- Solvolytic Elimination and Hydrolysis promoted by an Aromatic Hydroxy-group. Part 2. The Hydrolysis of 2-Bromo-4-dibromomethylphenol in 95percent 1,4-Dioxane
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The reaction of 2-bromo-4-dibromomethylphenol with water in slightly aqueous (95percent) 1,4-dioxane has been examined kinetically by using u.v. spectroscopy, which provides evidence for the transient formation of the quinone methide, 2-bromo-4-bromomethylenecyclohexa-2,5-dienone, during the hydrolysis.The final product is 3-bromo-4-hydroxybenzaldehyde.The rate of disappearance of starting material is independent of acidity, but is reduced by added or developing bromide ion.The rate of the loss of bromide ion from the phenol is very much greater than that of the corresponding reaction of 2-bromo-4-dibromomethylanisole under the same conditions.An estimate of the value of ?p-OH+ (-1.36), made by using these relative rates, is larger than the value (-0.92) based on relative rates of aromatic electrophilic substitution.Solvent kinetic isotope effects on these reactions are reported; the theoretical implications of variation in the substituent parameter for the hydroxy-group is discussed in terms of solvent effects on H-O hyperconjugation.
- Mare, Peter B. D. de la,Newman, Paul A.
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Read Online
- Synthesis of magnaldehydes B and e and dictyobiphenyl B by microwave-promoted cross-coupling of boronophenols
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Magnaldehydes B and E along with their 4′-methylated derivatives are naturally occurring 2,4′-biphenols that have been isolated from the Magnoliaceae. Herein, these natural products have been synthesized from a common intermediate, which was obtained by a microwave-promoted, heterogeneously catalyzed, and protecting-group-free Suzuki-Miyaura coupling reaction in an aqueous medium. These reaction conditions were also successfully applied to a one-step synthesis of the slime mold metabolite dictyobiphenyl B. A protecting-group-free Suzuki-Miyaura cross-coupling reaction of halophenols and boronophenols by using Pd/C as the catalyst and water as the solvent under microwave irradiation has been used for the synthesis of five biphenol-type natural products.
- Schmidt, Bernd,Riemer, Martin
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Read Online
- Ni-NiO heterojunctions: a versatile nanocatalyst for regioselective halogenation and oxidative esterification of aromatics
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Herein, we report a facile method for the synthesis of Ni-NiO heterojunction nanoparticles, which we utilized for the nuclear halogenation reaction of phenol and substituted phenols usingN-bromosuccinimide (NBS). A remarkablepara-selectivity was achieved for the halogenated products under semi-aqueous conditions. Interestingly, blocking of thepara-position of phenol offeredortho-selective halogenation. In addition, the Ni-NiO nanoparticles catalyzed the oxidative esterification of carbonyl compounds with alcohol, diol or dithiol in the presence of a catalytic amount of NBS. It was observed that the aromatic carbonyls substituted with an electron-donating group favoured nuclear halogenation, whereas an electron-withdrawing group substitution in carbonyl compounds facilitated the oxidation reaction. In addition, the catalyst was magnetically separated and recycled 10 times. The tuned electronic structure at the Ni-NiO heterojunction controlled selectivity and activity as no suchpara-selectivity was observed with commercially available NiO or Ni nanoparticles.
- Bhardwaj, Nivedita,Goel, Bharat,Indra, Arindam,Jain, Shreyans K.,Singh, Ajit Kumar,Tripathi, Nancy
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p. 14177 - 14183
(2021/08/16)
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- THERAPY
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The invention addresses radioresistance in cancer treatment involving radiotherapy and, in particular, limitations associated with the use of the drug sulfasalazine. Specifically, it provides a series of compounds for use as radiosensitizers in the treatment of cancers such as glioblastomas which are lethal and inherently resistant to radiotherapy, in one embodiment, the invention provides compounds of general formula (I), their stereoisomers and pharmaceutically acceptable salts for use as radiosensitizers in the treatment of cancer wherein ring A is selected from optionally substituted phenyl, biphenyl and fluorenyl; each X is independently selected from: -C1-6 alkyl (preferably C1-3 alkyl, e.g. -CH3), -O-C1-6 alkyl (preferably -O-C1-3 alkyl, e.g, -OCH3), -S-C1-6 alkyl (preferably -S-C1-3 alkyl, e.g, -SCH3), -OH, -SH, -CO2R1 (where R1 is H or C1-6 alkyl, preferably C1-3 alkyl, e.g. -CH3), -SO2-C1-6 alkyl (preferably -SO2-C1-3 alkyl, e.g. -SO2-CH3), -SO2-NR2R3 (where R2 is H and R3 is optionally substituted phenyl), -NR4R5 (wherein R4 and R5 are independently selected from H, C1-6 alkyl (preferably C1-3 alkyl, e.g. -CH3), and -CO-C1-6 alkyl (preferably -CO-C1-3 alkyl, e.g. -CO-CH3), halogen (e.g. F, Cl or Br), and optionally substituted tetrazolyl; n is an integer from 0 to 5, preferably 0 to 2, e.g. 1 or 2; and denotes an E or Z double bond.
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Page/Page column 25
(2021/04/02)
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- Structure-Activity-Relationship-Aided Design and Synthesis of xCT Antiporter Inhibitors
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The xCT antiporter is a cell membrane protein involved in active counter-transportation of glutamate (outflux) with cystine (influx) over the human cell membrane. This feature makes the xCT antiporter a crucial element of the biosynthesis of the vital free radical scavenger glutathione. The prodrug sulfasalazine, a medication for the treatment of ulcerative colitis, was previously proven to inhibit the xCT antiporter. Starting from sulfasalazine, a molecular scaffold jumping followed by SAR-assisted design and synthesis provided a series of styryl hydroxy-benzoic acid analogues that were biologically tested in vitro for their ability to decrease intracellular glutathione levels using four different cancer cell lines: A172 (glioma), A375 (melanoma), U87 (glioma) and MCF7 (breast carcinoma). Depletion of glutathione levels varied among the compounds as well as among the cell lines. Flow cytometry using propidium iodide and the annexin V marker demonstrated minimal toxicity in normal human astrocytes for a promising candidate molecule (E)-5-(2-([1,1′-biphenyl]-4-yl)vinyl)-2-hydroxybenzoic acid.
- Cirillo, Davide,Sarowar, Shahin,?yvind Enger, Per,Bj?rsvik, Hans-René
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p. 2650 - 2668
(2021/06/01)
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- Herbicide based on haloxyfop, flumetsulam and halosulfuron-methyl
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The invention discloses a herbicide based on haloxyfop, flumetsulam and halosulfuron-methyl. The herbicide is prepared from the following raw materials in parts by weight: 1-15 parts of haloxyfop-R-methyl, 1-15 parts of flumetsulam, 1-37 parts of halosulfuron-methyl, 1-2 parts of a modified antioxidant, 10-12 parts of borax, 6-8 parts of a surfactant, 10-12 parts of triethanolamine, 10-12 parts of vegetable oil and 40-42 parts of deionized water. After the haloxyfop-R-methyl, the flumetsulam and the halosulfuron-methyl are mixed, the effects are complementary, the weeding spectrum is wider, the weeding activity is high, the weeding effect is more excellent. In addition, the modified antioxidant is added into the herbicide formula, so that the composite herbicide has the effects of resisting oxidation aging and ultraviolet aging, effective components are prevented from decomposing and losing efficacy in the presence of light, the pesticide effect is kept lasting, and the application prospect and popularization value are remarkably improved.
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Paragraph 0038; 0045; 0053; 0060; 0068; 0075
(2021/06/21)
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- Preparation method of 3-bromo-4-hydroxybenzaldehyde
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The invention discloses a preparation method of 3-bromo-4-hydroxybenzaldehyde. The preparation method comprises the following steps: (1) carrying out a bromination reaction on p-hydroxybenzene methylal and bromine to obtain 3-bromo-4-hydroxybenzene methylal; and (2) carrying out a hydrolysis reaction on the 3-bromo-4-hydroxybenzene methylal obtained in the step (1), and carrying out post-treatmentafter the reaction is finished to obtain the 3-bromo-4-hydroxybenzaldehyde. According to the preparation method, aldehyde is replaced with acetal for the bromination reaction, so that generation of adibromo product is effectively avoided, the yield and purity of a monobromo product are improved, and industrialization is facilitated.
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Paragraph 0036; 0041; 0042
(2020/02/19)
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- A novel class of selective CK2 inhibitors targeting its open hinge conformation
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Protein kinase CK2 sustains cancer growth, especially in hematological malignancies. Its inhibitor SRPIN803, based on a 6-methylene-5-imino-1,3,4-thiadiazolopyrimidin-7-one scaffold, showed notable specificity. Our synthesis of the initially proposed SRPIN803 resulted in its constitutional isomer SRPIN803-revised, where the 2-cyano-2-propenamide group does not cyclise and fuse to the thiadiazole ring. Its crystallographic structure in complex with CK2α identifies the structural determinants of the reported specificity. SRPIN803-revised explores the CK2 open hinge conformation, extremely rare among kinases, also interacting with side chains from this region. Its optimization lead to the more potent compound 4, which inhibits endocellular CK2, significantly affects viability of tumour cells and shows remarkable selectivity on a panel of 320 kinases.
- Battistutta, Roberto,Cazzanelli, Giulia,Dalle Vedove, Andrea,Demitri, Nicola,Lolli, Graziano,Ongaro, Alberto,Ribaudo, Giovanni,Ruzzene, Maria,Sarno, Stefania,Zagotto, Giuseppe,Zanforlin, Enrico,Zonta, Francesca
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supporting information
(2020/04/15)
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- NOVEL HETEROCYCLIC COMPOUNDS AS IRAK4 INHIBITORS
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The present invention relates to novel compounds of the general formula (I) their tautomeric forms, their enantiomers, their diastereoisomers, their pharmaceutically accepted salts, or pro-drugs thereof, which are useful for the treatment or prevention of cancer and inflammatory diseases associated with Interleukin-1 Receptor Associated Kinase (IRAK), and more particularly compounds that modulate the function of IRAK4.
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Page/Page column 27
(2019/06/23)
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- Magnetic nano-structured cobalt-cobalt oxide/nitrogen-doped carbon material as an efficient catalyst for aerobic oxidation of p-cresols
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Efficient aerobic oxidation has been developed for the selective preparation of a sequence of valuable p-hydroxybenzaldehydes from corresponding p-cresols, using a new magnetically separable catalyst of nano-structured cobalt-cobalt oxide/nitrogen-doped carbon (CoOx@CN) material. CoOx@CN showed high activity for the 2-methoxy-4-cresol oxidation to vanillin, giving great yield (90%) and with good turnover number (210), as well as other p-cresols in good to great yields. The catalytic performance was investigated and related to the structural, chemical and magnetic properties which determined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FT-IR) and vibrating sample magnetometer (VSM). The effects of base to substrate molar ratio, catalyst concentration, temperature, and solvent on the conversion and selectivity patterns also have been studied. The investigation revealed that remarkable catalytic properties of CoOx@CN could be ascribed to the active species cobalt oxide, doped nitrogen and porous carbon with large surface area. The size of the catalyst is a key factor for catalyst performance. The ferromagnetic property of catalyst enables to recycle easily by an external magnetic field and reuse six successive times without significant activity loss.
- Liang, Cheng,Li, Xuefeng,Su, Diefeng,Ma, Qiyi,Mao, Jianyong,Chen, Zhirong,Wang, Yong,Yao, Jia,Li, Haoran
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p. 121 - 131
(2018/05/22)
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- Design, synthesis and biological evaluation of 1-hydroxy-2-phenyl-4-pyridyl-1H-imidazole derivatives as xanthine oxidase inhibitors
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In our previous study, we reported a series of 1-hydroxy-2-phenyl-1H-imidazole-5-carboxylic acid derivatives that presented excellent in vitro xanthine oxidase inhibitory potency. As a continuation study, a series of 1-hydroxy-2-phenyl-1H-imidazole derivatives containing a pyridine moiety (4a-g and 5a-g) at the 4-position was designed and synthesized. Evaluation of in vitro xanthine oxidase inhibition demonstrated that the 4a-g series was more potent than the 5a-g series. Compound 4f was the most promising derivative in the series with an IC50 value of 0.64 μM. A Lineweaver-Burk plot revealed that compound 4f acted as a mixed-type xanthine oxidase inhibitor. An iso-pentyloxy group at the 4′-position improved the inhibitory potency. More interestingly, structure-activity relationship analysis indicated that the pyridine para-N atom played a crucial role in the inhibition. Molecular modeling provided a reasonable explanation for the structure-activity relationships observed in this study. In addition, a three dimensional quantitative structure-activity relationships model which possessed reasonable statistics (q2 = 0.885 and r2 = 0.993) was conducted to further understand the structural basis of these compounds as xanthine oxidase inhibitors. These compounds, especially compound 4f, have good potential for further investigations.
- Zhang, Tingjian,Lv, Yunying,Lei, Yu,Liu, Dan,Feng, Yao,Zhao, Jiaxing,Chen, Shaolei,Meng, Fanhao,Wang, Shaojie
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p. 668 - 677
(2018/02/09)
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- Ultrasonically assisted halogenation of aromatic compounds using isoquinolinium bound hypervalent chromium and tetrabutylammonium halides in PEG-600 solutions under acid free and solvent-free conditions
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Isoquinolinium bound Cr(VI) reagents like isoquinolinium dichromate (IQDC) and isoquinolinium chlorochromate (IQCC) have been successfully accomplished as efficient reagents for oxidative halogenation of aromatic compounds using tetrabutylammonium halide (TBAX) as halogenating agents in aqueous polyethylene glycol (PEG-600) under acid free conditions. Tetrabutylammonium bromide (TBAB) has been used for bromination and tetrabutylammonium iodide (TBAI) for iodination. The halogenation reactions that occurred smoothly in 2 to 7 h under conventional conditions are accelerated magnificently under sonication with few minutes (25 to 70 min) of reaction time and fairly good yields. The reactions occurred at moderate temperature under mild and environmentally safe conditions with simple work up.
- Sambashiva Rao,Ramesh, Kola,Rajanna,Chakrvarthi
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p. 1892 - 1896
(2018/07/10)
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- Novel synthetic process of isovanillin
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The invention discloses a novel synthetic process of isovanillin, and relates to the field of organic synthesis technology. The method comprises: reacting 4-hydroxybenzaldehyde as a raw material with bromine to obtain 3-bromo 4-hydroxybenzaldehyde, reacting with methyl iodide to obtain 3-bromo-4-methoxy benzaldehyde, and then performing hydrolysis to obtain the isovanillin under the action of sodium hydroxide and cuprous chloride. The method adopts cheap and easily obtained 4-hydroxybenzaldehyde as the starting material, the isovanillin is obtained under mild reaction conditions, and the economic efficiency of a process is improved while the cost is reduced. The total yield of the product, isovanillin, obtained by using the optimum process is up to 64.1%, the conversion rates of the raw materials in each step are significantly increased, and the method is suitable for industrial production.
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Paragraph 0015; 0030; 0034; 0038; 0042; 0046
(2017/09/18)
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- Bismuth trichloride–mediated cleavage of phenolic methoxymethyl ethers
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A simple and efficient method for removal of phenolic methoxymethyl ethers in the presence of 30?mol% of bismuth trichloride in acetonitrile/water is described. Notable features of the cleavage protocol entail use of an ecofriendly bismuth reagent, ease of handling, low cost, operational simplicity, and good functional group compatibility. A number of structurally varied phenolic methoxymethyl ethers were cleaved in good to excellent yields.
- Obaro-Best, Oghale,Reed, Jack,Norfadilah, Alya A. F. B.,Monahan, Ryan,Sunasee, Rajesh
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supporting information
p. 586 - 593
(2016/06/08)
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- Role of alkali in catalytic oxidation of p-cresols
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The investigation of alkali acting as the key component during the liquid-phase catalytic oxidation of p-cresols to p-hydroxyl aromatic aldehydes is far from satisfied, thus a detailed exploration is presented. It was observed that the p-cresols were activated by alkali to form phenolate salt to ensure mild reaction conditions demonstrated by comparing the oxidation of p-cresol and its phenolate sodium. It was also found that excess alkali improved the selectivity of aldehyde by inhibiting the formation of dimeric side products in view of an analysis of the side products distribution. The alkaline alcoholic anion facilitates the 1,6-addition reaction between p-benzoquinone methide and solvent. Thus, more alkali was needed in solvents with high pKa values and high water content. The detection of trace acid during the oxidation of p-cresols suggested the phenoxy radical mechanism rather than the classic benzyl radical mechanism proposed for interpreting the oxidation of non-hydroxyl aromatic hydrocarbons. These conclusions contribute significantly to both the understanding of role of alkali during the reaction process and the mechanism study for the catalytic oxidation of cresols and non-hydroxyl aromatic hydrocarbons.
- Ma, Qiyi,Liang, Cheng,Chen, Kexian,Liu, Kejing,Mao, Jianyong,Chen, Zhirong,Li, Haoran
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- Isoquinolinium Dichromate and Chlorochromate as Efficient Catalysts for Oxidative Halogenation of Aromatic Compounds under Acid-Free Conditions
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Isoquinolinium dichromate and isoquinolinium chlorochromate were found as efficient catalysts to trigger oxidative bromination and iodination of aromatic hydrocarbons with KBr/KI and KHSO4 under acid-free conditions. Reaction times reduced highly significantly under sonication, followed by corresponding mono bromo derivatives in very good yield with high regioselectivity.
- Rao, A. Sambashiva,Rajanna,Reddy, K. Rajendar,Kulkarni, Subhash
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p. 832 - 837
(2016/02/12)
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- Aerobic oxidation of p-cresols to 4-hydroxy benzaldehydes catalyzed by cobaltous chloride/NHPI/salen-Cu(II) catalytic system
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Oxidation of 2-methoxy-p-cresol, p-cresol, 2-bromo-p-cresol to their corresponding 4-hydroxybenzaldehydes with atmospheric molecular oxygen as oxidant and a combination of cobaltous chloride and N-hydroxyphthalimide (NHPI) as catalyst in methanol has been investigated for the first time. The results indicated that the reaction progress was related to the substituents in the structures of the substrates: the electron-donating group methoxy favors the aerobic reaction but the electron-withdrawing group Br is detrimental to the reaction. The introduction of salen-Cu(II) complexes as the third component into the cobaltous chloride/NHPI catalytic system can considerably improve the aerobic oxidation of p-cresol and 2-brom-p-cresol to the corresponding 4-hydroxybenzaldes.
- Ma, Wenchan,Zhang, Yuecheng,Li, Xiujuan,Zhao, Jiquan
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p. 3855 - 3863
(2015/06/08)
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- A highly efficient approach to vanillin starting from 4-cresol
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A highly efficient approach to the famous flavor and fragrance compound vanillin has been developed starting from 4-cresol with the attention focused on improving the sustainability of all the reactions. The approach involves a three-step sequence of the quasi-quantitative selective clean oxybromination of 4-cresol, the high-yield selective aerobic oxidation of 2-bromo-4-cresol, and the quantitative methoxylation of 3-bromo-4-hydroxybenzaldehyde with the recovery of pure methanol. Herein, the pivotal oxidation and methoxylation reactions are logically investigated and developed into two concise methodologies. As a green alternative, the approach holds significant value for the sustainable manufacturing of vanillin. the Partner Organisations 2014.
- Jiang, Jian-An,Chen, Cheng,Guo, Ying,Liao, Dao-Hua,Pan, Xian-Dao,Ji, Ya-Fei
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p. 2807 - 2814
(2014/05/06)
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- Practical Cu(OAc)2/TEMPO-catalyzed selective aerobic alcohol oxidation under ambient conditions in aqueous acetonitrile
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We reported a ligand-and additive-free Cu(OAc)2/TEMPO catalyst system that enables efficient and selective aerobic oxidation of a broad range of primary and secondary benzylic alcohols, primary and secondary 1-heteroaryl alcohols, cinnamyl alcohols, and aliphatic alcohols to the corresponding aldehydes and ketones. This ambient temperature oxidation protocol is of practical features like aqueous acetonitrile as solvent, ambient air as the terminal oxidant, and low catalyst loading, presenting a potential value in terms of both economical and environmental considerations. Based on the experimental observations, a plausible reaction mechanism was proposed.
- Jiang, Jian-An,Du, Jia-Lei,Wang, Zhan-Guo,Zhang, Zhong-Nan,Xu, Xi,Zheng, Gan-Lin,Ji, Ya-Fei
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supporting information
p. 1677 - 1681
(2014/03/21)
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- Efficient Co(OAc)2-catalyzed aerobic oxidation of EWG-substituted 4-cresols to access 4-hydroxybenzaldehydes
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We reported an efficient ligand-free Co(OAc)2·4H 2O/NaOH/O2/ethylene glycol reaction system that enables selective aerobic oxidation of a wide range of substrates covering 2,6-di-EWG-, 2,3,6-tri-EWG-, 2-EWG-, and 2-EWG-6-EDG-substituted 4-cresols into the corresponding 4-hydroxybenzaldehydes. Based on the experimental investigations and well-defined p-benzoquinone methides, a plausible reaction mechanism was proposed. Considering the simplicity of the procedure and importance of the products, the methodology was expected to become a favorable and practical tool in related benzylic C(sp3)-H functionalization chemistry.
- Jiang, Jian-An,Du, Jia-Lei,Liao, Dao-Hua,Wang, Zhan-Guo,Ji, Ya-Fei
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supporting information
p. 1406 - 1411
(2014/03/21)
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- Cu(OAc)2-catalyzed remote benzylic C(sp3)-H oxyfunctionalization for C=O formation directed by the hindered para-hydroxyl group with ambient air as the terminal oxidant under ligand- and additive-free conditions
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A hindered para-hydroxyl group-directed remote benzylic C(sp3)-H oxyfunctionalization has been developed for the straightforward transformation of 2,6-disubstituted 4-cresols, 4-alkylphenols, 4-hydroxybenzyl alcohols and 4-hydroxybenzyl alkyl ethers into various aromatic carbonyl compounds. The ligand- and additive-free Cu(OAc)2-catalyzed atmospheric oxidation mediated by ethylene glycol unlocks a facile, atom-economical, and environmentally benign C=O formation for the functionalization of primary and secondary benzyl groups. Due to the pharmaceutical importance of 4-hydroxybenzaldehydes and 4-hydroxyphenones, the methodology is expected to be of significant value for both fundamental research and practical applications.
- Jiang, Jian-An,Chen, Cheng,Huang, Jian-Gang,Liu, Hong-Wei,Cao, Song,Ji, Ya-Fei
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supporting information
p. 1248 - 1254
(2014/03/21)
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- 2,2′-biphenols via protecting group-free thermal or microwave-accelerated suzuki-miyaura coupling in water
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User-friendly protocols for the protecting group-free synthesis of 2,2′-biphenols via Suzuki-Miyaura coupling of o-halophenols and o-boronophenol are presented. The reactions proceed in water in the presence of simple additives such as K2CO3, KOH, KF, or TBAF and with commercially available Pd/C as precatalyst. Expensive or laboriously synthesized ligands or other additives are not required. In the case of bromophenols, efficient rate acceleration and short reaction times were accomplished by microwave irradiation.
- Schmidt, Bernd,Riemer, Martin,Karras, Manfred
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p. 8680 - 8688
(2013/09/24)
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- Fluorescent analogs of the marine natural product psammaplin A: Synthesis and biological activity
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The symmetrical disulfide psammaplin A from the marine sponge Pseudoceratina sp. was synthesized and structurally altered by replacement of one of the α-(hydroxyimino)acyl units by a fluorescent 4-coumarinacetyl moiety. Thus, the first fluorescent analogs of psammaplin A were obtained. Structural variation also covered the substitution pattern of the phenyl ring. Cytotoxicity of psammaplin A against the mouse fibroblast cell line L-929 (IC50 0.42 μg mL-1) was about two-fold higher than that of the fluorescent hybrid compounds, whereas the disulfide containing two 4-coumarinacetyl moieties was inactive. Fluorescence microscopy revealed uptake of the 4-coumarinacetyl-α-(hydroxyimino)acyl hybrids into the cytoplasm leading to fluorescence in close proximity of the nuclear envelope, most likely in the Golgi apparatus. We did not observe strong fluorescence inside the nucleus, where most of the target histone deacetylases are located. We conclude that reduction of the disulfide probably takes place outside the nucleus. The psammaplin-derived thiol exhibited potent activity against histone deacetylase in the low nanomolar range, but diminished cytotoxicity. Antimicrobial activity of the new derivatives was also determined.
- Hentschel, Fabia,Sasse, Florenz,Lindel, Thomas
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experimental part
p. 7120 - 7133
(2012/09/22)
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- Inhibition of Acyl-CoA: Cholesterol acyltransferase (ACAT), overexpression of cholesterol transporter gene, and protection of amyloid β (Aβ) oligomers-induced neuronal cell death by tricyclic pyrone molecules
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A major effort in Alzheimers disease therapeutic development has targeted Aβ and downstream events. We have synthesized a small library of tricyclic pyrone compounds. Their protective action in MC65 cells and inhibition of ACAT along with the upregulation of cholesterol transporter gene were investigated. Five active compounds exhibited potencies in the nanomolar ranges. The multiple effects of the compounds on Aβ and cellular cholesterol pathways could be potential mechanisms underlying the protective effects in vivo.
- Pokhrel, Laxman,Maezawa, Izumi,Nguyen, Thi D. T.,Chang, Kyeong-Ok,Jin, Lee-Way,Hua, Duy H.
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p. 8969 - 8973
(2013/01/15)
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- Aromatic substitution in ball mills: Formation of aryl chlorides and bromides using potassium peroxomonosulfate and NaX
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Aryl chlorides and bromides are formed from arenes in a ball mill using KHSO5 and NaX (X = Cl, Br) as oxidant and halogen source, respectively. Investigation of the reaction parameters identified operating frequency, milling time, and the number of milling balls as the main influencing variables, as these determine the amount of energy provided to the reaction system. Assessment of liquid-assisted grinding conditions revealed, that the addition of solvents has no advantageous effect in this special case. Preferably activated arenes are halogenated, whereby bromination afforded higher product yields than chlorination. Most often reactions are regio- and chemoselective, since p-substitution was preferred and concurring side-chain oxidation of alkylated arenes by KHSO5 was not observed. The Royal Society of Chemistry.
- Schmidt, Robert,Stolle, Achim,Ondruschka, Bernd
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p. 1673 - 1679
(2013/02/22)
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- Regioselective and high-yielding bromination of phenols and anilins using N-bromosaccharin and amberlyst-15
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A regioselective and facile conversion method for bromination of anilines and phenols using N-bromosaccharine in the presence of a catalytic amount of Amberlyst-15 lead to enhancement of the reaction rate and yielded brominated products in good to excellent yields and short reaction times.
- Baharfar,Alinezhad,Azimi,Salehian
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experimental part
p. 863 - 865
(2012/04/23)
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- A concise synthetic approach to dihydrochalcone: First total syntheses of bipinnatone A and B
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The first total syntheses of bipinnatone A and B have been achieved starting from commercially available phloroglucinol, p-hydroxybenzaldehyde in ten steps. Key features of the syntheses include Aldol reaction, aryl-alkylation and InCl3-NaBH4 selective reduction.
- Zhao, Xiao Long,Li, Hui Zhi,Zhang, Xian Shu,Wang, Wen Jing,Da, Shi Jun,Li, Ying
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scheme or table
p. 1135 - 1138
(2012/01/06)
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- Design, synthesis and biological evaluation of novel 4-hydroxybenzene acrylic acid derivatives
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A series of 4-hydroxybenzene acrylic acid derivatives were designed and synthesized based on the ferulic acid of natural active ingredients. The tested compound 5a, 5f and 6a have significant anti-inflammatory activity with suppression rates of 45.29%, 44.75% and 24.11%, respectively, compared with that of indomethacin, and their cardiac toxicity was not observed. The structure-function relationship shows that the p-hydroxyl group on the α-position benzene ring, particularly if acetylated, contributes to the considerable anti-inflammatory activity; that the carboxyl group on the double bond, if esterified, also contributes to the anti-inflammatory activity; that the p-methylsulfonyl group on the other benzene ring, whose introduction is due to the COX-2 selectivity, also contributes to anti-inflammatory activity surprisingly.
- Mao, Jin-Long,Ran, Xiang-Kai,Tian, Jing-Zhen,Jiao, Bo,Zhou, Hong-Lei,Chen, Li,Wang, Zhen-Guo
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scheme or table
p. 1549 - 1553
(2011/04/22)
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- INHIBITORS OF ACETYL-COA CARBOXYLASE
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The present invention relates to compounds that act as acetyl-CoA carboxylase (ACC) inhibitors. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
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Page/Page column 37
(2010/11/17)
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- Total synthesis, antiprotozoal and cytotoxicity activities of rhuschalcone VI and analogs
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The total synthesis of a potent antiplasmodial natural bichalcone, rhuschalcone VI, is described starting from simple and available resorcinol and 4-hydroxybenzaldehyde. Key steps include the solvent-free Aldol syntheses of chalcones, and the successful application of the Suzuki-Miyaura coupling reaction in the synthesis of bichalcones. The present work constitutes a general method for the rapid syntheses of a number of bichalcones related to rhuschalcone VI. Some of the bichalcones showed moderate antiprotozoal activities against Bodo caudatus, a preliminary screening system for antitrypanosomal activities, most of them with little or no cytotoxicity.
- Mihigo, Shetonde O.,Mammo, Wendimagegn,Bezabih, Merhatibeb,Andrae-Marobela, Kerstin,Abegaz, Berhanu M.
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scheme or table
p. 2464 - 2473
(2010/07/02)
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- Synthesis and elucidation of deuterated vanillylamine hydrochloride and capsaicin
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Capsaicin is the major pungent component of hot peppers, which belong to the plant genus Capsicum. Although the biosynthesis of capsaicin is known to involve the condensation of vanillylamine and 8-methylnonenoic acid by capsaicin synthase, the mechanism of biosynthesis is still not fully understood. In this study, deuterium labelled versions of capsaicin and the precursor vanillylamine were synthesized in order to investigate the biosynthesis of capsaicin in hot peppers. Copyright
- Kim, Sang Wook,Park, Jeong Hoon,Jung, Soon Jae,Choi, Tae Bum,Hur, Min Goo,Yang, Seung Dae,Yu, Kook Hyun
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experimental part
p. 563 - 565
(2010/07/02)
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- Dual aromatase-steroid sulfatase inhibitors
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By introducting the steroid sulfatase inhibitory pharmacophore into aromatase inhibitor 1 (YM511), two series of single agent dual aromatase-sulfatase inhibitors (DASIs) were generated. The best DASIs in'vitro (JEG-3 cells) are 5, (IC50(aromatase) = 0.82 nM; IC 50(sulfatase) = 39 nM), and 14, (IC50(aromatase) = 0.77 nM; IC50(sulfatase) = 590 nM). X-ray crystallography of 5, and docking studies of selected compounds into an aromatase homology model and the steroid sulfatase crystal structure are presented. Both 5 and 14 inhibit aromatase and sulfatase in PMSG pretreated adult female Wistar rats potently 3 h after a single oral 10 mg/kg dose. Almost complete dual inhibition is observed for 5 but the levels were reduced to 85% (aromatase) and 72% (sulfatase) after 24 h. DASI 5 did not inhibit aldosterone synthesis. The development of a potent and selective DASI should allow the therapeutic potential of dual aromatase-sulfatase inhibition in hormone-dependent breast cancer to be assessed.
- Woo, L. W. Lawrence,Bubert, Christian,Sutcliffe, Oliver-B.,Smith, Andrew,Chander, Surinder K.,Mahon, Mary F.,Purohit, Atul,Reed, Michael J.,Potter, Barry V. L.
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p. 3540 - 3560
(2008/02/09)
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- INDAZOLE DERIVATIVES
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The present invention provides a compound represented by Formula (I): [whetein R1 represents CONR1aR1b (wherein R1a and R1b may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted ararkyl or a substituted or unsubstituted heterocyclic group, or R1a and R1b are combined together with the adjacent nitrogen atom thereto to form a substituted or unsubstituted heterocyclic group) or the like, R2 represents a hydrogen atom, CONR2aR2b (wherein R2a and R2b may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted ararkyl or a substituted or unsubstituted heterocyclic group, or R2a and R2b are combined together with the adjacent nitrogen atom thereto to form a substituted or unsubstituted heterocyclic group), NR2cR2d (wherein R2c and R2d may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkanoyl, substituted or unsubstituted aroyl, substituted or unsubstituted heteroaroyl, substituted or unsubstituted ararkyl, substituted or unsubstituted lower alkylsulfonyl or substituted or unsubstituted lower arylsulfonyl) or the like].
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Page/Page column 31
(2008/06/13)
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- PROTEIN KINASE INHIBITOR
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The present invention provides a protein kinase inhibitor (excluding c-Jun N-terminal kinase inhibitor) which comprises, as an active ingredient, an indazole derivative represented by Formula (I) (wherein R1 represents substituted or unsubstituted aryl or a substituted or unsubstituted heterocyclic group) or a pharmaceutically acceptable salt thereof.
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Page/Page column 32
(2010/11/08)
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- Tetrameric DABCO-bromine: An efficient and versatile reagent for bromination of various organic compounds
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Tetrameric DABCO-bromine is a powerful brominating agent but shows reasonable selectivity with certain substrates. The selective bromination for activated aromatic compounds and alkenes is reported. Synthesis of α-bromo ketones and nitriles has also been achieved by using this reagent and the results are also reported. All products reported were obtained in good to excellent yields.
- Heravi, Majid M.,Derikvand, Fatemeh,Ghassemzadeh, Mitra
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p. 125 - 128
(2007/10/03)
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- ALYKYLENE DERIVATIVE HAVING EDG RECEPTOR ANTAGONISM
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PROBLEM TO BE SOLVED: To provide novel compounds having EDG (endothelial differentiation gene) receptor antagonism which are useful as active components of drugs for preventing and/or treating inflammatory diseases or the like. SOLUTION: The compounds are represented by formula (I) (wherein R1 is hydrogen or an alkyl group; R2 is hydrogen present at any substitutable position on ring C or a substituent such as a hydroxy group, a carboxy group, and a nitro group; R3 is hydrogen present at any substitutable position on ring D or a substitutent such as a hydroxy group and an aralkyloxy group; X is an alkylamino group, an amino group or the like; Y is a carboxy group, a sulfo group or a phosphono group; Z is oxygen, sulfur or the like; a ring represented by A is a 5- or 6-membered saturated or unsaturated hydrocarbon ring; and a ring represented by B is a 4- or 7-membered saturated or unsaturated hydrocarbon ring containing one -C=C- as a partial structure shown in the above formula) and include their salts and their esters.
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Page/Page column 129
(2010/02/12)
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- Regioselective and high-yielding bromination of aromatic compounds using hexamethylenetetramine-bromine
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A regioselective and highly efficient method for bromination of aromatic compounds in the presence of a stoichiometric amount of hexamethylenetetramine- bromine (HMTAB) as an efficient reagent in dichloromethane is reported. The selectivity depends on the temperature and nature of the substituent on the substrate. The reactivity of this reagent was increased by supporting it to silica gel for bromination of less activated compounds.
- Heravi, Majid M.,Abdolhosseini, Nafiseh,Oskooie, Hossein A.
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p. 8959 - 8963
(2007/10/03)
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- Galanthamine analogs: 6H-benzofuro[3a,3,2,-e,f][1]benzazepine and 6H-benzofuro[3a,3,2-e,f][3]benzazepine
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The known cholinesterase inhibitory capability of the Amarylidaceae alkaloid galanthamine prompted preparation of analogs in which the position of the nitrogen within the azepine ring is altered. The analogs 6H-benzofuro[3a,3,2-e,f][1]benzazepine and 6H-benzofuro[3a,3,2-e,f][3] benzazepine were prepared in 19 and 2.5%, respectively, following Kametani and Shimizu approaches, respectively. The aniline derivative 6H-benzofuro[3a,3,2-e, f][1]benzazepine failed to undergo most of the reactions typical for galanthamine. Thus, it neither oxidized to the analogous narwedine, nor epimerized to the analogous epigalanthamine, nor reduced to the lycoramine analog, under the conditions used for galanthamine.
- Lewin, Anita H.,Szewczyk, Jerzy,Wilson, Joseph W.,Carroll, F. Ivy
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p. 7144 - 7152
(2007/10/03)
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- Syntheses and radical scavenging activities of resveratrol derivatives
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Nine new resveratrol derivatives, having bromo, iodo, and fluoroethyl groups, were designed and synthesized. All compounds having free phenol groups showed good free radical scavenging activity. Among them, 2-bromoresveratrol 19 has a similar free radical scavenging activity to (+)-catechin.
- Lee, Hyun Jung,Seo, Jai Woong,Lee, Bong Ho,Chung, Kyoo-Hyun,Chi, Dae Yoon
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p. 463 - 466
(2007/10/03)
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- Substituted phenylalkanoic acid derivatives and use thereof
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A compound represented by the formula (I) or a salt thereof: wherein n represents an integer of 1 to 3, R represents an alkyl group having 3 to 8 carbon atoms, a group represented by the following formula: R1(CH2)k— (wherein k represents 0 or an integer of 1 to 3; R1 represents a saturated cyclic alkyl group having 3 to 7 carbon atoms or a saturated condensed cyclic alkyl group having 6 to 8 carbon atoms, and the group R1 may be substituted with a lower alkyl group having 1 to 4 carbon atoms) and the like, and Ar represents a condensed bicyclic group such as naphthalen-1-yl group, which has suppressing action on prostaglandin and leukotriene production and is useful for prophylactic and/or therapeutic treatment of various inflammatory diseases and the like caused by these lipid mediators.
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- Compound
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There is provided a compound of Formula I 1 wherein each T is independently selected from H, hydrocarbyl, —F—R, and a bond with one of D, E, P or Q, or together with one of P and Q forms a ring; Z is a suitable atom the valency of which is m; D, E and F are each independently of each other an optional linker group, wherein when Z is nitrogen E is other than CH2 and C═O; P, Q and R are independently of each other a ring system; and at least Q comprises a sulphamate group.
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Page/Page column 39
(2008/06/13)
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- Flavonoid derivatives as organometallic bioprobes
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The synthesis of organoiron derivatives of biologically active flavonoids is described. Lithium enolates of functionalised protected acetophenones and metallated derivatives of substituted aromatic rings have been employed as nucleophiles in combination with tricarbonyl(η5-cyclohexadienyl)iron electrophiles. Products have been converted into flavonoid and chalcone derivatives. Enolates generated from protected flavanones have also been used in nucleophile addition reactions, and a one-pot in situ protection, nucleophile addition, deprotection sequence is reported.
- Anson, Christopher E.,Creaser, Colin S.,Malkov, Andrej V.,Mojovic, Ljubica,Stephenson, G. Richard
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p. 101 - 122
(2007/10/03)
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- First dual aromatase-steroid sulfatase inhibitors
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Aromatase inhibitors in clinical use block the biosynthesis of estrogens. Hydrolysis of estrone 3-sulfate by steroid sulfatase is an important additional source of tumor estrogen, and blockade of both enzymes should provide a more effective endocrine therapy. Sulfamoylated derivatives of the aromatase inhibitor YM511 inhibited sulfatase and aromatase in JEG-3 cells with respective IC50 values of 20-227 and 0.82-100 nM (cf. letrozole, 0.89 nM). One dual inhibitor was potent against both enzymes in vivo, validating the concept.
- Woo, L.W. Lawrence,Sutcliffe, Oliver B.,Bubert, Christian,Grasso, Anna,Chander, Surinder K.,Purohit, Atul,Reed, Michael J.,Potter, Barry V. L.
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p. 3193 - 3196
(2007/10/03)
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- Bicyclic aromatic compounds and pharmaceutical/cosmetic compositions comprised thereof
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Novel pharmaceutically/cosmetically-active bicyclic aromatic compounds have the structural formula (I): in which Ar1 is a radical having one of the structural formulae (a)-(c): Ar2 is a radical having one of the following formulae (d)-(h): and X is a radical having one of the following formulae (i)-(l): and are useful for the treatment of a wide variety of disease states, whether human or veterinary, for example dermatological, rheumatic, respiratory, cardiovascular and ophthalmological disorders, as well as for the treatment of mammalian skin and hair conditions/disorders.
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Page/Page column 13
(2010/01/31)
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- Compounds, compositions and methods for treating or preventing pneumovirus infection and associated diseases
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Compounds, compositions and methods are provided for the prophylaxis and treatment of infections caused by viruses of the Pneumovirinae subfamily of Paramyxoviridae and diseases associated with such infections.
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- First enantioselective total synthesis of (-)-tejedine
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(Matrix presented) The first enantioselective total synthesis of (-)-tejedine (1) is reported. Tejedine is a seco-bisbenzyltetrahydroisoquinoline isolated in 1998 as a minor component from Berberis vulgaris. The synthesis was achieved using a strategy employing four key steps, including a chiral auxiliary-assisted diastereoselective Bischler-Napieralski cyclization.
- Wang, You-Chu,Georghiou, Paris E.
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p. 2675 - 2678
(2007/10/03)
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- 4,4-Dibromo-3-methylpyrazol-5-one: New applications for selective monobromination of phenols and oxidation of sulfides to sulfoxides
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Dibromopyrazolone 1, a stable, crystalline solid effects para selective monobromination of phenols and aniline substrates under mild conditions. Selective oxidation of sulfides to sulfoxides can also be accomplished by using 1 in high yields.
- Mashraqui, Sabir H.,Mudaliar, Chandrashekar D.,Hariharasubrahmanian, Harini
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p. 4865 - 4868
(2007/10/03)
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- A concise and efficient synthesis of protected actinoidic acid, the degradation product of vancomycin
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Protected actinoidic acid 2, one of the degradation products of vancomycin, has been efficiently synthesized by a convergent route which is amenable to large scale application as well as to asymmetric synthesis.
- Zhu, Jieping,Beugelmans, Rene,Bigot, Antony,Singh, Girij Pal,Bois-Choussy, Michele
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p. 7401 - 7404
(2007/10/02)
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- SELECTIVE MONOBROMINATION OF PHENOLS
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A method is proposed for the selective monobromination of the hydroxy derivatives of benzene with bis(dimethylacetamide)hydrogen tribromide in aprotic media as brominating agent.
- Mikhailov, V. A.,Savelova, V. A.,Rodygin, M. Yu.
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p. 1868 - 1870
(2007/10/02)
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- Process for production of aromatic aldehydes
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Aromatic aldehydes are produced by oxidation with oxygen of a para-cresol derivative in a solvent, in the presence of a base and a catalytic amount of a cobalt compound. The catalyst is a chelated complex of cobalt with a rigid structure that is slightly oxidizable selected from the group consisting of bis-(4-methylpyridine isoindolinato)cobalt(II) acetate, phthalocyaninatocobalt(II), and sulfophthalocyaninanatocobalt(II). The process is particularly suited to the production of p-hydroxy benzaldehydes.
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- On the Synthesis of Tiliacora Alkaloids, I: Synthesis of The Ansymmetrical Dibenzo-1,4-dioxin-Derivative
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The N-protected phenylethylamines 2 and 3, respectively, were synthesized in six steps, starting from 2a and 3a.The mixed double Ullmann reaction of 2 with 3 leads to the asymmetrical dibenzo-1,4-dioxin derivative K.On account of the selectively removable protective groups for the amino functions, K is a proper intermediate for the constitution-selective synthesis of the tiliacora alkaloids 1a - 1d.
- Pachaly, Peter,Schaefer, Michael
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p. 477 - 482
(2007/10/02)
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