note, the in vitro TNF-α inhibition potential of 5b and 5d is comparable to that of curcumin (a naturally occurring diarylheptanoid). Most importantly, oral administration of 4i, 5b, 5d, and 5g (each at 100 mg/kg) but not curcumin (at 100 mg/kg) significantly inhibits LPS-induced TNF-α production in BALB/c mice. Collectively, our findings indicate that these compounds may have potential therapeutic implications for TNF-α-mediated auto-immune/inflammatory disorders.
- Dhuru, Sameer,Bhedi, Dilip,Gophane, Dnyaneshwar,Hirbhagat, Kiran,Nadar, Vijaya,More, Dattatray,Parikh, Sapna,Dalal, Roda,Fonseca, Lyle C.,Kharas, Firuza,Vadnal, Prashant Y.,Vishwakarma, Ram A.,Sivaramakrishnan
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supporting information; experimental part
p. 3784 - 3787
(2011/07/31)
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- Sequential aldol Condensation-Transition metal-Catalyzed addition reactions of aldehydes, methyl ketones, and arylboronic acids
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Sequential aldol condensation of aldehydes with methyl ketones followed by transition metal-catalyzed addition reactions of arylboronic acids to form β-substituted ketones is described. By using the 1,1′;-spirobiindane- 7,7′;-diol (SPINOL)-based phosphite, an asymmetric version of this type of sequential reaction, with up to 92% ee, was also realized. Our study provided an efficient method to access β-substituted ketones and might lead to the development of other sequential/tandem reactions with transition metal-catalyzed addition reactions as the key step.
- Liao, Yuan-Xi,Xing, Chun-Hui,Israel, Matthew,Hu, Qiao-Sheng
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supporting information; experimental part
p. 2058 - 2061
(2011/06/19)
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- A simple and efficient synthesis of pyrazoles in water
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A simple, highly efficient, and environmentally friendly method for the synthesis of substituted 1H-pyrazoles by one-pot condensation reaction of α,β-unsaturated carbonyl compounds with tosyl hydrazide in water was developed. The reaction system exhibited tolerance with various functional groups, Aromatic moiety with both electron-rich and electron-deficient substituents could give desired products in good to excellent yields.
- Wen, Jun,Fu, Yun,Zhang, Ruo-Yi,Zhang, Ji,Chen, Shan-Yong,Yu, Xiao-Qi
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supporting information; experimental part
p. 9618 - 9621
(2011/12/14)
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- Novel and efficient one pot condensation reactions between ketones and aromatic alcohols in the presence of CrO3 producing α,β-unsaturated carbonyl compounds
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We report a new, effective and simple method for preparing α,β-unsaturated carbonyl compounds by reacting ketones and aromatic alcohols at 56 °C in the presence of CrO3 (CrO3 acts as an oxidant and also a catalyst) for around 10 h. The condensation reactions occurred effectively among a wide combination of ketones and alcohols. The procedure is simple and the yields can be high up to 98%. And a probable mechanism is proposed.
- Li, Yanan,Chen, Daoyong
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experimental part
p. 2086 - 2090
(2012/04/04)
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- An Environment-friendly and efficient method for aldol condensation catalyzed by L-Lysine in pure water
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This is a new example of a nonmetallic small-molecule catalyst for direct intermolecular aldol reactions. We found L-lysine is an effective catalyst for this condensation between unmodified acetone and a variety of aldehydes in the presence of pure water. This green catalyst system could be reused.
- Zhang, Yan,Wang, Man Gang,Liang, Jun,Shang, Zhi Cai
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scheme or table
p. 27 - 31
(2010/08/07)
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- Protection-, salt-, and metal-free syntheses of [n]-shogaols by use of dimethylammonium dimethyl carbamate (DIMCARB) without protecting groups
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Shogaols, the pungent principle of ginger, exhibit interesting bioactivities. Practical preparation of shogaols is highly desired. Here we report the protection/deprotection-, salt-, and metalfree synthesis of shogaol in three steps by use of dimethylammonium dimethyl carbamate (DIMCARB), in which DIMCARB smoothly promoted Mannich-type condensation of the ketone donor with the aldehyde acceptor through the iminium cation intermediate. Georg Thieme Verlag Stuttgart.
- Mase, Nobuyuki,Kitagawa, Norihiko,Takabe, Kunihiko
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experimental part
p. 93 - 96
(2010/07/16)
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- One-pot synthesis of optically active allyl esters via lipase-vanadium combo catalysis
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The combination of vanadium-oxo compounds (3 or 4) with a lipase produced the regio- and enantioconvergent transformation of racemic allyl alcohols (1 or 2) into optically active allyl esters. In this system, the vanadium compounds catalyzed the continuous racemization of the alcohols along with the transposition of the hydroxyl group, while the lipase effected the chemo- and enantioselective esterification to achieve the dynamic kinetic resolution.
- Akai, Shuji,Hanada, Ryosuke,Fujiwara, Noboru,Kita, Yasuyuki,Egi, Masahiro
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supporting information; experimental part
p. 4900 - 4903
(2011/01/12)
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- [Hydroxy(tosyloxy)iodo]benzene: A tosyloxylating agent with selectivity for ketones in the reactions with benzalacetones
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The treatment of enolizable ketones containing a conjugated double bond, namely benzalacetones with [hydroxy(tosyloxy)iodo]benzene, leads to regioselective tosyloxylation, thereby giving new compounds (α- tosyloxybenzalacetones).
- Prakash, Om,Sharma, Nitya,Ranjan, Pooja
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experimental part
p. 2875 - 2879
(2010/11/04)
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