- Oxidation of indole with CPO and GOx immobilized on mesoporous molecular sieves
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Green chemistry and environmentally benign reaction engineering play an important role for future industrial processes. It is expected that the number of chemical reactions carried out via enzymatic catalysis will increase strongly. To achieve this aim, stable (viz. leaching and deactivation is prevented) heterogeneous biocatalysts are required. In this study, cross-linked enzyme aggregates of chloroperoxidase were grown in large-pore mesocellular foams (MCF). By changing the various synthesis parameters, the specific activity and the effective activity (viz. the enzyme activity units per mmol of adsorbed enzyme) are improved. The resulting biocatalysts composed of cross-linked chloroperoxidase and cross-linked glucose oxidase were tested in the oxidation of indole. The catalytic test under continuous operation conditions in a fixed-bed reactor confirmed that the cross-linked enzymes are less prone to leaching compared to the physically adsorbed enzymes in the pores of MCF or SBA-15.
- Jung, Dirk,Hartmann, Martin
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- Synthesis, Docking, and Bioavailability of 2′-Oxo-3-phenylspiro[cyclopropane-1,3′-indoline]-2,2-dicarbonitriles as Antibacterial Agents In Silico
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An efficient method has been developed for the synthesis of N-alkylated 2′-oxo-3-phenylspiro[cyclopropane-1,3′-indoline]-2,2-dicarbonitrile from 3-chloroindolin-2-one and 2-benzylidenemalononitrile by using triethylamine as a base at room temperature and obtained the products in moderate to good yields. In extension, the scope of the reaction has been investigated by stepwise and one-pot methods. Furthermore, in silico antibacterial activity was carried out in order to understand possible binding modes of novel derivatives with the active site of DNA gyrase A enzyme, and the results were well complemented. Additionally, absorption, distribution, metabolism, and excretion properties of compounds have shown drug likeness with good oral absorption and moderate blood–brain barrier permeability.
- Avula, Vijay Kumar Reddy,Chintha, Venkata Ramaiah,Vallela, Swetha,Anireddy, Jaya Shree,Chamarthi, Naga Raju,Wudayagiri, Rajendra
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- Kinetics and mechanism of meso-tetraphenylporphyriniron(III) chloride catalyzed oxidation of indole by peroxomonosulphate
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Mechanistic study on meso-tetraphenylporphyriniron(III) chloride (TPP) catalyzed oxidation of indole by peroxomonosulphate in aqueous acetonitrile medium have been carried out. The reaction follows a fractional order (0.57) with respect to substrate and first order with respect to oxidant. The order with respect to catalyst was found to be one. Increase in percentage of acetonitrile decreased the rate of the reaction. The added H+ did not affect the reaction rate. The reaction fails to initiate polymerization and free radical mechanism is ruled out. Activation and thermodynamic parameters have been computed. Nucleophilic attack of the ethylenic bond on the persulphate oxygen in presence of mesotetraphenylporphyriniron( III) chloride is envisaged to explain the reactivity. A suitable kinetic scheme based on the observations was proposed. Significant catalytic activity is observed for the reaction system in the presence of meso-tetraphenylporphyriniron(III) chloride.
- Kungumathilagam,Karunakaran
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- Paramagnetic nuclear magnetic resonance relaxation and molecular mechanics studies of the chloroperoxidase-indole complex: Insights into the mechanism of chloroperoxidase-catalyzed regioselective oxidation of indole
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To unravel the mechanism of chloroperoxidase (CPO)-catalyzed regioselective oxidation of indole, we studied the structure of the CPO-indole complex using nuclear magnetic resonance (NMR) relaxation measurements and computational techniques. The dissociation constant (KD) of the CPO-indole complex was calculated to be approximately 21 mM. The distances (r) between protons of indole and the heme iron calculated via NMR relaxation measurements and molecular docking revealed that the pyrrole ring of indole is oriented toward the heme with its 2-H pointing directly at the heme iron. Both KD and r values are independent of pH in the range of 3.0-6.5. The stability and structure of the CPO-indole complex are also independent of the concentration of chloride or iodide ion. Molecular docking suggests the formation of a hydrogen bond between the NH group of indole and the carboxyl O of Glu 183 in the binding of indole to CPO. Simulated annealing of the CPO-indole complex using r values from NMR experiments as distance restraints reveals that the van der Waals interactions were much stronger than the Coulomb interactions in the binding of indole to CPO, indicating that the association of indole with CPO is primarily governed by hydrophobic rather than electrostatic interactions. This work provides the first experimental and theoretical evidence of the long-sought mechanism that leads to the "unexpected" regioselectivity of the CPO-catalyzed oxidation of indole. The structure of the CPO-indole complex will serve as a lighthouse in guiding the design of CPO mutants with tailor-made activities for biotechnological applications.
- Zhang, Rui,He, Qinghao,Chatfield, David,Wang, Xiaotang
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- Kinetics and mechanism of oxidation of indole by HSO5 -
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Mechanistic studies on the oxidation of indole [IND] by HSO 5- in aqueous CH3CN medium (80:20 v/v) have been carried out, and the reaction is characterized by the rate law -d[HSO 5-]/dt = k[IND][HSO5-]HSO5 - and SO52- are probably the respective electrophiles in acidic and basic mediums. Nucleophilic attack of the ethylenic bond on the persulfate oxygen is envisaged to explain the reactivity. The reaction fails to initiate polymerization, and a radical mechanism is ruled out. Thermodynamic parameters very much suggest a bimolecular process. No significant catalytic activity is observed for the reaction system in the presence of Ag+, Cu2+, and heteroaromatic N-bases.
- Meenakshisundaram, Subbiah,Sarathi
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- Transition-metal-catalyzed electrophilic activation of 1,1-difluoro-1- alkenes: Oxindole synthesis via intramolecular amination
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In the presence of a catalytic amount of palladium(II) chloride, β,β-difluorostyrenes bearing a sulfonamido group at the ortho position were treated with trimethylsilyl trifluoro-methanesulfonate to afford oxindoles in high yield. The reactions proceeded via 5-endo-trig cyclization, hydrolysis, and desulfonylation. This sequence allowed the transformation of difluorostyrenes into free oxindoles in a one-pot operation.
- Tanabe, Hiroyuki,Ichikawa, Junji
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- Inversion kinetics of someE/Z3-(benzylidene)-2-oxo-indoline derivatives and theirin silicoCDK2 docking studies
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The structure-based design of some CDK2 inhibitors with a 3-(benzylidene)indolin-2-one scaffold as potential anticancer agents was realized. Target compounds were obtained asE/Zmixtures and were resolved to correspondingE- andZ-diastereomers.In silicostudies using MOE 2019.01 software revealed better docking on the targeted enzyme for theZ-diastereomer compared to theE-one. A time-dependent kinetic isomerization study was carried out for the inversion ofE/Zdiastereomers in DMSO-d6at room temperature, and were found to obey the first order kinetic reactions. Furthermore, a determination of the kinetic inter-conversion rate order by graphical analysis method and calculation of the rate constant and half-life of this kinetic process were carried out. For the prediction of the stability of the diastereomer(s), a good multiple regression equation was generated between the reaction rates of isomerization and some QM parameters with significantpvalue.
- Mansour, Hany S.,Abd El-Wahab, Hend A. A.,Ali, Ahmed M.,Aboul-Fadl, Tarek
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p. 7839 - 7850
(2021/03/03)
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- Design, synthesis, and in vitro and in vivo anti-angiogenesis study of a novel vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor based on 1,2,3-triazole scaffold
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In the past five years, our team had been committed to click chemistry research, exploring the biological activity of 1,2,3-triazole by synthesizing different target inhibitors. In this study, a series of novel indole-2-one derivatives based on 1,2,3-triazole scaffolds were synthesized for the first time, and their inhibitory activity on vascular endothelial growth factor receptor-2 (VEGFR-2) was tested. Most of the compounds had shown promising activity in the VEGFR-2 kinase assay and had low toxicity to human umbilical vein endothelial cells (HUVECs). The compound 13d (IC50 = 26.38 nM) had better kinase activity inhibition ability than sunitinib (IC50 = 83.20 nM) and was less toxic to HUVECs. Moreover, it had an excellent inhibitory effect on HT-29 and MKN-45 cells. On the one hand, by tube formation assay, transwell, and Western blot analysis, compound 13d could inhibit VEGFR-2 protein phosphorylate on HUVECs, thereby inhibiting HUVECs migration and tube formation. In vivo study, the zebrafish model with VEGFR-2 labeling also verified that compound 13d had more anti-angiogenesis ability than sunitinib. On the other hand, molecular docking and molecular dynamics (MD) simulation results showed that compound 13d could stably bind to the active site of VEGFR-2. Based on the above findings, compound 13d could be considered an effective anti-angiogenesis drug and has more development value than sunitinib.
- Wang, De-pu,Liu, Kai-li,Li, Xin-yang,Lu, Guo-qing,Xue, Wen-han,Qian, Xin-hua,Mohamed O, Kamara,Meng, Fan-hao
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- A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids
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A novel method for the synthesis of 3-monohalooxindoles by acidolysis of isatin-derived 3-phosphate-substituted oxindoles with haloid acids was developed. This synthetic strategy involved the preparation of 3-phosphate-substituted oxindole intermediates and SN1 reactions with haloid acids. This new procedure features mild reaction conditions, simple operation, good yield, readily available and inexpensive starting materials, and gram-scalability.
- Huang, Tiao,Kong, Dulin,Li, Yue,Liu, Li,Wu, Mingshu
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p. 2321 - 2328
(2021/09/22)
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- Fenton chemistry enables the catalytic oxidative rearrangement of indoles using hydrogen peroxide
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Oxidative rearrangement of indoles is an important transformation to yield 2-oxindoles and spirooxindoles, which are present in many pharmaceutical agents and bioactive natural products. Previous oxidation methods show either broad applicability or greenness but rarely achieve both. Reported is the discovery of Fenton chemistry-enabled green catalytic oxidative rearrangement of indoles, which has wide substrate scope (42 examples) and greenness (water as the only stoichiometric byproduct) at the same time. Detailed mechanistic studies revealed that the Fenton chemistry generated hydroxyl radicals that further oxidize bromide to reactive brominating species (RBS: bromine or hypobromous acid). Thisin situgenerated RBS is the real catalyst for the oxidative rearrangement. Importantly, the RBS is generated under neutral conditions, which addresses a long-lasting problem of many haloperoxidase mimics that require a strong acid for the oxidation of bromide with hydrogen peroxide. It is expected that this new catalytic Fenton-halide system will find wide applications in organic synthesis.
- Zhao, Guodong,Liang, Lixin,Wang, Eryu,Lou, Shaoyan,Qi, Rui,Tong, Rongbiao
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supporting information
p. 2300 - 2307
(2021/04/12)
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- Green method for preparing oxindole derivative
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The invention relates to the technical field of green organic synthesis, and provides a green method for preparing oxindole derivatives, which comprises the following steps: taking indole compounds with different functional groups as raw materials, under the conditions of room temperature, opening and neutral, adopting MBrx (M is Fe,Fe,Ce and the like) as a catalyst with X equal to 2 or 3, and adopting hydrogen peroxide as a sole oxidant to generate active bromine (RBS) in situ, and catalytically synthesizing the oxindole derivative. According to the method disclosed by the invention, MBrx (such as FeBr2, CeBr3 and the like) is used as the catalyst, so that an expensive or complex catalyst is avoided, and the method is green, environment-friendly, safe, simple, efficient, mild in reaction condition and wide in substrate application range, has a relatively good application prospect and is expected to be widely applied to organic synthesis, fine chemical engineering and pharmaceutical industry.
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Paragraph 0027-0029
(2021/06/26)
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- Oxidative Cleavage of Indoles Mediated by Urea Hydrogen Peroxide or H2O2 in Polar Solvents
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The oxidative cleavage of indoles (Witkop oxidation) involving the use of H2O2 or urea hydrogen peroxide in combination with a polar solvent has been described. Among these solvents, 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) stands out as the one affording the corresponding 2-ketoacetanilides generally in higher yields The protocol described has also enabled the oxidation of different pyrroles and furans derivatives. Furthermore, the procedure was implemented in a larger-scale and HFIP was distilled from the reaction mixture and reused (up to 4 cycles) without a significant detriment in the reaction outcome, which remarks its sustainability and applicability. (Figure presented.).
- Llopis, Natalia,Gisbert, Patricia,Baeza, Alejandro
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supporting information
p. 3245 - 3249
(2021/06/08)
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- Dihalide impurity in ziprasidone hydrochloride intermediate and preparation method of dihalide impurity
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The invention provides a dihalide impurity in a ziprasidone hydrochloride intermediate. The dihalide impurity has a structure shown as a formula 1. On the basis that the ziprasidone hydrochloride intermediate can bring in the dechlorination impurity or the preparation process contains the dechlorination step, the dechlorination impurity with a specific structure is obtained, and the preparation steps of the corresponding impurity are provided, so a corresponding technical support is provided for preparation of ziprasidone hydrochloride. The synthesis method provided by the invention has the advantages of simple process, strong controllability and mild conditions, can be used for quality standard establishment and quality control links of ziprasidone hydrochloride process research and development, production and the like, and provides technical support for ziprasidone hydrochloride medication safety. The method can be used for quality research such as qualitative and quantitative analysis of impurities in ziprasidone hydrochloride synthesis, so that the quality of ziprasidone hydrochloride can be improved, and important guiding significance is provided for reducing the medication risk of ziprasidone hydrochloride.
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- Iodine-Catalyzed Aerobic Oxidation of Spirovinylcyclopropyl Oxindoles to Form Spiro-1,2-dioxolanes Diastereoselectively
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A novel method of iodine-catalyzed aerobic oxidation with spirovinylcyclopropyl oxindoles under mild conditions has been described. A series of spiro-1,2-dioxolanes were prepared in good to excellent yields and considerable diastereoselectivities. The new approach is operationally simple, scalable, and tolerant of various functional groups.
- Xiong, Cheng,Cheng, Kunpeng,Wang, Jiahua,Yang, Fulai,Lu, Jinrong,Zhou, Qingfa
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p. 9386 - 9395
(2020/08/14)
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- Pharmacophore modeling and 3D-QSAR study of indole and isatin derivatives as antiamyloidogenic agents targeting Alzheimer’s disease
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Thirty-six novel indole-containing compounds, mainly 3-(2-phenylhydrazono) isatins and structurally related 1H-indole-3-carbaldehyde derivatives, were synthesized and assayed as inhibitors of beta amyloid (Aβ) aggregation, a hallmark of pathophysiology of Alzheimer’s disease. The newly synthesized molecules spanned their IC50 values from sub- to two-digit micromolar range, bearing further information into structure-activity relationships. Some of the new compounds showed interesting multitarget activity, by inhibiting monoamine oxidases A and B. A cell-based assay in tau overexpressing bacterial cells disclosed a promising additional activity of some derivatives against tau aggregation. The accumulated data of either about ninety published and thirty-six newly synthesized molecules were used to generate a pharmacophore hypothesis of antiamyloidogenic activity exerted in a wide range of potencies, satisfactorily discriminating the ‘active’ compounds from the ‘inactive’ (poorly active) ones. An atom-based 3D-QSAR model was also derived for about 80% of ‘active’ compounds, i.e., those achieving finite IC50 values lower than 100 μM. The 3D-QSAR model (encompassing 4 PLS factors), featuring acceptable predictive statistics either in the training set (n = 45, q2 = 0.596) and in the external test set (n = 14, r2ext = 0.695), usefully complemented the pharmacophore model by identifying the physicochemical features mainly correlated with the Aβ anti-aggregating potency of the indole and isatin derivatives studied herein.
- Purgatorio, Rosa,Gambacorta, Nicola,Catto, Marco,de Candia, Modesto,Pisani, Leonardo,Espargaró, Alba,Sabaté, Raimon,Cellamare, Saverio,Nicolotti, Orazio,Altomare, Cosimo D.
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- Gold(I)-Thiolate Oligomers for Catalytic Hydrogenation of Nitroaromatics in Aqueous and Organic Medium
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Thiolated gold nanoclusters (AuNCs) have been introduced to efficiently and selectively catalyze the hydrogenation of nitroaromatics due to the strong interaction of their S?Au-S staple motifs with the nitro groups of nitroaromatics. However, without a gold core, gold(I)-thiolate oligomers (AuSOs) with S?Au-S staple motifs are rarely explored as catalysts for nitroaromatics. Here, we report a straightforward strategy for the synthesis of AuSOs through hydroxyl radical-induced leaching of glutathione-capped gold nanoparticles (GSH-AuNPs). Raman spectroscopy and matrix-assisted laser desorption/ionization-time of flight mass spectrometry demonstrated that hydroxyl radical-triggered etching of the GSH-AuNPs resulted in the production of AuSOs, including Au4(GSH)7 and Au7(GSH)9. The AuSOs were found to catalyze NaBH4-mediated hydrogenation of 4-nitrophenol to 4-aminophenol with a chemoselectivity of ～100 percent and a normalized rate constant (Knor) of 4.8×105 s? g?1. In addition to the high affinity of the S?Au?S staple motifs for 4-nitrophenol, the unusual catalytic activity of the AuSOs was attributable to the fact that they efficiently catalyzed the production of H2 from NaBH4 and the reaction of dissolved oxygen and NaBH4. The chemoselectivity and applicability of the AuSOs were further verified by performing the catalytic reaction of methyl 2-(2-nitrophenyl) acetate or methyl 4-nitrobenzoate with NaBH4.
- You, Jyun-Guo,Jin, Dun-Yuan,Tseng, Wei-Bin,Tseng, Wei-Lung,Lin, Po-Chiao
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p. 4558 - 4567
(2020/08/19)
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- PIII/PV=O Catalyzed Cascade Synthesis of N-Functionalized Azaheterocycles
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An organocatalytic method for the modular synthesis of diverse N-aryl and N-alkyl azaheterocycles (indoles, oxindoles, benzimidazoles, and quinoxalinediones) is reported. The method employs a small-ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide) and a hydrosilane reductant to drive the conversion of ortho-functionalized nitroarenes into azaheterocycles through sequential intermolecular reductive C?N cross coupling with boronic acids, followed by intramolecular cyclization. This method enables the rapid construction of azaheterocycles from readily available building blocks, including a regiospecific approach to N-substituted benzimidazoles and quinoxalinediones.
- Li, Gen,Luzung, Michael R.,Nykaza, Trevor V.,Radosevich, Alexander T.,Yang, Junyu
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supporting information
p. 4505 - 4510
(2020/02/05)
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- Synthesis and biological evaluation of 3-substituted 2-oxindole derivatives as new glycogen synthase kinase 3β inhibitors
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Glycogen synthase kinase 3β (GSK-3β) is a widely investigated molecular target for numerous diseases including Alzheimer's disease, cancer, and diabetes mellitus. Inhibition of GSK-3β activity has become an attractive approach for treatment of diabetes and cancer. We report the discovery of novel GSK-3β inhibitors of 3-arylidene-2-oxindole scaffold with promising activity. The most potent compound 3a inhibits GSK-3β with IC50 4.19 nM. In a cell-based assay 3a shows no significant leucocyte toxicity at 10 μM and is moderately cytotoxic against A549 cells. Compound 3a demonstrated high antidiabetic efficacy in obese streptozotocin-treated rats improving glucose tolerance at a dose of 50 mg/kg body weight thus representing an interesting lead for further optimization.
- Lozinskaya, Natalia A.,Babkov, Denis A.,Zaryanova, Ekaterina V.,Bezsonova, Elena N.,Efremov, Alexander M.,Tsymlyakov, Michael D.,Anikina, Lada V.,Zakharyascheva, Olga Yu.,Borisov, Alexander V.,Perfilova, Valentina N.,Tyurenkov, Ivan N.,Proskurnina, Marina V.,Spasov, Alexander A.
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p. 1804 - 1817
(2019/03/23)
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- Enantioselective Arylation of 3-Carboxamide Oxindoles with Quinone Monoimines and Synthesis of Chiral Spirooxindole-benzofuranones
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A highly enantioselective arylation of 3-carboxamide oxoindoles with quinone monoimines is described. Various 3-aryl-3-carboxamide oxindoles with an all-carbon quaternary center were obtained in moderate to good yields (up to 99%) with moderate to good enantioselectivities (up to 98%) in the presence of a bifunctional thiourea-tertiary amine catalyst. The absolute configuration of one product was determined by an X-ray crystal structural analysis and the absolute configurations of the other products can be assigned by analogy. Moreover, several chiral spirooxindole-benzofuranones were synthesized from the 3-aryl-3-carboxamide oxindoles in moderate yields with moderate to good enantioselectivities.
- Chen, Hui,Liu, Hui,Zhao, Si-Han,Cheng, Shao-Bing,Xu, Xiao-Ying,Yuan, Wei-Cheng,Zhang, Xiao-Mei
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supporting information
p. 1067 - 1072
(2019/05/24)
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- Regioselective oxidation of indoles to 2-oxindoles
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Facile regioselective oxidation of indoles to 2-oxindoles promoted by sulfuric acid adsorbed on silica gel is reported. The demonstrated practical site-selective heterogeneous oxidation reactions conveniently take place with a broad substrate scope and functional group tolerances. The present oxidation strategy is also employed to accomplish the total synthesis of natural products donaxaridine and donaxarine. On the basis of analytical and spectral data it is evidenced that donaxarine stays in equilibrium with its hydrated ring opened form. The structural features essential for this type of oxidation and plausible mechanism are discussed in brief.
- Shelar, Santosh V.,Argade, Narshinha P.
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p. 6671 - 6677
(2019/07/16)
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- Method for synthesizing 2,5-dibromo phenylacetic acid
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The invention discloses a method for synthesizing 2,5-dibromo phenylacetic acid. The method comprises the following step: by taking isatin as a raw material, carrying out carbonyl reduction, 5-site bromo reactions and diazotization hydrolysis reactions, thereby obtaining 2,5-dibromo phenylacetic acid, wherein the step of carbonyl reduction is carried out through catalytic hydrogenation reduction;the step of 5-site bromo reactions is carried out with NBS (Bromo-Succinimide) as a bromo agent; and the step of diazotization is carried out with a sodium nitrite/hydrobromic acid system. HBr/cuprousbromide is adopted as a hydrolysis bromo agent. The method has the advantages of being wide in raw material source, mild in reaction condition, high in yield, excellent in quality, low in finished product cost, and the like.
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Paragraph 0019
(2018/12/02)
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- Novel RIP1 kinase inhibitor containing pyrrole ring and indoline structure and application thereof
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The invention relates to a novel RIP1 kinase inhibitor containing a pyrrole ring and an indoline structure and application in preparing drugs for treating inflammation, ischemic diseases and cell injury type diseases.
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Paragraph 0030-0031
(2018/07/30)
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- Design and Synthesis of DNA-Interactive β-Carboline–Oxindole Hybrids as Cytotoxic and Apoptosis-Inducing Agents
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A new series of (E)-3-[(1-aryl-9H-pyrido[3,4-b]indol-3-yl)methylene]indolin-2-one hybrids were synthesized and evaluated for their in vitro cytotoxic activity against a panel of selected human cancer cell lines, namely, HCT-15, HCT-116, A549, NCI-H460, and MCF-7, including HFL. Among the tested compounds, (E)-1-benzyl-5-bromo-3-{[1-(2,5-dimethoxyphenyl)-9H-pyrido[3,4-b]indol-3-yl]methylene}indolin-2-one (10 s) showed potent cytotoxicity against HCT-15 cancer cells with an IC50 value of 1.43±0.26 μm and a GI50 value of 0.89±0.06 μm. Notably, induction of apoptosis by 10 s on the HCT-15 cell line was characterized by using different staining techniques, such as acridine orange/ethidium bromide (AO/EB) and DAPI. Further, to understand the mechanism of anticancer effects, various assays such as annexin V-FITC/PI, DCFDA, and JC-1were performed. The flow cytometric analysis revealed that compound 10 s arrests the HCT-15 cancer cells at the G0/G1 phase of the cell cycle. Additionally, western blot analysis indicated that treatment of 10 s on HCT-15 cancer cells led to decreased expression of anti-apoptotic Bcl-2 and increased protein expression of both pro-apoptotic Bax and caspase-3, -8, and -9, and cleaved PARP with reference to actin. Next, a clonogenic assay revealed the inhibition of colony formation in HCT-15 cancer cells by 10 s in a dose-dependent manner. Moreover, upon testing on normal human lung cells (HFL), the compounds were observed to be safer with a low toxicity profile. In addition, viscosity and molecular-docking studies showed that compound 10 s has typical intercalation with DNA.
- Tokala, Ramya,Thatikonda, Sowjanya,Vanteddu, Usha Sree,Sana, Sravani,Godugu, Chandraiah,Shankaraiah, Nagula
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p. 1909 - 1922
(2018/09/14)
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- Cinchona-alkaloid-catalyzed enantioselective hydroxymethylation of 3-fluorooxindoles with paraformaldehyde
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Cinchona-alkaloid-catalyzed hydroxymethylation of 3-fluorooxindoles using paraformaldehyde as the C1 unit was achieved. A wide range of 3-fluorooxindoles was successfully reacted to give the corresponding 3-fluoro-3-hydroxymethyloxindoles with high efficiency and moderate to good enantioselectivity.
- Zhao, Jian-bo,Ren, Xinfeng,Zheng, Bu-quan,Ji, Jian,Qiu, Zi-bin,Li, Ya
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supporting information
p. 44 - 51
(2018/10/02)
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- Chalcone scaffolds as photofunctional hybrid material of indolin-2-one-functionalized siloxy framework for optical sensing of Cu2+
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Owing to their easy approachability and high degree of structural and functional diversity, many multicomponent reactions such as 1,3-dipolar cycloaddition have been a rich source of conjugated π-systems, functionalised chromophores and active molecules. Despite their high potential for investigation and practical benefits, few products have thus far been scrutinized for their metal sensing abilities. In the present study, indolin-2-one chalcones bearing siloxy molecular systems were synthesized by a [2+3] cycloaddition-based reaction sequence. A designed chemosensor exhibited an optical (absorption spectra) response toward Cu2+ ions in an acetonitrile solution. Different aspects of the sensing phenomena such as selectivity and association constants were studied in detail using UV-vis spectroscopy. The calibration plot was linear (R2 = 0.9966) over a large range of Cu2+ ion concentrations (10 μM). This novel effort has initiated a well-organized method for the efficient improvement of cation sensors with triazole for detecting heavy metal pollutants in environmental and healthcare fields on a large scale.
- Singh, Gurjaspreet,Kalra, Pooja,Arora, Aanchal,Singh, Akshpreet,Sharma, Geetika,Sanchita,Satija, Pinky
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p. 16902 - 16910
(2018/10/24)
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- Synthesis of 2-Oxindoles from Substituted Indoles by Hypervalent-Iodine Oxidation
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A practical conversion of indoles into the corresponding 2-oxindoles is achieved efficiently using a hypervalent iodine reagent. This oxidation is amenable to different substituted indoles, and allows the synthesis of a wide range of synthetically valuable substituted 2-oxindoles in up to 90 % yield. Furthermore, Ropinirole, a drug used to alleviate the symptoms of Parkinson's disease, was synthesized in three steps in an overall yield of 44 % using this method.
- Jiang, Xinpeng,Zheng, Cong,Lei, Lijun,Lin, Kai,Yu, Chuanming
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p. 1437 - 1442
(2018/04/06)
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- Method for synthesizing indole-2-ketone compound
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The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a method for synthesizing an indole-2-ketone compound. Indole-2-ketone compound synthesis is difficultly industrialized due to the problems of poor yield, cost and environmental protection in the prior art, the method includes the steps: taking a compound X as a catalyst in a hydrous organic solvent; performing reaction on indole and water under the condition of oxidizing agents to obtain the indole-2-ketone compound. The compound X is preferably iodine, and the indole-2-ketone compound is applicable to the field of organic synthesis and medicine.
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Paragraph 0051; 0053
(2018/11/03)
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- Synthesis of substituted t-butyl 3-alkyloxindole-3-carboxylates from di-t-butyl (2-nitrophenyl)malonates
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Using a novel tandem reduction-cyclization, we synthesized t-butyl 3-alkyloxindole-3-carboxylates from the di-t-butyl 2-alkyl-2-(2-nitrophenyl)malonate. Introduction of an α-substituent to the di-t-butyl 2-(2-nitrophenyl)-malonates and addition of acid promoted reactivity. This methodology was successfully applied to gram-scale-synthesis of the t-butyl 3-methyloxindole-3-carboxylate 1 and 3-hydroxymethyl-3-methyloxindole 2 without silica gel column chromatography.
- Yamai, Yu-Suke,Tanaka, Akio,Yajima, Tatsuo,Ishida, Kyoji,Natsutani, Itaru,Uesato, Shinichi,Nagaoka, Yasuo,Sumiyoshi, Takaaki
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p. 192 - 210
(2019/04/27)
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- Total synthesis and biological evaluation of spirotryprostatin A analogs
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Based on the spirotryprostatin A structure, a series of compounds belonging to spiro-indolyl diketopiperazine structural class were designed and synthesized, which embody an oxindole with an all-carbon quaternary stereocenter. The total synthesis can efficiently be accessed in a seven-step reaction sequence with 18–28% overall yield from commercially available materials, and a highly enantioselective 1,3-dipolar cycloaddition, N-acylation of the resulting stereochemically complex spiro[pyrrolidin-3,3′-oxindole]s core with Fmoc-L-pro-Cl and spontaneous ring closure upon N-deprotection were obtained. The synthesized compounds 13a–e and 15a–e were evaluated for their antibacterial activities. The result showed that compounds 13b and 15b were active only against Gram-positive bacteria, and selective antibacterial activity was exhibited by compounds 13d and 13e against Streptococcus lactis. Further, all the remaining compounds showed a certain degree of antibacterial activity. In addition, the structure–activity relationship is also discussed.
- Ma, Yangmin,Fan, Chao,Jia, Bin,Cheng, Pei,Liu, Jia,Ma, Yuqiang,Qiao, Ke
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p. 737 - 746
(2017/10/17)
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- Synthesis of novel 3-(benzothiazol-2-ylmethylene)indolin-2-ones
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A mild method for the synthesis of 3-(benzothiazol-2-ylmethylene)indolin-2-ones via the aldol condensation of substituted indolin-2-ones and benzothiazole-2-carbaldehyde is described. This new procedure has significant advantages, such as mild conditions, high yields and simple work-up.
- Zhang, Chao,Xu, Juan,Zhao, Xinyu,Kang, Congmin
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p. 537 - 540
(2017/10/03)
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- Discovery of novel polycyclic spiro-fused carbocyclicoxindole-based anticancer agents
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A series of novel polycyclic spiro-fused carbocyclicoxindoles were synthesized and investigated for their in?vitro antiproliferative activities against nine human cancer cell lines. Five compounds (10i, 10l, 10n, 10p, and 10r) demonstrated anticancer activities against A2780s cells with IC50values of less than 30?μM. In particular, compound 10i showed anticancer activities against seven cancer cell lines and stronger activities than cisplatin in A2780s, A2780T, CT26, and HCT116?cells. Further studies illustrated that compound 10i arrested cell cycle in G1 phase and induced apoptosis of HCT116?cells. This compound also effectively increased the protein levels of cleaved caspase-3, p53, and MDM2. Molecular docking results revealed that compound 10i could bind well to the p53-binding site on MDM2, indicating that it might work by blocking the MDM2-p53 interactions.
- Zhang, Lidan,Ren, Wen,Wang, Xiaoyan,Zhang, Jiaying,Liu, Jie,Zhao, Lifeng,Zhang, Xia
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p. 1071 - 1082
(2016/12/28)
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- Aromatic substitution spiro indolyl diketopiperazine compound and synthesis method thereof
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The invention discloses an aromatic substitution spiro indolyl diketopiperazine compound and a synthesis method thereof. Glycine is used as a raw material and subjected to esterification reaction with methyl alcohol and thionyl chloride to obtain methyl glycinate hydrochloride, methyl glycinate hydrochloride and aromatic aldehyde are subjected to condensation reaction to obtain Schiff base, isatin is used as a raw material and subjected to reduction reaction under the action of hydrazine hydrate to obtain indoline-2-ketone, indoline-2-ketone and benzaldehyde are subjected to Knoevenagel reaction under piperidine catalysis to obtain 3-phenylidene-1,3-dihydro-2H-indol-2 ketone, 3-phenylidene-1,3-dihydro-2H-indol-2 ketone and Schiff base are subjected to 1,3-dipole cycloaddition reaction under catalysis of chiral ligand (S)-TF-BiphamPhos/AgoAc to obtain spiro pyrrolidine, and protecting group removal and ring closure are carried out on spiro pyrrolidine and N-(9-fluorene methoxycarbonyl)-L-prolyl chloride through base catalysis to obtain the target product. The method has the advantages of being simple in path, high in yield, high in diastereoselectivity and single in product spatial configuration, and the raw materials are low in price and easy to obtain.
- -
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Paragraph 0040; 0041
(2017/08/28)
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- A safe and selective method for reduction of 2-nitrophenylacetic acid systems to N-aryl hydroxamic acids using continuous flow hydrogenation
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The cyclic hydroxamic acid functional group is critical to the biological activity of numerous natural products and drug candidates. Efficient, reliable, and green synthetic methods to produce cyclic hydroxamic acids are needed. Herein, flow hydrogenation has been explored as a novel approach toward achieving the selective partial reduction of 2-nitrophenylacetic acid to 1-hydroxyindolin-2-one. The bidentate ligand, 1,10-phenanthroline, has been identified as a unique inhibitor for modulating product selectivity in this Pt/C-catalyzed process. Under the newly optimized reaction conditions, the targeted hydroxamic acid is produced with high selectivity (49:1) over the lactam by-product. The scope of the reaction is demonstrated for a variety of 2-nitrophenylacetic acid derivatives.
- Ichire, Ogar,Jans, Petra,Parfenov, Galina,Dounay, Amy B.
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supporting information
p. 582 - 585
(2017/01/16)
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- SUBSTITUTED P-PHENYLENEDIAMINES AS NEW OXIDATION DYE PRECURSOR PRODUCTS OF THE DEVELOPER TYPE
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Compounds, and agents for oxidatively changing the color of keratinic fibers that include such compounds, in particular human hair, in a cosmetic carrier. The compounds are at least one oxidation dye precursor product of formula (I) and/or physiologically acceptable salt thereof, in which R1, R2, R3, R4 independently of one another, stand for a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a hydroxy-(C1-C6)-alkyl group, a polyhydroxy-(C2-C6)-alkyl group, or a C1-C6-alkoxy-C2-C6-alkyl group, n stands for an integer from 2 to 6, and Z stands for an aromatic or aliphatic heterocycle or for an aromatic or aliphatic carbocycle.
- -
-
Paragraph 0218; 0219; 0220; 0221; 0222; 0223
(2017/07/06)
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- Hydrogenation Properties of Nanostructured Tungsten Carbide Catalysts in a Continuous-Flow Reactor
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Tungsten monocarbide (WC) obtained through a urea glass route showed a high activity and chemoselectivity for the continuous-flow reduction of a variety of nitro compounds under milder conditions than those reported previously. The favorable effect of the nanostructure was shown by comparison with other commercially available WC materials. Moreover, WC functioned as an efficient support for Ni nanoparticles. This expanded its range of applicability and led to a bimetallic Ni@WC composite characterized by a high activity for the hydrogenation of cardanol, a phenolic lipid obtained from cashew nut shells.
- Braun, Max,Esposito, Davide
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p. 393 - 397
(2017/02/15)
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- Copper-Catalyzed Coupling Reaction of (Hetero)Aryl Chlorides and Amides
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Cu2O/N,N′-bis(thiophen-2-ylmethyl)oxalamide is established to be an effective catalyst system for Goldberg amidation with inferior reactive (hetero)aryl chlorides, which have not been efficiently documented by Cu-catalysis to date. The reaction is well liberalized toward a variety of functionalized (hetero)aryl chlorides and a wide range of aromatic and aliphatic primary amides in good to excellent yields. Furthermore, the arylation of lactams and oxazolidinones is achieved. The present catalytic system also accomplished an intramolecular cross-coupling product.
- De, Subhadip,Yin, Junli,Ma, Dawei
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p. 4864 - 4867
(2017/09/23)
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- Characterization of 2-Oxindole Forming Heme Enzyme MarE, Expanding the Functional Diversity of the Tryptophan Dioxygenase Superfamily
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3-Substituted 2-oxindoles are important structural motifs found in many biologically active natural products and pharmaceutical lead compounds. Here, we report an enzymatic formation of the 3-substituted 2-oxindoles catalyzed by MarE in the maremycin biosynthetic pathway in Streptomyces sp. B9173. MarE is a homologue of FeII/heme-dependent tryptophan 2,3-dioxygenases (TDOs). Typical TDOs usually catalyze the insertion of two oxygen atoms from O2 into an indole ring to generate N-formylkynurenine (NFK)-like products. In contrast, MarE catalyzes the insertion of a single oxygen atom from O2 into an indole ring, to probably generate an epoxyindole intermediate that undergoes an unprecedented 2,3-hydride migration to form 2-oxindole structure. MarE shows substrate robustness to catalyze the conversion of a series of 3-substituted indoles into their corresponding 3-substituted 2-oxindoles. Although containing most key amino acid residues conserved in well-known TDO homologues, MarE falls into a separate new subgroup in the phylogenetic tree. The characterization of MarE and its homologue enriches the functional diversities of TDO superfamily and provides a new strategy for discovering novel natural products containing 3-substituted 2-oxindole pharmacophores by genome mining.
- Zhang, Yuyang,Zou, Yi,Brock, Nelson L.,Huang, Tingting,Lan, Yingxia,Wang, Xiaozheng,Deng, Zixin,Tang, Yi,Lin, Shuangjun
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supporting information
p. 11887 - 11894
(2017/09/07)
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- Palladium-catalyzed tandem addition/cyclization in aqueous medium: Synthesis of 2-arylindoles
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An efficient protocol to construct 2-arylindoles was developed through palladium-catalyzed tandem addition/cyclization of potassium aryltrifluoroborates with aliphatic nitriles in aqueous medium. The use of water as the reaction medium makes the synthesis process environmentally benign. A plausible mechanism for the formation of 2-arylindoles involving sequential nucleophilic addition followed by an intramolecular cyclization is proposed. Moreover, the utility of this catalytic tandem transformation was also demonstrated in an efficient gram-scale synthesis. This method provides an alternative synthetic tool for accessing a more diverse array of 2-arylindoles.
- Yu, Shuling,Hu, Kun,Gong, Julin,Qi, Linjun,Zhu, Jianghe,Zhang, Yetong,Cheng, Tianxing,Chen, Jiuxi
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p. 4300 - 4307
(2017/07/10)
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- Copper powder-catalyzed chelation-assisted cascade reaction of: O -chloroarylacetic acids with amines under solvent- and ligand-free conditions: Synthesis of oxindoles
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An efficient method to construct oxindole scaffolds from o-chloroarylacetic acids/esters with amines has been explored. This cascade protocol involves the in situ generation of o-aminoarylacetic acid derivatives by the copper powder catalyzed and weak O-chelation assisted Ullmann amination of unactivated C-Cl bonds under air, and solvent-/ligand-free conditions followed by annulative N-acylation.
- Li, Jiang-Sheng,Chen, Guo-Qin,Yang, Qian,Li, Zhi-Wei,Liu, Ci-Zhi,Huang, Peng-Mian
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p. 45227 - 45231
(2017/10/13)
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- Method for preparing indole and derivatives thereof
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The invention discloses a method for preparing indole and derivatives of indole. The method for preparing indole and the derivatives of indole is characterized by comprising the following two steps that (1) a catalyst, a ligand and alkali are added in a reaction tube, under the protection of nitrogen, beta-hydroxy ketone or ester is reacted with a mixed solution of o-nitro aryl halides for 3 to 8h in an oil bath pan at the temperature of 90 to 120 DEG C, and then cooled to room temperature after reaction, and extracted, washed, dried and subjected to chromatography to obtain a product of o-nitro alpha-aryl ketone or ester; (2) o-nitro alpha-aryl ketone or ester obtained in the step (1), a reducing agent system and a solvent are added to the reaction tube, and reacted for 3 to 8h at the temperature of 60 to 100 DEG C, and then extracted, washed, dried and subjected to chromatography after being reacted to obtain a target product of indole and the derivatives of indole. Reaction raw materials, the catalyst, the ligand, the alkali and the solvent used in the invention are all industrial commodities, and simple and readily available, wide in sources, cheap in price, and further very stable in performances, and with no need for special storage conditions; in addition, the method for preparing indole and the derivatives of indole disclosed by the invention has the characteristics of low cost, high yield, simple process, less pollution and the like.
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-
- Iridium-Catalysed Cascade Synthesis of Oxindoles Using Diazo Compounds: A Quick Entry to C-7-Functionalized Oxindoles
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A cascade iridium-catalysed oxindole synthesis was achieved using pyridyl-protected anilines and bis(2,2,2-trifluoroethyl) 2-diazomalonate. The developed protocol is simple and scalable, and has a broad scope and excellent regioselectivity. The pyridyl directing group can easily be removed. The method was further extended to give C-7-functionalized oxindole derivatives in a straightforward manner. The role of bis(2,2,2-trifluoroethyl) 2-diazomalonate for oxindole preparation has been explored.
- Karmakar, Ujjwal,Das, Debapratim,Samanta, Rajarshi
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p. 2780 - 2788
(2017/05/29)
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- Synthesis of Oxindoles and Benzofuranones via Oxidation of 2-Heterocyclic BMIDAs
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The synthesis of functionalized oxindoles and benzofuranones via oxidation of 2-BMIDA indoles and benzofurans, respectively, is described. Interconversion of boron species (BMIDA→BF3K) was necessary to enable oxidation and overcome boronic acid stability issues associated with a difficult BMIDA hydrolysis. Overall, a robust process was developed that allowed access to a small library of oxindole and benzofuranone products and facilitated the step-efficient synthesis of biologically active compounds containing the oxindole pharmaco-phore.
- Seath, Ciaran P.,Fyfe, James W. B.,Molloy, John J.,Watson, Allan J. B.
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p. 891 - 898
(2017/02/15)
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- Synthesis of oxindole from acetanilide via Ir(iii)-catalyzed C-H carbenoid functionalization
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Herein we disclose the first report on the synthesis of oxindole derivatives from acetanilide via Ir(iii)-catalyzed intermolecular C-H functionalization with diazotized Meldrum's acid. A broad range of substituted anilides were found to react smoothly under the Ir(iii)-catalytic system to afford the corresponding N-protected oxindoles. The N-protecting groups, such as Ac, Bz or Piv, can be easily removed to furnish the oxindole. Various synthetic applications of the synthesized oxindole were also demonstrated.
- Patel, Pitambar,Borah, Gongutri
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supporting information
p. 443 - 446
(2017/01/03)
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- A Palladium-Catalyzed Double Carbonylation Approach to Isatins from 2-Iodoanilines
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A high-yielding procedure for the synthesis of isatins has been developed. Sequential Pd-catalyzed double carbonylation of 2-iodoanilines with near stoichiometric amounts of CO followed by acid-promoted cyclization readily affords an array of isatins. The conversion of 2-iodoanilines to isatins in good to excellent yields was found to proceed with good functional group tolerance. This protocol proved adaptable to 13C-isotope labeling of isatins, which was extended to the synthesis of the 13C-isotope labeled antiviral drug metisazone and the experimental anti-schizophrenia drug ML137.
- Laursen, Simon R.,Jensen, Mikkel T.,Lindhardt, Anders T.,Jacobsen, Mikkel F.,Skrydstrup, Troels
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supporting information
p. 1881 - 1885
(2016/05/09)
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- A Benzisoelenazolone modified pyrrole methyl ester substituted indole ketone compound and use thereof
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The invention discloses a benzisoselenazolone-modified pyrrolyl formate-substituted indolone compound and a use thereof. The invention depends on and claims the priority of a Chinese patent application 201110105248.0 submitted on April 26, 2011. Through reference, all contents of the Chinese patent application 201110105248.0 are incorporated into the invention. The benzisoselenazolone-modified pyrrolyl formate-substituted indolone compound is shown in the general formula I. The 2-indolone compound provided by the invention has excellent antitumor activity and can be widely used for preparation of antitumor drugs.
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-
Paragraph 0116-0119
(2016/10/08)
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- Design, synthesis and apoptosis inducing effect of novel (Z)-3-(3′-methoxy-4′-(2-amino-2-oxoethoxy)-benzylidene)indolin-2-ones as potential antitumour agents
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A series of new (Z)-3-(3′-methoxy-4′-(2-amino-2-oxoethoxy)benzylidene)indolin-2-one derivatives has been synthesized and evaluated for their cytotoxic activity against selected human cancer cell lines of prostate (PC-3 and DU-145), breast (BT-549 and MDA-MB-231) and non-tumorigenic prostate epithelial cells (RWPE-1). Among the tested, one of the compounds 4p exhibited potent cytotoxicity selectively on prostate cancer cell lines (PC-3 and DU-145; IC50: 1.89 ± 0.6 and 1.94 ± 0.2 μM, respectively). Further experiments were conducted with 4p on PC-3 cancer cells to study the mechanisms of growth inhibition and apoptosis inducing effect. Treatment of PC-3 cells with test compound 4p resulted in inhibition of cell migration through disorganization of F-actin protein. The flow-cytometry analysis results showed that the compound arrested PC-3 cancer cells in the G2/M phase of cell cycle in a dose dependent manner. Hoechst staining and annexin-V binding assay revealed that the compound 4p inhibited tumor cell proliferation through induction of apoptosis. Western blot studies demonstrated that the compound 4p treatment led to activation of caspase-3, increased expression of pro-apoptotic Bax and significantly decreased expression of anti-apoptotic Bcl-2 in human prostate cancer PC-3 cells. In addition, the mitochondrial membrane potential (ΔΦm) was also affected and the levels of intracellular Ca2+ were raised.
- Senwar, Kishna Ram,Reddy, T. Srinivasa,Thummuri, Dinesh,Sharma, Pankaj,Naidu,Srinivasulu, Gannoju,Shankaraiah, Nagula
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- New (E)-1-alkyl-1H-benzo[d]imidazol-2-yl)methylene)indolin-2-ones: Synthesis, in vitro cytotoxicity evaluation and apoptosis inducing studies
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A new series of (E)-benzo[d]imidazol-2-yl)methylene)indolin-2-one derivatives has been synthesized and evaluated for their in vitro cytotoxic activity against a panel of selected human cancer cell lines of prostate (PC-3 and DU-145) and breast (BT-549, MDA-MB-231, MCF-7, 4T1), non-small lung (A549) and gastric (HGC) cancer cells along with normal breast epithelial cells (MCF10A). Among the tested compounds, 8l showed significant cytotoxic activity against MDA-MB-231 and 4T1 cancer cells with IC50values of 3.26 ± 0.24 μM and 5.96 ± 0.67 μM respectively. The compounds 8f, 8i, 8l and 8o were also screened on normal human breast epithelial cells (MCF10A) and found to be safer with lesser cytotoxicity. The treatment of MDA-MB-231 cells with 8l led to inhibition of cell migration ability through disruption of F-actin protein assembly. The flow-cytometry analysis reveals that the cells arrested in G0/G1 phase of the cell cycle. Further, the compound 8l induced apoptosis of MDA-MB-231 cells was characterized by different staining techniques such as Acridine Orange/Ethidium Bromide (AO/EB), DAPI, annexin V-FITC/PI, Rhodamine-123 and MitoSOX red assay. Western blot studies demonstrated that the compound 8l treatment led to activation of caspase-3, increased expression of cleaved PARP, increased expression of pro-apoptotic Bax and decreased expression of anti-apoptotic Bcl-2 in MDA-MB-231 cancer cells.
- Sharma, Pankaj,Thummuri, Dinesh,Reddy, T. Srinivasa,Senwar, Kishna Ram,Naidu,Srinivasulu, Gannoju,Bharghava, Suresh K.,Shankaraiah, Nagula
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p. 584 - 600
(2016/07/22)
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- Design and synthesis of 4′-O-alkylamino-tethered-benzylideneindolin-2-ones as potent cytotoxic and apoptosis inducing agents
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A series of new 4′-O-alkylamino-tethered-benzylideneindolin-2-one derivatives has been synthesized and evaluated for their anti-proliferative activity against selected human cancer cell lines of lung (A549), prostate (DU-145), breast (BT549 and MDA-MB-231) and normal breast epithelial cells (MCF-10A). Gratifyingly, the compounds 5j, 5o and 5r exhibited potent cytotoxicity against breast cancer cell lines (BT549 and MDA-MB-231) with IC50values in the range of 1.26–2.77?μM, and are found to be safer with lesser cytotoxicity on normal breast epithelial cells (MCF-10A). Further, experiments were conducted with these compounds 5j, 5o and 5r on MDA-MB-231 cancer cells to study the mechanism of growth inhibition and apoptosis inducing effect. Treatment of MDA-MB-231 cells with test compounds resulted in inhibition of cell migration through disorganization and disruption of F-actin capping protein. The flow-cytometry analysis results showed that the compound 5o arrested MDA-MB-231 cells in G0/G1 phase of cell cycle in a dose dependent manner. Hoechst staining study revealed that the test compounds inhibited tumor cell proliferation through induction of apoptosis. In addition, the mitochondrial membrane potential (DΨm) was affected and the increased level of reactive oxygen species (ROS) was noted in MDA-MB-231 cells.
- Senwar, Kishna Ram,Reddy, T. Srinivasa,Thummuri, Dinesh,Sharma, Pankaj,Bharghava, Suresh K.,Naidu,Shankaraiah, Nagula
-
supporting information
p. 4061 - 4069
(2016/08/01)
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- 1-chloroacetyloxindole(isatin) in reactions with some N-nucleophiles. Unexpetedly easy cleavage of chloroacetyl group
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Reactions of 1-chloroacetyloxindole and 1-chloroacetylisatin with some secondary amines, Girard’s reagent T and thiourea were studied. All investigated reactions proceeded via cleavage of the acyl group to form 3-substituted isatin or oxindole derivatives.
- Bogdanov,Kutuzova,Krivolapov,Dobrynin,Mironov
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p. 539 - 543
(2016/06/01)
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- Synthesis of diverse isatins: Via ring contraction of 3-diazoquinoline-2,4-diones
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An efficient synthesis of diverse isatin derivatives was accomplished by a copper-mediated reaction of 3-diazoquinoline-2,4-diones via ring contraction through domino Wolff rearrangement, decarboxylation, bromination, substitution, and dehydration. This protocol has several advantages as a one-pot procedure, with functional group tolerance, and high yield.
- Shrestha, Rajeev,Lee, Gun Joon,Lee, Yong Rok
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p. 63782 - 63787
(2016/07/19)
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- Divergent synthesis of indoles, oxindoles, isocoumarins and isoquinolinones by general Pd-catalyzed retro-aldol/α-arylation
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Divergent synthesis of indoles, oxindoles, isocoumarins and isoquinolinones is described in this report by using a general Pd-catalyzed tandem reaction of β-hydroxy carbonyl compounds with aryl halides bearing an ortho-nitro, -ester or -cyano substituent. A key retro-aldol/α-arylation reaction is involved that merges classic Pd cross-coupling chemistry with novel Pd-promoted retro-aldol C-C activation to produce α-arylated ketones or esters. Subsequent intramolecular condensation of the carbonyl with the ortho-synthon gives target heterocycles. The use of common, commercially available and cheap substrates and catalyst system adds additional synthetic advantages to the conceptual significance.
- Zhang, Song-Lin,Yu, Ze-Long
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supporting information
p. 10511 - 10515
(2016/11/18)
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- Palladium-Catalyzed C-H Activation and Cyclization of Anilides with 2-Iodoacetates and 2-Iodobenzoates: An Efficient Method toward Oxindoles and Phenanthridones
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A concise approach to the synthesis of oxindoles and phenanthridones from anilides is described. In the presence of catalytic amount of Pd(OAc)2, 2-iodoacetates and 2-iodobenzoates can be used to functionalize ortho C-H bond of anilides, which subsequently undergo intramolecular cyclization to give the products. A possible reaction mechanism that involves a PdII/PdIV catalytic cycle is proposed with the support of detailed mechanistic studies.
- Gandeepan, Parthasarathy,Rajamalli, Pachaiyappan,Cheng, Chien-Hong
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p. 1872 - 1879
(2016/06/15)
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- Design and synthesis of novel 3,5-substituted indolin-2-one derivatives
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In this paper, twelve novel 3,5-substituted indolin-2-one derivatives were designed and synthesized based on indolin-2-one. The structures of the new compounds have been confirmed by 1 H NMR, HR-MS and IR spectra analysis. This study provides a new method for development of indolin-2-one derivatives.
- Zhang, Yi-Ying,Liu, Yuan,Wang, Yu-Liang
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p. 491 - 495
(2015/02/05)
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- Synthesis, Biological, and Computational Evaluation of Novel 1,3,5-Substituted Indolin-2-one Derivatives as Inhibitors of Src Tyrosine Kinase
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Several substituted indolin-2-one derivatives were synthesized and evaluated for their activities against Src kinase. Several compounds showed activity against Src, with IC50 values in the low micromolar range. Among them, compound 2f showed the most significant activity with an IC50 value of 1.02 μM. Molecular docking studies have been performed for evaluation of the binding modes of compound 2f into the Src active site. The docking structure of compound 2f disclosed that the indole NH forms a hydrogen bond with the carbonyl of Met341. These results suggest that our novel compound 2f is a promising compound for the further development of indole-based drugs targeting Src kinase. A novel series of indole-2-one derivatives were synthesized and evaluated for their Src inhibitory activities. Compound 2f was found as the most promising compound with an IC50 value of 1.02 μM. Molecular docking studies were performed to disclose the binding mode for compound 2f.
- Kilic-Kurt, Zühal,Bakar, Filiz,?lgen, Süreyya
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p. 715 - 729
(2015/10/12)
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- A cinchona alkaloid catalyzed enantioselective sulfa-Michael/aldol cascade reaction of isoindigos: Construction of chiral bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters
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A cinchona alkaloid catalyzed diastereoselective and enantioselective sulfa-Michael/aldol cascade reaction between 1,4-dithiane-2,5-diol and isoindigos has been successfully developed to afford the highly congested bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters in high yields (up to 91%), excellent diastereoselectivities (up to >20 : 1 dr), and good enantioselectivities (up to 98% ee). Some synthetic transformations of the reaction products were also studied.
- Gui, Yong-Yuan,Yang, Jian,Qi, Liang-Wen,Wang, Xiao,Tian, Fang,Li, Xiao-Nian,Peng, Lin,Wang, Li-Xin
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p. 6371 - 6379
(2015/06/08)
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