- Revisiting ageless antiques; synthesis, biological evaluation, docking simulation and mechanistic insights of 1,4-Dihydropyridines as anticancer agents
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The historic DHP nucleus was serendipitously discovered by Arthur Hantzsch about 130 years ago and is still considered a hidden treasure for various pharmacological activities. Twenty-one DHP analogues were synthesized using the expedient one pot Hantzsch synthesis for screening as anticancer agents. Initially, the in vitro anti-proliferative single dose against a panel of 18 cancer cell lines showed that compounds 11b and 8f were the superlative candidates regarding their antitumor effect (GI% mean = 66.40% and 50.42%, correspondingly) compared to cisplatin (GI% mean = 65.58%) and doxorubicin (GI% mean = 74.56%). Remarkably, compound 11b showed a remarkable MDA-MB-468 anticancer activity (GI%=80.81%), higher than cisplatin (64.44%) and doxorubicin (76.72%), as well as strong antitumor activity against lung cancer A549 (GI%= 83.02%), more powerful than both cisplatin and doxorubicin. Compound 11b exhibited an exceptional anticancer activity against lung cancer cell line (A549) as its GI50 in nanomolar was (540 nM) with a 9-fold increase greater than cisplatin (GI50 = 4.93 μM) and with a selectivity index = 131 to cancer cells over normal cells. Further mechanistic investigations proved that DHPs anticipate simultaneously TOPI and RTKs (VEGFR-2, HER-2 and BTK) which can stimulate BAX/BAK and the executioner caspases via rtPCR studies.
- Sidhom, Peter A.,El-Bastawissy, Eman,Salama, Abeer A.,El-Moselhy, Tarek F.
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supporting information
(2021/06/21)
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- Design, synthesis, and molecular docking study of new monastrol analogues as kinesin spindle protein inhibitors
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Lung, colorectal, and breast cancers are the top three types of cancer by incidence and are responsible for one-third of the cancer incidence and mortality. A series of 18 3,4-dihydropyrimidine analogues bearing a 1,2-methylenedioxybenzene component at position 4 with diverse side chains at positions 5 and 6 was designed and synthesized as inhibitors of the Eg5 kinesin enzyme. Target compounds were screened for their anticancer activity according to the NCI-USA protocol toward a panel of 60 cancer cell lines. Compounds 12a and 12b displayed the best antiproliferation activity against many cell lines. Interestingly, compound 12a displayed lethal effects against non-small-cell lung cancer NCI-H522 cells (?42.26%) and MDA-MB-468 breast cancer cells (?1.10%) at a single-dose assay concentration of 10?5 M. Compounds 11c, 11d, 11g, 12a–d, 13, 15, and 18a were assayed against the kinesin enzyme, with IC50 values ranging from 1.2 to 18.71 μM, which were more potent compared with monastrol (IC50 = 20 μM). Cell cycle analysis of NCI-H522 cells treated with compound 12a showed cell cycle arrest at the G2/M phase. Furthermore, the expression levels of active caspase-3 and -9 were measured. A molecular docking study was performed for some demonstrative compounds as well as monastrol docked into the allosteric binding site of the kinesin spindle protein.
- El-Hamamsy, Mervat H.,Sharafeldin, Nabaweya A.,El-Moselhy, Tarek F.,Tawfik, Haytham O.
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- N, N’-dimethyl formamide (DMF) mediated Vilsmeier–Haack adducts with 1,3,5-triazine compounds as efficient catalysts for the transesterification of β-ketoesters
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N, N’-dimethyl formamide (DMF) mediated Vilsmeier–Haack (VH) adducts with 1,3,5-triazine compunds such as trichloroisocyanuric acid (TCCA) and trichlorotriazine (TCTA) were prepared by replacing classical oxy chlorides POCl3, and SOCl2, which were explored as efficient catalysts for the transesterification of β-ketoesters. The prepared (TCCA/DMF) and (TCTA/DMF) adducts improved greenery of the classical Vilsmeier–Haack reagents (POCl3/DMF), and (SOCl2/DMF), and demonstrated their better efficient catalytic ativity. Reaction times were in the range: 3.5 to 6.5 hr (SOCl2/DMF); 2.8–5.2 hr (POCl3/DMF); 2.5–5.2 hr (TCCA/DMF) and 2.5–5.0 hr (TCTA/DMF) catalytic systems. Ultrasonically (US) assisted protocols with these reagents further reduced the reaction times (two to three times), while microwave assisted (MW) protocols with these reagents were much more effective. The reactions could be completed in only few seconds (less than a minute) in MWassisted protocols as compared to US assited reactions, followed by good product yields.
- Chityala, Yadaiah,Duguta, Govardhan,Kamatala, Chinna Rajanna,Muddam, Bhooshan,Mukka, Satish Kumar
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p. 1641 - 1655
(2020/05/25)
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- 4-(Het)aryl-4,7-dihydroazolopyrimidines and Their Tuberculostatic Activity
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Structural analogs of a promising antituberculous agent, ethyl 5-methyl-7-(thiophen-2-yl)-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate have been synthesized by three-component condensations of various aromatic or hetaromatic aldehydes with several β-dicarbonyl compounds (CH acids) and 1H-1,2,4-triazol-5-amine or 1H-pyrazol-5-amine. The obtained compounds have been evaluated for tuberculostatic activity, and structure-activity relations have been analyzed.
- Titova, Yu. A.,Filatova,Fedorova,Rusinov,Charushin
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p. 775 - 781
(2019/08/02)
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- Design, synthesis, and bioactivity of dihydropyrimidine derivatives as kinesin spindle protein inhibitors
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A series of twenty-one 3,4-dihydropyrimidine derivatives bearing the heterocyclic 1,3-benzodioxole at position 4 in addition to different substituents at positions 2, 3 and 5 were designed and synthesized as monastrol analogs. The novel synthesized compounds were screened for their cytotoxic activity towards 60 cancer cell lines according to NCI (USA) protocol. Compounds 10b and 15 showed the best antitumor activity against most cell lines. Compound 15 was subsequently tested in 5-doses mode and displayed high selectivity towards CNS, prostate and leukemia subpanel with selectivity ratios of 22.30, 15.38 and 12.56, respectively at GI50 level. The IC50 of compounds 9d, 10b, 12, 15 and 16 against kinesin enzyme were 3.86 ± 0.12, 10.70 ± 0.35, 3.95 ± 0.12, 4.36 ± 0.14, and 14.07 ± 0.45 μM respectively, while the prototype compound, monastrol, reported IC50 value of 20 ± 0.42 μM. The safest compound among test compounds against normal cell line (HEK 293) is 10b with IC50 value of 62.02 ± 2.42 μM/ml in comparison to doxorubicin (IC50 = 11.34 ± 0.44 μM/ml). Cell cycle analysis of SNB-75 cells treated with compound 15 showed cell cycle arrest at G2/M phase. Further, the assay of levels of active caspase-3 and caspase-9 was investigated. Moreover, Molecular docking of compounds, 9d, 10b, 12, 15, 16, monastrol and mon-97 was performed to study the interaction between inhibitors and the kinesin spindle protein allosteric binding site.
- Tawfik, Haytham O.,El-Hamamsy, Mervat H.,Sharafeldin, Nabaweya A.,El-Moselhy, Tarek F.
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- General [4 + 1] Cyclization Approach to Access 2,2-Disubstituted Tetrahydrofurans Enabled by Electrophilic Bifunctional Peroxides
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A general [4 + 1] cyclization reaction of carbonyl nucleophiles with 2-iodomethylallyl peroxides, which function as unique electrophilic oxygen synthons, for the synthesis of a broad range of 2,2-disubstituted tetrahydrofurans is achieved under operationally simple conditions. The unprecedented asymmetric version of such reaction is also realized via chiral auxiliary-assisted cyclization, thus providing a distinct approach to access chiral tetrahydrofurans with high diastereoselectivities. The new method can be applied to the synthesis of core structure of posaconazole drug.
- Gao, Min,Zhao, Yukun,Zhong, Chen,Liu, Shengshu,Liu, Pengkang,Yin, Qi,Hu, Lin
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supporting information
p. 5679 - 5684
(2019/08/01)
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- NEW ANALOGS AS ANDROGEN RECEPTOR AND GLUCOCORTICOID RECEPTOR MODULATORS
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The present invention relates to novel dihydropyridine derivatives of formula (I): as modulators of nuclear receptors selected from androgen receptor and glucocorticoid receptor, to processes for their preparation, to pharmaceutical compositions comprising said compounds and to the use of said for manufacturing a medicament for the treatment of pathological conditions or diseases that can improve by modulation of androgen receptor and/or glucocorticoid receptor, selected from cancer, metastasizing cancers, benign prostate hyperplasia, polycystic ovary syndrome (PCOS), hair loss, hirsutism, acne, hypogonadism, muscle wasting diseases, cachexia, Cushing's syndrome, anti-psychotic drug induced weight gain, obesity, post-traumatic stress disorder and alcoholism.
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Paragraph 0194; 0195; 0201
(2019/05/16)
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- Design, Synthesis, and Anti-HIV-1 Evaluation of a Novel Series of 1,2,3,4-Tetrahydropyrimidine-5-Carboxylic Acid Derivatives
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A series of tetrahydropyrimidine derivatives (2a – 2l) were designed, synthesized, and screened for anti-HIV-1 properties based on the structures of HIV-1 gp41 binding site inhibitors, NB-2 and NB-64. A computational study was performed to predict the pharmacodynamics, pharmacokinetics, and drug-likeness features of the studied molecules. Docking studies revealed that the carboxylic acid group in the molecules forms salt bridges with either Lys574 or Arg579. Physiochemical properties (e.g., molecular weight, number of hydrogen bond donors, number of hydrogen bond acceptors, and number of rotatable bonds) of the synthesized compounds confirmed and exhibited that these compounds were within the range set by Lipinski's rule of five. Compounds 2e and 2k with 4-chlorophenyl substituent and 4-methylphenyl group at C(4) position of the tetrahydropyrimidine ring was the most potent one among the tested compounds. This suggests that these compounds may serve as leads for development of novel small-molecule HIV-1 inhibitors.
- Sepehri, Saghi,Soleymani, Sepehr,Zabihollahi, Rezvan,Aghasadeghi, Mohammad R.,Sadat, Mehdi,Saghaie, Lotfollah,Memarian, Hamid R.,Fassihi, Afshin
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- Development of selective inhibitors for the treatment of rheumatoid arthritis: (R)-3-(3-(Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile as a JAK1-selective inhibitor
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A series of 3(R)-aminopyrrolidine derivatives were designed and synthesized for JAK1-selective inhibitors through the modification of tofacitinib's core structure, (3R,4R)-3-amino-4-methylpiperidine. From the new core structures, we selected (R)-N-methyl-N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a scaffold for further SAR studies. From biochemical enzyme assays and liver microsomal stability tests, (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile (6) was chosen for further in vivo test through oral administration. Compound 6 showed improved selectivity for JAK1 compared to that of tofacitinib (IC50 11, 2.4 × 102, 2.8 × 103, and 1.1 × 102 nM for JAK1, JAK2, JAK3, and TYK2, respectively). In CIA and AIA model tests, compound 6 exhibited similar efficacy to tofacitinib citrate.
- Chough, Chieyeon,Joung, Misuk,Lee, Sunmin,Lee, Jaemin,Kim, Jong Hoon,Kim, B. Moon
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supporting information
p. 1495 - 1510
(2018/02/19)
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- Hypochlorite-Mediated Modulation of Photoinduced Electron Transfer in a Phenothiazine–Boron dipyrromethene Electron Donor–Acceptor Dyad: A Highly Water Soluble “Turn-On” Fluorescent Probe for Hypochlorite
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A highly water-soluble phenothiazine (PTZ)–boron dipyrromethene (BODIPY)-based electron donor–acceptor dyad (WS-Probe), which contains BODIPY as the signaling antennae and PTZ as the OCl? reactive group, was designed and used as a fluorescent chemosensor for the detection of OCl?. Upon addition of incremental amounts of NaOCl, the quenched fluorescence of WS-Probe was enhanced drastically, which indicated the inhibition of reductive photoinduced electron transfer (PET) from PTZ to 1BODIPY*; the detection limit was calculated to be 26.7 nm. Selectivity studies with various reactive oxygen species, cations, and anions revealed that WS-Probe was able to detect OCl? selectively. Steady-state fluorescence studies performed at varied pH suggested that WS-Probe can detect NaOCl and exhibits maximum fluorescence in the pH range of 7 to 8, similar to physiological conditions. ESI-MS analysis and 1H NMR spectroscopy titrations showed the formation of sulfoxide as the major oxidized product upon addition of hypochlorite. More interestingly, when WS-Probe was treated with real water samples, the fluorescence response was clearly visible with tap water and disinfectant, which indicated the presence of OCl? in these samples. The in vitro cell viability assay performed with human embryonic kidney 293 (HEK 293) cells suggested that WS-probe is non-toxic up to 10 μm and implicates the use of the probe for biological applications.
- Soni, Disha,Duvva, Naresh,Badgurjar, Deepak,Roy, Tapta Kanchan,Nimesh, Surendra,Arya, Geeta,Giribabu, Lingamallu,Chitta, Raghu
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supporting information
p. 1594 - 1608
(2018/06/26)
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- JANUS KINASE 1 SELECTIVE INHIBITOR AND PHARMACEUTICAL USE THEREOF
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Janus kinase 1 selective inhibitors and pharmaceutical use thereof are provided.
- -
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Paragraph 0289-0307
(2018/06/07)
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- Efficient synthesis and physicochemical characterization of natural danshensu, its S isomer and intermediates thereof
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The synthesis and molecular structure details of R- 3,4-dihydroxyphenyl lactic acid (danshensu) and related compounds, i.e. S isomer and the key intermediates have been described. Danshensu is an important water soluble phenolic acid of Salvia miltiorrhiza herb (danshen or red sag) with numerous applications in traditional Chinese medicine (TCM). Our synthetic approach was based on the Knoevenagel condensation of the protected 3,4-dihydroxybenzaldehyd and Meldrum acid derivative, followed by asymmetric Sharples dihydroxylation, reductive mono dehydroxylation and final deprotection. All compounds were characterized by various spectroscopic techniques: 1H-, 13C- magnetic resonance (NMR); Fourier-transformed infrared (FTIR); Raman, HR mass spectroscopy. For the determination of compound optical purities original HPLC methods were developed which allowed for the efficient resolution of danshensu R and S enantiomers as well as its intermediate enantiomers, using commercially available chiral stationary phases. Furthermore, in order to better understand danshensu specificity as a potential API in drug formulation, the physicochemical properties of the compounds were studied by thermal analysis, including differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA).
- Sidoryk, Katarzyna,Filip, Katarzyna,Cmoch, Piotr,?aszcz, Marta,Cybulski, Marcin
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p. 135 - 148
(2017/10/13)
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- Preparation of mesoporous carbon nitride materials using urea and formaldehyde as precursors and catalytic application as solid bases
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A series of mesoporous carbon nitride materials have been fabricated using inexpensive and eco-friendly urea and formaldehyde as precursors and mesocellular silica foam (MCF) as a template through a nanocasting approach. Several techniques, including XRD, TEM, elemental analysis, FT-IR, XPS, and CO2-TPD have been applied to characterize the physicochemical properties of the mesoCN materials, and the results show that the materials possess high surface areas (331–355?m2?g?1), relatively concentrated pore size of ca. 6?nm, and abundant and multiple nitrogen-containing species. As heterogeneous base catalysts, mesoCN materials demonstrate high catalytic activity and selectivity in both Knoevenagel condensation and transesterification reactions.
- Xu, Jie,Wang, Yue,Shang, Jie-Kun,Ma, Dan,Li, Yong-Xin
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p. 221 - 229
(2017/04/06)
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- Substituted heteroaryl compounds and compositions and uses thereof
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The invention provides a substituted ceteroary compound as well as a composition and a purpose thereof. The substituted ceteroary compound is a compound shown as a formula (I) or a stereoisomer, a tautomer, a nitrogen oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug of the pharmaceutically acceptable salt of the compound shown as the formula (I) and is used for regulating diseases or disorders mediated by one kind or various kinds of Janus kinase activities. The invention also provides a medicine composition containing the compound and a method of treating or alleviating the disease or disorder degree of a patient by inhibiting the Janus kinase activity.
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Paragraph 0462; 0463; 0464; 0465
(2018/01/04)
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- Comparative study on post-polymerization modification of C1 poly(benzyl 2-ylidene-acetate) and its C2 analog poly(benzyl acrylate)
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The present study investigates the challenging approach of post-polymerization modification on polymers with a sterically demanding reaction center. Therefore, the general possibility to functionalize polymethylene moieties was investigated. Poly(benzyl 2-ylidene-acetate) was synthesized by polymerization of benzyl 2-diazoacetate utilizing [(L-prolinate)RhI(1,5-dimethyl-1,5-cyclooctadiene)] as a catalyst. Subsequently, the modification of C1 polymerized poly(benzyl 2-ylidene-acetate) with amines was analyzed and the obtained data set was compared with experimental data derived for the C2 analog poly(benzyl acrylate). This is the first study on post-polymerization modification utilizing densely functionalized polymethylenes as starting materials.
- Krappitz, Tim,Theato, Patrick
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p. 686 - 691
(2016/02/09)
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- Catalytic synthesis method for higher beta-ketoester
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The invention relates to a reaction for synthesizing higher beta-ketoester by adopting NOMC (nitrogen-doped ordered mesoporous carbon) as a heterogeneous catalyst for catalyzing transesterification between simple beta-ketoester and alcohol. According to the reaction, NOMC is taken as the catalyst, beta-ketoester and alcohol are taken as the raw materials, the reaction is performed at the temperature of 90-110 DEG C for 4-6 h, and the highest yield of higher beta-ketoester can reach 97%. Compared with the conventional commonly-used homogeneous catalyst for the catalytic reaction, the reaction has the advantages that the catalyst is convenient to recover, the product is convenient to separate and the like.
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Paragraph 0031-0033
(2017/06/02)
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- Ag-Cu nanoparticles as efficient catalysts for transesterification of β-keto esters under acid/base-free conditions
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Transesterification of β-keto esters and alcohols are traditionally catalyzed by acid or basic catalysts. However, these traditional catalysts do not always meet the requirements of modern synthetic chemistry which need to be highly efficient, selective, and environmentally friendly. In this work, Ag-Cu metal sites were first introduced as transesterification catalysts. The effect of the support, Ag:Cu molar ratio, and reaction conditions were investigated. The Ag-Cu metal sites were proved to be active in the β-ketoester transesterification with various alcohols, having yields comparable to the conventional acid- or base-catalysts.
- Yue, Hongmei,Yu, Hao,Liu, Sheng,Xu, Chunli
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p. 19041 - 19051
(2016/03/01)
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- Decarboxylative Csp3-Csp3 coupling for benzylation of unstable ketone enolates: Synthesis of: P -(acylethyl)phenols
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A new decarboxylative Csp3-Csp3 coupling approach for the benzylation of ketone enolates has been developed. A variety of raspberry ketone derivatives were conveniently synthesized in good to excellent yields under mild conditions. A crossover reaction shed light on the mechanism of this tandem reaction.
- Wang, Sasa,Chen, Xinzheng,Ao, Qiaoqiao,Wang, Huifei,Zhai, Hongbin
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supporting information
p. 9454 - 9457
(2016/07/29)
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- Copper-catalyzed radical coupling of 1,3-dicarbonyl compounds with terminal alkenes for the synthesis of tetracarbonyl compounds
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A novel and efficient copper-catalyzed radical cross-coupling of 1,3-dicarbonyl compounds with terminal alkenes for the synthesis of tetracarbonyl compounds with a quaternary carbon atom has been developed. Mechanistically, this transformation involves the construction of two C-C bonds and two CO bonds in a one-pot process. The reaction tolerates a wide range of functional groups and proceeds under mild conditions.
- Zhang, Mei-Na,Zhao, Mi-Na,Chen, Ming,Ren, Zhi-Hui,Wang, Yao-Yu,Guan, Zheng-Hui
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supporting information
p. 6127 - 6130
(2016/05/19)
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- Enzymatic Synergism in the Synthesis of β-Keto Esters
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Reaction of alcohols with ethyl and tert-butyl acetoacetate catalyzed by a combination of commercially available enzymes is shown to be a convenient method for the preparation of a range of acetoacetic acid derivatives. Systematic studies proved that the combination of two or more enzymes enhances the yield of the reaction. Application of the selected enzyme mixture for enzymatic transesterification of various β-keto esters provided the respective products in excellent yields up to 96% and quantitative within 24 and 48 hours, respectively. The presented methodology is simple and mild, and can be used to prepare acetoacetates from primary and secondary alcohols. Application of a selected enzyme mixture for enzyme-catalyzed esterification of various carboxylic acids provided the respective β-hydroxy esters in excellent yields up to 96% and quantitative within 24 and 48 hours, respectively.
- Wisniewska, Catalina,Koszelewski, Dominik,Zysk, Malgorzata,Klossowski, Szymon,Zdlo, Anna,Brodzka, Anna,Ostaszewski, Ryszard
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p. 5432 - 5437
(2015/08/24)
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- Ester manufacturing method (by machine translation)
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PROBLEM TO BE SOLVED: To produce an ester compound by transesterification using an inexpensive and low toxic inorganic compound. SOLUTION: Transesterification of an ester compound and an alcohol compound is carried out under the presence of lanthanum nitrate (for example, lanthanum nitrate hexahydrate) and a phosphine compound (for example, tri-n-octylphosphine), thereby obtaining the ester product. For example, transesterification of dimethyl carbonate and benzyl alcohol is carried out under the presence of 1 mol% of lanthanum nitrate hexahydrate, and 2 mol% of tri-n-octylphosphine, thereby obtaining benzyl methylcarbonate at a yield of >99%. COPYRIGHT: (C)2012,JPO&INPIT
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Paragraph 0054; 0055; 0056
(2017/02/17)
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- Nano CuFe2O4: An efficient, magnetically separable catalyst for transesterification of β-ketoesters
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The preparation of a variety of β-ketoesters was achieved in high yields from methyl acetoacetate under neutral conditions through the utilization of magnetic CuFe2O4 nanoparticles as catalyst. Recycling of the catalyst was performed up to eight times without significant loss in activity. The catalyst was characterized using XRD, XPS, SEM and TEM techniques.
- Gohain, Mukut,Kumar, Vinod,Van Tonder, Johannes H.,Swart, Hendrik C.,Ntwaeaborwa, Odireleng M.,Bezuidenhoudt, Barend C. B.
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p. 18972 - 18976
(2015/03/04)
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- Straightforward access to the [3.2.2]nonatriene structural framework via intramolecular cyclopropenation/buchner reaction/cope rearrangement cascade
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A one-pot cascade process of benzyl enoldiazoacatates, initiated by dirhodium(II)-catalyzed intramolecular cyclopropene formation, occurs via a subsequent Buchner reaction and Cope rearrangement to provide straightforward access to bicyclo[3.2.2]nonatriene derivatives in high yields and selectivities.
- Xu, Xinfang,Wang, Xiangbo,Zavalij, Peter Y.,Doyle, Michael P.
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supporting information
p. 790 - 793
(2015/03/30)
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- Oxone-promoted hydration of electron-deficient allenic esters and ketones into 1,3-dicarbonyl compounds
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Abstract A novel and mild protocol for the hydration of electron-deficient allenic esters and ketones into various 1,3-dicarbonyl compounds is described. The hydration of allenes promoted by oxone in DMF afforded the corresponding products in moderate to good yields. This work features the employment of only a catalytic amount of inexpensive and nontoxic solid reagent oxone (2KHSO5·KHSO4·K2SO4), avoiding the utility of toxic metals or traditional Br?nsted acids, in a green version of viewpoint. A possible reaction mechanism for this transformation is also primarily proposed.
- Yi, Yu-Ping,Zheng, Yan,Nie, Jing,Ma, Jun-An
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supporting information
p. 4523 - 4526
(2015/06/30)
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- Enantioselective Mannich reaction of β-keto esters with aromatic and aliphatic imines using a cooperatively assisted bifunctional catalyst
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An efficient urea-enhanced thiourea catalyst enables the enantioselective Mannich reaction between β-keto esters and N-Boc-protected imines under mild conditions and minimal catalyst loading (1-3 mol %). Aliphatic and aromatic substituents are tolerated on both reaction partners, affording the products in good enantiomeric purity. The corresponding β-amino ketones can readily be accessed via decarboxylation without loss of enantiomeric purity.
- Neuvonen, Antti J.,Pihko, Petri M.
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supporting information
p. 5152 - 5155
(2015/01/08)
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- Prussian blue as an efficient catalyst for rate accelerations in the transesterification of β-ketoesters
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Prussian blue triggered transesterification of ethylacetoacetate with various alcohols underwent efficiently. The reaction is mild, eco-friendly, and selective with good yields. The proposed reaction pathway depicts the formation of an intermediate by the interaction of β-ketoesters with catalytic site of the Prussian blue, followed by nucleophilic attack of the alcohol at the electrophilic center followed by successive elimination of the proton to give the product. Observed longer reaction times under conventional conditions reduced amazingly under sonication and microwave irradiation followed enhanced yield of products.
- Srinivas,Rajanna,Krishnaiah,Kumar, M. Satish,Reddy, J. Narender
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p. 1212 - 1220
(2014/04/17)
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- General and efficient transesterification of β-keto esters with various alcohols using Et3N as a br?nsted base additive
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Transesterification of β-keto esters with a wide variety of allyl, benzyl, propargyl, and alkyl alcohols using, for the first time, commercially available and inexpensive Et3N as a Br?nsted base additive, is efficiently performed in toluene at reflux. The corresponding esters are exclusively obtained in 57-98% yields with no trace amounts of γ,δ-ketones, usually expected from the decarboxylative Carroll rearrangement.
- Mhasni, Olfa,Erray, Imen,Rezgui, Farhat
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p. 3320 - 3327
(2015/10/06)
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- Manganese(II) salts as efficient catalysts for chemo selective transesterification of β-keto esters under non-conventional conditions
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Transesterification of β-ketoesters with various alcohols has been studied under conventional and non-conventional conditions using desktop chemicals such as Mn(II) salts as catalysts. These methods offered transesterification of β-ketoesters in good yields with dramatic rate accelerations and reduced reaction times. The developed protocols under nonconventional methods such as sonication and microwave irradiation are highly promising compared with the existing procedures.
- Krishnaiah,Sandeep,Kondhare,Rajanna,Narendar Reddy,Rajeshwar Rao,Zhubaidha
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p. 703 - 706
(2013/02/23)
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- Highly regioselective organocatalyzed synthesis of pyrazoles from diazoacetates and carbonyl compounds
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A general, organocatalytic inverse-electron-demand [3+2] cycloaddition reaction between a range of carbonyl compounds and diazoacetates has been developed. This reaction is catalyzed by secondary amines as a "green promoter" to generate substituted pyrazoles with high levels of regioselectivity. It is noteworthy that this [3+2] cycloaddition reaction proceeds efficiently at room temperature with a simple and inexpensive catalyst. Considering the large variety and ready availability of the starting materials (e.g. ketones, β-ketoesters, β-diketones, and aldehydes), as well as the operational simplicity of this process, a convenient, practical, and highly modular pyrazole synthesis has been developed. We believe that this work will arouse more research interest in the organocatalytic synthesis of other biologically active heterocycles. Such studies are currently underway in our laboratory. Dipoles apart: In situ formed enamines react with diazoacetates under mild conditions to afford the corresponding polysubstituted pyrazoles in good-to-excellent yields through an inverse-electron-demand 1,3-dipolar cycloaddition process (see scheme). Copyright
- Wang, Lei,Huang, Jiayao,Gong, Xiaojie,Wang, Jian
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supporting information
p. 7555 - 7560
(2013/07/05)
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- An efficient synthesis of β-ketoesters via transesterification and its application in Biginelli reaction under solvent-free, catalyst-free conditions
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A simple and efficient transesterification process for the synthesis of β-ketoester derivatives has been achieved by the reaction of methyl β-ketoester with higher alcohols at 110 C under solvent-free, catalyst-free conditions and its application in synthesis of 3,4-dihydropyrimidin-2(1H)-ones C-5 ester derivatives via Biginelli reaction has been described.
- Dharma Rao,Acharya,Kaushik
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supporting information
p. 6644 - 6647
(2013/11/19)
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- AgOTf-catalyzed transesterification of β-keto esters
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AgOTf proved to be an effective catalyst for the transesterification of β-keto esters with primary, secondary and tertiary alcohols. The products were obtained in high yield within a reasonable reaction time period. The kinetics of the transesterification reaction were also studied and the reaction was found to follow second-order kinetics. Copyright
- Das, Rima,Chakraborty, Debashis
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experimental part
p. 140 - 144
(2012/05/20)
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- In situ generated "lanthanum(iii) nitrate alkoxide" as a highly active and nearly neutral transesterification catalyst
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In situ generated lanthanum(iii) nitrate alkoxide is a highly active and nearly neutral transesterification catalyst, which can promote non-epimerized transesterification of α-substituted chiral carboxylic esters under reflux conditions.
- Hatano, Manabu,Kamiya, Sho,Ishihara, Kazuaki
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supporting information
p. 9465 - 9467
(2012/10/29)
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- Design and synthesis of new 1,4-dihydropyridines containing 4(5)-chloro-5(4)-imidazolyl substituent as a novel calcium channel blocker
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New analogues of nifedipine, in which the ortho-nitro phenyl group at position 4 has been replaced by 4(5)-chloro-5(4)-imidazolyl substituent and which are able to interact with the receptor by hydrogen binding were designed, synthesized, and evaluated as calcium channel antagonists. The designed dihydropyridines were synthesized using the Hantzsch condensation and evaluated as calcium channel antagonists using the high K+ contraction of guineapig ileal longitudinal smooth muscle. A docking study was performed using the AutoDock4 program, and QSAR equations were obtained using multilinear regression. Our computational studies indicated that the oxygen of the ester (O10) and the N3′ of the imidazole ring form a hydrogen bonding interaction with the NH of HIS 363 and NH of LYS354, respectively, and that the sum of the BEHp5 and RDF075p are the most significant descriptors. The results of calcium channel antagonist evaluation demonstrated that increasing the chain length in C3 and C5 ester substituents increased activity. The most potent compound was the bis-phenylpropyl ester (5l) derivative, in that it was more active than the reference drug nifedipine and that the bis-phenylethyl ester (5k) derivative had comparable activity with nifedipine. The present research revealed that the 4(5)-chloro-5(4)-imidazolyl moiety is a bioisoster of o-nitrophenyl in nifedipine and provided novel dihydropyridines with more activity as calcium channel antagonists.
- Iman, Maryam,Davood, Asghar,Nematollahi, Ali Reza,Dehpoor, Ahmad Rerza,Shafiee, Abbas
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experimental part
p. 1417 - 1426
(2012/05/04)
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- 6 - METHYL - 4 - PHENYL - 5 - ( PHENYL OR CYCLOALKYL) CARBAMOYL - 1,2,3, 4 - TETRAHYDROPYRIMIDIN- 2 - ONE DERIVATIVES AS ANTITUBERCULAR AGENTS
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The present invention discloses antitubercular compounds selected from tetrahydropyrimidones/ tetrahydrothiopyrimidone derivatives of Formula (1) and its pharmaceutically acceptable salts for the treatment of Mycobacterium in the dormant phase. Formula (1) wherein, R is H, halogen, dihalogen, O-alkyl, di- O-alkyl, R1 is phenyl, chlorophenyl, nitrophenyl, diclorophenyl, cycloalkyl, preferably cyclohexyl, X is O or S.
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Page/Page column 12; 15
(2011/12/14)
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- Bismuth(III) chloride-catalyzed highly efficient transesterification of β-keto esters
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Bismuth(III) chloride was found to be an efficient catalyst for the transesterification of a variety of β-keto esters with a wide range of alcohols to afford transesterified products in good to high yields in short reaction times (see Table). Copyright
- Sabitha, Gowravaram,Srinivas, Rangavajjula,Gopal, Peddabuddi,Bhikshapathi,Yadav, Jhillu Singh
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experimental part
p. 119 - 121
(2011/03/17)
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- Efficient trans-acetoacylation mediated by ytterbium(III) triflate as a catalyst under solvent-free condition
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A simple and efficient trans-acetoacylation method for the synthesis of β-keto ester derivatives has been described using ytterbium(III) triflate as a new catalyst under solvent-free condition. This method was found to be efficient and convenient for the synthesis of a wide variety of β-keto ester derivatives.
- Dharma Rao,Kaushik
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experimental part
p. 5104 - 5106
(2011/10/08)
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- Molecular iodine in ionic liquid: A green catalytic system for esterification and transesterification
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Esterification of carboxylic acids and transesterification of-ketoesters with alcohols have been developed using a catalytic amount of iodine in polyethylene glycol (PEG) ionic liquid (IL 1000) to afford the corresponding esters in good yields. By simple separation of the ionic-liquid phase containing the iodine, the system of I2/IL 1000 can be reused several times. Copyright
- Ren, Yiming,Cai, Chun
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scheme or table
p. 1670 - 1676
(2010/08/03)
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- BF3OEt2: An efficient catalyst for transesterification of β-ketoesters
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A facile and selective transesterification of β-ketoesters using BF3OEt2 as catalyst is described. The emphasis has been placed on the reaction of methyl acetoacetate with a series of alcohols of different structures, leading in all cases to good to excellent yields.
- Yang, Jinhui,Ji, Congbin,Zhao, Yanmin,Li, Yunfeng,Jiang, Shizhi,Zhang, Zhiwei,Ji, Yongqiang,Liu, Wanyi
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experimental part
p. 957 - 963
(2010/06/12)
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- Solution versus fluorous versus solid-phase synthesis of 2,5-disubstituted 1,3-azoles. Preliminary antibacterial activity studies
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(Chemical Equation Presented) A small library of compounds with an oxa(thia)zole scaffold and structural diversity in both positions 2 and 5 has been synthesized. Double acylation of a protected glycine affords intermediate α-amido-β-ketoesters, which in turn can be dehydrated to afford 1,3-oxazoles or reacted with Lawesson's reagent to furnish 1,3-thiazoles. This procedure was designed with its adaptation to fluorous techniques in mind. Thus, when a protected glycine with a fluorous tag in the ester moiety is used as a starting material, the synthesis can be easily completed without column chromatography purification of intermediate compounds with good to excellent yields, thus affording a suitable entry to the preparation of small libraries of these bioactive compounds. The prepared oxa(thia)zoles were assayed for their antibacterial activity, and several of them were active against Staphylococcus aureus.
- Sanz-Cervera, Juan F.,Blasco, Rauel,Piera, Julio,Cynamon, Michael,Ibanez, Ignacio,Murguia, Marcelo,Fustero, Santos
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scheme or table
p. 8988 - 8996
(2010/03/24)
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- SUBSTITUTED HETEROCYCLIC COMPOUNDS
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The present invention relates to novel heterocyclic compounds and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula (I): wherein Q1, Q2, R2, R3, R4, R5, and R6 are as described herein. The invention also relates to methods for the preparation of the compounds, and to pharmaceutical compositions containing such compounds.
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Page/Page column 17-18
(2009/01/23)
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- Boric acid: an efficient and environmentally benign catalyst for transesterification of ethyl acetoacetate
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An efficient and environmentally benign boric acid catalyzed protocol for the transesterification of ethyl acetoacetate with a variety of primary and secondary alcohols in good to excellent yields is described. The versatility of this transformation is demonstrated with problematic substrates such as propargyl alcohol and allyl alcohol, which are known to undergo Carroll rearrangement during transesterification.
- Kondaiah,Reddy, L. Amarnath,Babu, K. Srihari,Gurav,Huge,Bandichhor,Reddy, P. Pratap,Bhattacharya,Anand, R. Vijaya
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p. 106 - 109
(2008/04/13)
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- Zwitterionic salts as mild organocatalysts for transesterification
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(Chemical Equation Presented) The exothermic reaction of 3,5-bis(trifluoromethyl)phenyl or 4-nitrophenyl isothiocyanate with 4-pyrrolidinopyridine (PPY) gave the corresponding arylaminothiocarbonylpyridinium salts in quantitative yields. These novel zwitterionic salts were effective as organocatalysts for the transesterification reaction of an equimolar mixture of methyl carboxylates and alcohols in hydrocarbons such as heptane and octane under azeotropic reflux conditions with the removal of methanol. In sharp contrast, PPY was inert as a catalyst under the same reaction conditions.
- Ishihara, Kazuaki,Niwa, Masatoshi,Kosugi, Yuji
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supporting information; experimental part
p. 2187 - 2190
(2009/05/27)
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- Copper-promoted cycloaddition of diazocarbonyl compounds and acetylides
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(Chemical Equation Presented) HOMO-logous: The copper-mediated cycloaddition of alkynes with diazo carbonyl compounds to give pyrazoles is reminiscent of the copper-catalyzed cycloaddition of alkynes and azides. The formation of the copper acetylide is proposed to narrow the energy gap between the highest occupied molecular orbital (HOMO) of the alkyne and the lowest unoccupied molecular orbital (LUMO) of the diazo compound.
- Qi, Xiangbing,Ready, Joseph M.
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p. 3242 - 3244
(2008/02/13)
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- Hexamethylenetetramine-mediated transesterification of β-keto esters
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Treatment of methyl or ethyl β-keto esters with primary, secondary, or tertiary alcohols in the presence of a catalytic amount of hexamethylenetetramine results in good to high yields of the corresponding esters. Georg Thieme Verlag Stuttgart.
- Ribeiro, Rodrigo S.,De Souza, Rodrigo O. M. A.,Vasconcellos, Mario L. A. A.,Oliveira, Bianca L.,Ferreira, Leonardo C.,Aguiar, Lucia C. S.
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- A mild and regioselective method for α-bromination of β-keto esters and 1,3-diketones using bromodimethylsulfonium bromide (BDMS)
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Bromodimethylsulfonium bromide has been found to be an effective and regioselective reagent for α-monobromination of β-keto esters and 1,3-diketones. A wide variety of β-keto esters and 1,3-diketones undergo chemoselective α-monobromination with excellent yields at 0-5 °C or room temperature. The notable advantages of this protocol are no need of chromatographic separation, use of less hazardous reagent than molecular bromine, and no added base, Lewis acid, or other catalyst.
- Khan, Abu T.,Ali, Md. Ashif,Goswami, Papori,Choudhury, Lokman H.
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p. 8961 - 8963
(2007/10/03)
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- Microwave assisted rapid and efficient synthesis of aryl methyl ketones and β-keto esters using Meldrum's acid
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Microwave mediated rapid and efficient synthesis of aryl methyl ketones and β-keto esters from acyl Meldrum's acid by hydrolysis and alcoholysis, respectively, has been reported.
- More,Mahulikar
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p. 823 - 825
(2007/10/03)
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- Structure-activity relationship study of 1,4-dihydropyridine derivatives blocking N-type calcium channels
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Cilnidipine is a 1,4-dihydropyridine derived L/N-type calcium channel dual blocker possessing neuroprotective and analgesic effects which are related to its N-type calcium channel inhibitory activity. In order to find specific N-type calcium channel blockers with the least effects on cardiovascular system, we performed structure-activity relationship study on APJ2708, which is a derivative of cilnidipine, and found a promising N-type calcium channel blocker 21b possessing analgesic effect in vivo with a 1600-fold lower activity against L-type calcium channels than that of cilnidipine.
- Yamamoto, Takashi,Niwa, Seiji,Ohno, Seiji,Onishi, Tomoyuki,Matsueda, Hiroyuki,Koganei, Hajime,Uneyama, Hisayuki,Fujita, Shin-Ichi,Takeda, Tomoko,Kito, Morikazu,Ono, Yukitsugu,Saitou, Yuki,Takahara, Akira,Iwata, Seinosuke,Shoji, Masataka
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p. 798 - 802
(2007/10/03)
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- Facile and selective transesterification of β-keto esters using NaIO4, KIO4, and anhydrous CaCl2 as inexpensive catalysts under neutral conditions
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NaIO4, KIO4 and anhydrous CaCl2 catalyzed selective transesterification of β-keto esters is described. Neutral reaction conditions and inexpensive catalysts are important features of this method.
- Bandgar, Babasaheb P.,Hashmi, Arshad M.,Pandit, Shivaji S.
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p. 1101 - 1104
(2007/10/03)
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- Niobium(V) oxide: A new and efficient catalyst for the transesterification of β-keto esters
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Niobium(V) oxide is an efficient catalyst for the transesterification of β-keto esters with several kinds of alcohols, leading to good conversions. Moderate to good isolated product yields have been obtained at faster rates than those recently reported for various catalysts.
- De Sairre, Mirela Inês,Bronze-Uhle, érika Soares,Donate, Paulo Marcos
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p. 2705 - 2708
(2007/10/03)
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