- Palladium-Catalyzed Dearomative syn-1,4-Carboamination
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A dearomative 1,4-carboamination of arenes has been achieved using arenophile cycloaddition and subsequent palladium-catalyzed substitution with nonstabilized lithium enolates. This protocol delivers products with exclusive syn-1,4-selectivity and can be also conducted in an asymmetric fashion. The method allows rapid dearomative difunctionalization of simple aromatic compounds into functional small molecules amenable to further diversification.
- Okumura, Mikiko,Shved, Alexander S.,Sarlah, David
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- An Improved Synthesis of Balsaminone A
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A short and efficient synthesis of balsaminone A, a dinaphthofuran-1,4-dione, is described. The eight-step synthesis features two alternate pathways including a base-induced coupling reaction of 4-methoxy-1-naphthol and 2,3-dichloro-1,4-naphthoquinone, as well as a light-mediated cyclization of 1,1'-binaphthoquinone to afford the dinaphthofurandione core. Subsequent ortho formylation yielded a known precursor to balsaminone A, affording the natural product in 20-27% yield. This represents a moderate increase from the previous synthesis of 7.4% yield.
- Daley, Sharna-Kay A.,Downer-Riley, Nadale K.
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- Synthesis of new vitamin K analogues as steroid and xenobiotic receptor (SXR) agonists: Insights into the biological role of the side chain part of vitamin K
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Vitamin K2 has been demonstrated to induce gene expression related to bone formation through a nuclear steroid and xenobiotic receptor (SXR). We synthesized new vitamin K analogues with the same isoprene side chains symmetrically introduced at the 2 and 3 positions of 1,4-naphthoquinone and evaluated the transcriptional activity of the target gene. The transcriptional activity was related to the length of the side chain which allowed optimal interaction with ligand-binding domain of SXR.
- Suhara, Yoshitomo,Watanabe, Masato,Motoyoshi, Sayaka,Nakagawa, Kimie,Wada, Akimori,Takeda, Kazuyoshi,Takahashi, Kazuhiko,Tokiwa, Hiroaki,Okano, Toshio
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- Conformational Planarization versus Singlet Fission: Distinct Excited-State Dynamics of Cyclooctatetraene-Fused Acene Dimers
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A set of flapping acene dimers fused with an 8π cyclooctatetraene (COT) ring showed distinct excited-state dynamics in solution. While the anthracene dimer showed a fast V-shaped-to-planar conformational change within 10 ps in the lowest excited singlet state, reminding us of extended Baird aromaticity, the tetracene dimer and the pentacene dimer underwent intramolecular singlet fission (SF) in different manners: A fast and reversible SF with a characteristic delayed fluorescence (FL), and a fast and quantitative SF, respectively. Conformational flexibility of the fused COT linkage plays an important role in these ultrafast dynamics, demonstrating the utility of the flapping molecular series as a versatile platform for designing photofunctional systems.
- Yamakado, Takuya,Takahashi, Shota,Watanabe, Kazuya,Matsumoto, Yoshiyasu,Osuka, Atsuhiro,Saito, Shohei
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- Stereoselective [4+2] cycloaddition of singlet oxygen to naphthalenes controlled by carbohydrates
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Stereoselective reactions of singlet oxygen are of current interest. Since enantioselective photooxygenations have not been realized efficiently, auxiliary control is an attractive alternative. However, the obtained peroxides are often too labile for isolation or further transformations into enantiomerically pure products. Herein, we describe the oxidation of naphthalenes by singlet oxygen, where the face selectivity is controlled by carbohydrates for the first time. The synthesis of the precursors is easily achieved starting from naphthoquinone and a protected glucose derivative in only two steps. Photooxygenations proceed smoothly at low temperature, and we detected the corresponding endoperoxides as sole products by NMR. They are labile and can thermally react back to the parent naphthalenes and singlet oxygen. However, we could isolate and characterize two enantiomerically pure peroxides, which are sufficiently stable at room temperature. An interesting influence of substituents on the stereoselectivities of the photooxygenations has been found, ranging from 51:49 to up to 91:9 dr (diastereomeric ratio). We explain this by a hindered rotation of the carbohydrate substituents, substantiated by a combination of NOESY measurements and theoretical calculations. Finally, we could transfer the chiral information from a pure endoperoxide to an epoxide, which was isolated after cleavage of the sugar chiral auxiliary in enantiomerically pure form.
- Bauch, Marcel,Fudickar, Werner,Linker, Torsten
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- Rational designed highly sensitive NQO1-activated near-infrared fluorescent probe combined with NQO1 substrates in vivo: An innovative strategy for NQO1-overexpressing cancer theranostics
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Since NQO1 is overexpressed in many cancer cells, it can be used as a biomarker for cancer diagnosis and targeted therapy. NQO1 substrates show potent anticancer activity through the redox cycle mediated by NQO1, while the NQO1 probes can monitor NQO1 levels in cancers. High sensitivity of probes is needed for diagnostic imaging in clinic. In this study, based on the analysis of NQO1 catalytic pocket, the naphthoquinone trigger group 13 rationally designed by expanding the aromatic plane of the benzoquinone trigger group 10 shows significantly increased sensitivity to NQO1. The sensitivity of the naphthoquinone trigger group-based probe A was eight times higher than that of benzoquinone trigger group-based probe B in vivo. Probe A was selectively and efficiently sensitive to NQO1 with good safety profile and plasma stability, enabling its combination with NQO1 substrates in vivo for NQO1-overexpressing cancer theranostics for the first time.
- Gong, Qijie,Yang, Fulai,Hu, Jiabao,Li, Tian,Wang, Pengfei,Li, Xiang,Zhang, Xiaojin
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- Single-atom cobalt-fused biomolecule-derived nitrogen-doped carbon nanosheets for selective oxidation reactions
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Non-noble metal single-atom catalysts hold great promise in selective oxidation reactions, although the progress is still unsatisfactory because of the synthesis challenge and the lack of mechanistic interpretations. Herein, we develop a biomolecule-based strategy to synthesize isolated Co single atom site catalysts by one-step pyrolysis of guanosine and Co precursors. Due to the abundant hydrogen bonding and π-π interaction of guanosine, the as-synthesized Co-N-C catalysts present a hierarchical porous two-dimensional (2D) nanostructure with an ultrahigh specific surface area, large pore volume, and high density of cobalt single atoms. Aberration-corrected electron microscopy and X-ray photoelectron spectroscopy reveal that Co species are present as isolated single sites and stabilized by nitrogen-doped carbon nanosheets. These characteristics make Co-GS-900 suitable as an efficient catalyst for selective oxidation of aromatic alkanes. For oxidation of ethylbenzene, Co-GS-900 exhibits a superior performancefwith 91% conversion and 98% selectivity of acetophenone.
- Huang, Haitao,Wei, Qiao-Hua,Xia, Miao,Xie, Zailai,Zhang, Xuefei
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p. 14276 - 14283
(2021/07/13)
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- Determining Proton-Coupled Standard Potentials and X-H Bond Dissociation Free Energies in Nonaqueous Solvents Using Open-Circuit Potential Measurements
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Proton-coupled electron transfer (PCET) reactions are increasingly being studied in nonaqueous conditions, where the thermochemistry of PCET substrates is largely unknown. Herein, we report a method to obtain electrochemical standard potentials and calculate the corresponding bond dissociation free energies (BDFEs) of stable PCET reagents in nonaqueous solvents, using open-circuit potential (OCP) measurements. With this method, we measure PCET thermochemistry in acetonitrile and tetrahydrofuran for substrates with O-H and N-H bonds that undergo 1e-/1H+ and 2e-/2H+ redox processes. We also report corrected thermochemical values for the 1/2H2(g)/H?1M and H+/H? (CG) couples in several organic solvents. For 2e-/2H+ couples, OCP measurements provide the multielectron/multiproton standard potential and the average of the two X-H BDFEs. In contrast to traditional approaches for calculating BDFEs from electrochemical measurements, the OCP method directly measures the overall PCET reaction thermodynamics and avoids the need for a pKa scale in the solvent of interest. Consequently, the OCP approach yields more accurate thermochemical values and should be general to any solvent mixture compatible with electrochemical measurements. The longer time scale of OCP measurements enables accurate thermochemical measurements for redox couples with irreversible or distorted electrochemical responses by cyclic voltammetry, provided the PCET reaction is chemically reversible. Recommendations for successful OCP measurements and limitations of the approach are discussed, including the current inability to measure processes involving C-H bonds. As a straightforward and robust technique to determine nonaqueous PCET thermochemistry, these OCP measurements will be broadly valuable, with applications ranging from fundamental reactivity studies to device development.
- Agarwal, Rishi G.,Mayer, James M.,Wise, Catherine F.
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supporting information
p. 10681 - 10691
(2020/07/06)
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- Mechanistic and crystallographic studies of azoreductase azoa from bacillus wakoensis a01
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The azoreductase AzoA from the alkali-tolerant Bacillus wakoensis A01 has been studied to reveal its structural and mechanistic details. For this, a recombinant expression system was developed which yields impressive amounts of fully active enzyme. The purified holo enzyme is remarkably solvent-tolerant and thermostable with an apparent melting temperature of 71 °C. The dimeric enzyme contains FMN as a prosthetic group and is strictly NADH dependent. While AzoA shows a negligible ability to use molecular oxygen as an electron acceptor, it is efficient in reducing various azo dyes and quinones. The kinetic and catalytic mechanism has been studied in detail using steady state kinetic analyses and stopped-flow studies. The data show that AzoA performs quinone and azo dye reductions via a two-electron transfer. Moreover, quinones were shown to be much better substrates (kcat values of 100-400 s-1 for several naphtoquinones) when compared with azo dyes. This suggests that the physiological role of AzoA and sequence-related microbial reductases is linked to quinone reductions and that they can better be annotated as quinone reductases. The structure of AzoA has been determined in complex with FMN at 1.8 ? resolution. AzoA displays unique features in the active site providing clues for explaining its catalytic and thermostability features. An uncommon loop, when compared with sequence-related reductases, forms an active site lid with Trp60 acting as an anchor. Several Trp60 mutants have been analyzed disclosing an important role of this residue in the stability of AzoA, while they retained activity. Structural details are discussed in relation to other azo and quinone reductases. This study provides new insights into the molecular functioning of AzoA and sequence-related reductases.
- Fraaije, Marco W.,Lon?ar, Nikola,Romero, Elvira,Savino, Simone
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p. 504 - 512
(2020/03/11)
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- Erratum: Continuous-Flow Photochemical Transformations of 1,4-Naphthoquinones and Phthalimides in a Concentrating Solar Trough Reactor (Aust. J. Chem. (2020) 73(12):1149-1157)
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The authors wish to advise of errors in the above paper. In Table 3, footnote C should read 'Crude product contains 4-methylanisole or p-tolyl acetate.' In the left column of text on the same page as Table 3, the second last sentence should read 'When the para-substituted arylacetates 9b and 9c were employed, 4-methylanisole and p-tolyl acetate were detected by 1H NMR analysis of the crude reaction mixtures but no attempts were made to isolate these simple decarboxylation products.'
- Yaseen, Madyan A.,Mumtaz, Saira,Hunter, Richard L.,Wall, Daniel,Robertson, Mark J.,Oelgem?ller, Michael
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p. 1149 - 1157
(2020/07/30)
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- Exponential Molecular Amplification by H2O2-Mediated Autocatalytic Deprotection of Boronic Ester Probes to Redox Cyclers
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Herein, a new molecular autocatalytic reaction scheme based on a H2O2-mediated deprotection of a boronate ester probe into a redox cycling compound is described, generating an exponential signal gain in the presence of O2 and a reducing agent or enzyme. For such a purpose, new chemosensing probes built around a naphthoquinone/naphthohydroquinone redox-active core, masked by a self-immolative boronic ester protecting group, were designed. With these probes, typical autocatalytic kinetic traces with characteristic lags and exponential phases were obtained by using either UV/Visible or fluorescence optical detection, or by using electrochemical monitoring. Detection of concentrations as low as 0.5 μm H2O2 and 0.5 nm of a naphthoquinone derivative were achieved in a relatively short time (2O2 or redox cycling compounds, or for use as a new building block in the development of more complex chemical reaction networks.
- Pallu, Justine,Rabin, Charlie,Creste, Geordie,Branca, Mathieu,Mavré, Fran?ois,Limoges, Beno?t
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p. 7534 - 7546
(2019/04/13)
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- Direct Synthesis of Hydroquinones from Quinones through Sequential and Continuous-Flow Hydrogenation-Derivatization Using Heterogeneous Au–Pt Nanoparticles as Catalysts
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Pt–Au bimetallic nanoparticle catalysts immobilized on dimethyl polysilane (Pt–Au/(DMPSi-Al2O3)) have been developed for selective hydrogenation of quinones to hydroquinones. High reactivity, selectivity, and robustness of the catalysts were confirmed under continuous-flow conditions. Various direct derivatizations of quinones, such as methylation, acetylation, trifluoromethanesulfonylation, methacrylation, and benzoylation were successfully performed under sequential and continuous-flow conditions to afford the desired products in good to excellent yields. Especially, air-sensitive hydroquinones, such as anthrahydroquinones and naphthohydroquinones, could be successfully generated and derivatized under closed sequential and continuous-flow conditions without decomposition.
- Miyamura, Hiroyuki,Tobita, Fumiya,Suzuki, Aya,Kobayashi, Shū
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supporting information
p. 9220 - 9224
(2019/06/13)
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- Efficient Syntheses of Diverse, Medicinally Relevant Targets Planned by Computer and Executed in the Laboratory
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The Chematica program was used to autonomously design synthetic pathways to eight structurally diverse targets, including seven commercially valuable bioactive substances and one natural product. All of these computer-planned routes were successfully executed in the laboratory and offer significant yield improvements and cost savings over previous approaches, provide alternatives to patented routes, or produce targets that were not synthesized previously. Although computers have demonstrated the ability to challenge humans in various games of strategy, their use in the automated planning of organic syntheses remains unprecedented. As a result of the impact that such a tool could have on the synthetic community, the past half century has seen numerous attempts to create in silico chemical intelligence. However, there has not been a successful demonstration of a synthetic route designed by machine and then executed in the laboratory. Here, we describe an experiment where the software program Chematica designed syntheses leading to eight commercially valuable and/or medicinally relevant targets; in each case tested, Chematica significantly improved on previous approaches or identified efficient routes to targets for which previous synthetic attempts had failed. These results indicate that now and in the future, chemists can finally benefit from having an “in silico colleague” that constantly learns, never forgets, and will never retire. Multistep synthetic routes to eight structurally diverse and medicinally relevant targets were planned autonomously by the Chematica computer program, which combines expert chemical knowledge with network-search and artificial-intelligence algorithms. All of the proposed syntheses were successfully executed in the laboratory and offer substantial yield improvements and cost savings over previous approaches or provide the first documented route to a given target. These results provide the long-awaited validation of a computer program in practically relevant synthetic design.
- Klucznik, Tomasz,Mikulak-Klucznik, Barbara,McCormack, Michael P.,Lima, Heather,Szymku?, Sara,Bhowmick, Manishabrata,Molga, Karol,Zhou, Yubai,Rickershauser, Lindsey,Gajewska, Ewa P.,Toutchkine, Alexei,Dittwald, Piotr,Startek, Micha? P.,Kirkovits, Gregory J.,Roszak, Rafa?,Adamski, Ariel,Sieredzińska, Bianka,Mrksich, Milan,Trice, Sarah L.J.,Grzybowski, Bartosz A.
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supporting information
p. 522 - 532
(2018/03/21)
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- Generation and Confinement of Long-Lived N-Oxyl Radical and Its Photocatalysis
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Generation of controllable carbon radical under the assistance of N-oxyl radical is an efficient method for the activation of C-H bonds in hydrocarbons. We herein report that irradiation of α-Fe2O3 and N-hydroxyphthalimide (NHPI) under 455 nm light generates phthalimide-N-oxyl radical (PINO), which after being formed by oxidation with holes, is confined on α-Fe2O3 surface. The half-life time of the confined radical reaches 22 s as measured by in situ electron paramagnetic resonance (EPR) after the light being turned off. This allows the long-lived N-oxyl radical to abstract the H from C-H bond to form a carbon radical that reacts with molecular oxygen to form R3C-OO· species, decomposition of which leads to oxygenated products.
- Zhang, Chaofeng,Huang, Zhipeng,Lu, Jianmin,Luo, Nengchao,Wang, Feng
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p. 2032 - 2035
(2018/02/19)
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- Catalytic Electrophilic Alkylation of p-Quinones through a Redox Chain Reaction
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Allylation and benzylation of p-quinones was achieved through an unusual redox chain reaction. Mechanistic studies suggest that the existence of trace hydroquinone initiates a redox chain reaction that consists of a Lewis acid catalyzed Friedel–Crafts alkylation and a subsequent redox equilibrium that regenerates hydroquinone. The electrophiles could be various allylic and benzylic esters. The addition of Hantzsch ester as an initiator improves the efficiency of the reaction.
- Xu, Xiao-Long,Li, Zhi
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supporting information
p. 8196 - 8200
(2017/06/30)
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- Synthesis and radical scavenging activity of substituted Benzo [H] chromanols
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Benzo[h]chromanols, which possess a tocopherol moiety, have been reported to exhibit potent antioxidant activity. Several benzo[h]chromanols with various substituents (nitro, chloro, bromo, methyl, or amino groups at the position ortho to the phenolic OH group) were synthesized, and the second-order rate constants (k) of their reaction with the galvinoxyl radical were determined. The introduction of electron-withdrawing bromo, chloro and nitro groups decreased the activity, and the activity correlated well with the substituent effect. ortho-Aminobenzo[h]chromanol showed the highest radical scavenging activity among the compounds synthesized.
- Okayama, Yuta,Harada, Masanori,Morita, Mine,Mochizuki, Masataka,Inami, Keiko
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p. 865 - 878
(2017/06/13)
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- Diels-Alder trapping of in situ generated dienes from 3,4-dihydro-2H-pyran with p-quinone catalysed by p-toluenesulfonic acid
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This comprehensive study portrays that p-toluenesulfonic acid is a more efficient catalyst for the reaction between p-quinones and 3,4-dihydro-2H-pyran, than the Lewis acids. The products were accomplished by the Diels-Alder cycloaddition reaction and their mechanistic pathways have been formulated. The impact of C2 and C2,5 substituents of the p-quinones on the cycloaddition reaction has been explored. Remarkably, it is the first report to explore this kind of in situ generated diene for the Diels-Alder cycloaddition reaction.
- Mohan Raj, Radhakrishnan,Balasubramanian, Kalpattu K.,Easwaramoorthy, Deivanayagam
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p. 1115 - 1121
(2017/02/10)
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- Homolytic Cleavage of a B-B Bond by the Cooperative Catalysis of Two Lewis Bases: Computational Design and Experimental Verification
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Density functional theory (DFT) investigations revealed that 4-cyanopyridine was capable of homolytically cleaving the B-B σ bond of diborane via the cooperative coordination to the two boron atoms of the diborane to generate pyridine boryl radicals. Our experimental verification provides supportive evidence for this new B-B activation mode. With this novel activation strategy, we have experimentally realized the catalytic reduction of azo-compounds to hydrazine derivatives, deoxygenation of sulfoxides to sulfides, and reduction of quinones with B2(pin)2 at mild conditions. Breaking good: The diborane B-B bond can be homolytically cleaved via the cooperative catalysis of two 4-cyanopyridine molecules. Using this combination of a diborane (B2(pin)2) and 4-cyanopyridine also allows the catalytic reduction of the N=N double bond of azo-compounds to hydrazine derivatives, deoxygenation of sulfoxides to sulfides, and reduction of quinones under mild conditions.
- Wang, Guoqiang,Zhang, Honglin,Zhao, Jiyang,Li, Wei,Cao, Jia,Zhu, Chengjian,Li, Shuhua
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p. 5985 - 5989
(2016/05/19)
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- Naphthoquinone derivative containing adamantyl and preparation method and application of derivative
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The invention provides a naphthoquinone derivative containing adamantyl and a preparation method and application of the derivative, and particularly provides a naphthoquinone derivative which is as shown in a following formula (I) and contains adamantyl, wherein definitions of all groups are described in the description. The compound has Sortase A enzyme inhibitory activity and cytotoxic activity and can be used for treating diseases related to Sortase A enzyme and various malignant tumors. Please see the formula (I) in the description.
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Paragraph 0199-0201
(2017/01/05)
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- Benzoquinone and naphthoquinone based redox-active labels for electrochemical detection of modified oligonucleotides on Au electrodes
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The reaction of 1,4-benzoquinone and 1,4-naphthoquinone with β-thiopropionic acid yielded 3-[(3,6-dioxocyclohexa-1,4-diene-1-yl)thio]propionic and 3-[(1,4-dioxo-1,4-dihydronaphthalene-2-yl)thio]propionic acids, respectively. These compounds were used to modify oligonucleotides to allow their electrochemical detection on the surface of Au electrodes using cyclic voltammetry. Electrochemical reduction of the corresponding amides, modeling the bonding of the redox-active labels with molecules that are not electrochemically active, was also studied.
- Shundrin, Leonid A.,Irtegova, Irina G.,Vasilieva, Nadezhda V.,Khalfina, Irina A.
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supporting information
p. 392 - 395
(2016/01/12)
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- Polypeptides having peroxygenase activity and polynucleotides encoding same
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The present invention relates to isolated polypeptides having peroxygenase activity, and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.
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Page/Page column 37
(2016/08/07)
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- Toward Naphthocyclinones: Doubly Connected Octaketide Dimers with a Bicyclo[3.2.1]octadienone Core by Thiolate-Mediated Cyclization
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A viable method is reported for the synthesis of the bicyclo[3.2.1]octadienone scaffold in naturally occurring octaketide dimers. The procedure employs a reductive cyclization reaction mediated by an unusual ethanedithiol monosodium salt. Doubling up: A viable method for the construction of bicyclo[3.2.1]octadienone scaffolds has been developed, involving the reductive cyclization of dimeric naphthoquinone monoacetal mediated by the monosodium salt of 1,2-ethanedithiol. Bicyclo[3.2.1]octadienones may serve as key core units in the synthesis of biologically relevant naphthocyclinones.
- Ando, Yoshio,Hori, Subaru,Fukazawa, Takumi,Ohmori, Ken,Suzuki, Keisuke
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supporting information
p. 9650 - 9653
(2015/08/11)
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- Studies on synthesis of quinonylidene Hoveyda-type complexes
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In a quest of redox-switchable metathesis catalysts we attempted synthesis of ruthenium quinonylidene complexes using two synthetic pathways. First, Hoveyda-type complexes bearing chelating benzylidene and naphthylidene ligands substituted with two alkoxy/hydroxy groups were synthesized and characterized. The catalysts were tested in model ring-closing metathesis reactions, and displayed interesting correlations between structure and catalytic activity. Unfortunately, numerous attempts at oxidation of the complexes to derivatives of benzo- and naphthoquinone were unsuccessful. However, the second approach, using exchange reaction of ruthenium precursor with vinylquinone ligand, gave a transient unstable product observed with 1H NMR. The experimental data suggest that conjugation of electron-deficient quinones to the ruthenium centre results in intrinsically unstable species, which undergo secondary reactions under ambient conditions.
- Grudzień, Krzysztof,Barbasiewicz, Micha?
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p. 322 - 327
(2015/04/27)
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- Characterization of a Rh(III) porphyrin-CO complex: Its structure and reactivity with an electron acceptor
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To analyse the electrocatalytic oxidation of carbon monoxide by Rh porphyrins, we isolated a CO-adduct of Rh octaethylporphyrin, and examined its properties and reactivity by IR, NMR, and X-ray crystallographic analyses. The results indicate that the CO adduct of Rh octaethylporphyrin is vulnerable to nucleophilic attack by H2O. The CO-adduct was easily oxidized by an electron acceptor (1,4-naphthoquinone) to generate CO2. This indicates that CO is sufficiently activated in the CO complex of Rh octaethylporphyrin to reduce an electron acceptor. This mechanism is in contrast to that for the CO oxidation by Pt-based electrocatalysts.
- Yamazaki, Shin-Ichi,Yao, Masaru,Asahi, Masafumi,Sato, Hiroyasu,Yamano, Akihito,Ioroi, Tsutomu
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supporting information
p. 13823 - 13827
(2015/08/18)
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- Role of substituents on the reactivity and product selectivity in reactions of naphthalene derivatives catalyzed by the orphan thermostable cytochrome P450, CYP175A1
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The thermostable nature of CYP175A1 enzyme is of potential interest for the biocatalysis at ambient temperature or at elevated temperature under environmentally benign conditions. Although little is known about the substrate selectivity of this enzyme, the biocatalytic activities of CYP175A1 on different substituted naphthalenes have been studied in oxidative pathway, and the effect of the substituent on the reaction has been determined. The enzyme first acts as a peroxygenase to convert these substituted naphthalenes to the corresponding naphthols, which subsequently undergo in-situ oxidative dimerization to form dyes of different colors possibly by the peroxidase-type activity of CYP175A1. The product analyses and kinetic measurements suggested that the presence of electron releasing substituent (ERS) in the substrate enhanced the substrate conversion, whereas the presence of electron withdrawing substituent (EWS) in the substrate drastically reduced the substrate conversion. The position of the ERS in the substrate was also found to play an important role in the transformation of the substrate. The results further demonstrate that mutation of the Leu80 residue to Phe enhances the reactivity of the enzyme by favoring the substrate association in the active site. The observed rates of the enzymatic oxygenation reaction of the substituted naphthalenes followed the Hammett correlation of substituent effect, supporting aromatic electrophilic substitution mechanism catalyzed by the cytochrome P450 enzyme.
- Banerjee, Shibdas,Goyal, Sandeep,Mazumdar, Shyamalava
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- Facile synthesis of mollugin by kinetic control and anti-HCV (Hepatitis C Virus) activity of its analogues
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Mollugin has been reported to have various biological activities including antineoplastic, antitumor, antiviral against the hepatitis B virus, anti-aging and antimutagenic activities. An effective and concise synthesis of mollugin in two steps including kinetic control from the cheap starting material 1,4-naphthoquinone has been introduced, and mollugin derivatives thus prepared are screened for their inhibition ability against the hepatitis C virus (HCV) and the dihydrobenzochromene structure might be an additional anti-HCV agent as a new leading compound.
- Choi, Da Hye,Lee, Na Ri,Kim, Cheol Gi,Kim, Jong Woo,Lee, Sang Wook,Jun, Jong-Gab
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p. 3232 - 3238
(2015/04/22)
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- Rabbit 3-hydroxyhexobarbital dehydrogenase is a NADPH-preferring reductase with broad substrate specificity for ketosteroids, prostaglandin D2, and other endogenous and xenobiotic carbonyl compounds
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3-Hydroxyhexobarbital dehydrogenase (3HBD) catalyzes NAD(P) +-linked oxidation of 3-hydroxyhexobarbital into 3-oxohexobarbital. The enzyme has been thought to act as a dehydrogenase for xenobiotic alcohols and some hydroxysteroids, but its physiological function remains unknown. We have purified rabbit 3HBD, isolated its cDNA, and examined its specificity for coenzymes and substrates, reaction directionality and tissue distribution. 3HBD is a member (AKR1C29) of the aldo-keto reductase (AKR) superfamily, and exhibited high preference for NADP(H) over NAD(H) at a physiological pH of 7.4. In the NADPH-linked reduction, 3HBD showed broad substrate specificity for a variety of quinones, ketones and aldehydes, including 3-, 17- and 20-ketosteroids and prostaglandin D2, which were converted to 3α-, 17β- and 20α-hydroxysteroids and 9α,11β- prostaglandin F2, respectively. Especially, α-diketones (such as isatin and diacetyl) and lipid peroxidation-derived aldehydes (such as 4-oxo- and 4-hydroxy-2-nonenals) were excellent substrates showing low Km values (0.1-5.9 μM). In 3HBD-overexpressed cells, 3-oxohexobarbital and 5β-androstan-3α-ol-17-one were metabolized into 3-hydroxyhexobarbital and 5β-androstane-3α,17β-diol, respectively, but the reverse reactions did not proceed. The overexpression of the enzyme in the cells decreased the cytotoxicity of 4-oxo-2-nonenal. The mRNA for 3HBD was ubiquitously expressed in rabbit tissues. The results suggest that 3HBD is an NADPH-preferring reductase, and plays roles in the metabolisms of steroids, prostaglandin D2, carbohydrates and xenobiotics, as well as a defense system, protecting against reactive carbonyl compounds.
- Endo, Satoshi,Matsunaga, Toshiyuki,Matsumoto, Atsuko,Arai, Yuki,Ohno, Satoshi,El-Kabbani, Ossama,Tajima, Kazuo,Bunai, Yasuo,Yamano, Shigeru,Hara, Akira,Kitade, Yukio
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p. 1366 - 1375
(2013/11/19)
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- Solar photochemistry: Optimisation of the photo Friedel-Crafts acylation of naphthoquinones
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A practical and robust photo Friedel-Crafts acylation of naphthoquinones is described. Although the reaction proceeds slowly in sunlight, the optimised conditions offer a substantial improvement to those already reported, by the utilisation of a more reliable and practical 'sun-mimicking' light source, a less hazardous solvent system (trifluorotoluene) and faster reaction times. Using these conditions, the reaction scope has been expanded to include functionalised aldehyde and naphthoquinone substrates, affording the desired photo-products in acceptable to excellent yields (17-81%). Factors influencing the regiochemistry of the photo Friedel-Crafts reaction on unsymmetrical naphthoquinones have also been investigated.
- Mitchell, Lorna J.,Lewis, William,Moody, Christopher J.
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p. 2830 - 2842
(2013/10/08)
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- Synthesis of pentalongin and C(1)- and C(3)-substituted pentalongin using intramolecular Heck reaction
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An efficient and high yielding route for the synthesis of pentalongin and 1-alkyl, 1-aryl, and 3-alkyl substituted pentalongin has been demonstrated using intramolecular Heck reaction as a key step.
- Nandi, Sukla,Singha, Raju,Samanta, Shubhankar,Ray, Jayanta K.
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scheme or table
p. 2659 - 2661
(2012/07/02)
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- Regioselective iridium(I)-catalysed remote borylation of oxygenated naphthalenes
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We present our investigations into the regioselective borylation and halogenation of polyoxygenated naphthalene systems that are key precursors to dimeric pyranonaphthoquinone natural products. A variety of oxygenated naphthalenes were successfully borylated with pinacolborane in high yield and excellent regioselectivity using [Ir(COD)OMe]2 and di-tert-butylbipyridine (dtbpy). The boronates were also readily transformed into the corresponding halides, opening new avenues for the preparation of advanced Suzuki coupling substrates useful for the synthesis of natural products.
- Hume, Paul,Furkert, Daniel P.,Brimble, Margaret A.
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experimental part
p. 3771 - 3773
(2012/10/07)
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- Multitargeted drug development: Discovery and profiling of dihydroxy substituted 1-aza-9-oxafluorenes as lead compounds targeting Alzheimer disease relevant kinases
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Alzheimer disease (AD) turned out to be a multifactorial process leading to neuronal decay. So far merely single target structures which attribute to the AD progression have been considered to develop specific drugs. However, such drug developments have been disappointing in clinical stages. Multitargeting of more than one target structure determines recent studies of developing novel lead compounds. Protein kinases have been identified to contribute to the neuronal decay with CDK1, GSK-3β and CDK5/p25 being involved in a pathological tau protein hyperphosphorylation. We discovered novel lead structures of the dihydroxy-1-aza-9-oxafluorene type with nanomolar activities against CDK1, GSK-3β and CDK5/p25. Structure-activity relationships (SAR) of the protein kinase inhibition are discussed within our first compound series. One nanomolar active compound profiled as selective protein kinase inhibitor. Bioanalysis of a harmless cellular toxicity and of the inhibition of tau protein phosphorylation qualifies the compound for further studies.
- Tell, Volkmar,Mahmoud, Kazem Ahmed,Hilgeroth, Andreas,Holzer, Max,Herrmann, Lydia,Schaechtele, Christoph,Totzke, Frank
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p. 6914 - 6918,5
(2020/09/02)
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- Design and synthesis of novel quinone inhibitors targeted to the redox function of apurinic/apyrimidinic endonuclease 1/redox enhancing factor-1 (Ape1/Ref-1)
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The multifunctional enzyme apurinic endonuclease 1/redox enhancing factor 1 (Ape1/ref-1) maintains genetic fidelity through the repair of apurinic sites and regulates transcription through redox-dependent activation of transcription factors. Ape1 can therefore serve as a therapeutic target in either a DNA repair or transcriptional context. Inhibitors of the redox function can be used as either therapeutics or novel tools for separating the two functions for in vitro study. Presently there exist only a few compounds that have been reported to inhibit Ape1 redox activity; here we describe a series of quinones that exhibit micromolar inhibition of the redox function of Ape1. Benzoquinone and naphthoquinone analogues of the Ape1-inhibitor E3330 were designed and synthesized to explore structural effects on redox function and inhibition of cell growth. Most of the naphthoquinones were low micromolar inhibitors of Ape1 redox activity, and the most potent analogues inhibited tumor cell growth with IC50 values in the 10-20 μM range.
- Nyland II, Rodney L.,Luo, Meihua,Kelley, Mark R.,Borch, Richard F.
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experimental part
p. 1200 - 1210
(2010/07/18)
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- Green photochemistry: Photo-Friedel-Crafts acylations of 1,4-naphthoquinone in room temperature ionic liquids
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The photo-Friedel-Crafts acylation of 1,4-naphthoquinone with various aldehydes was investigated in a series of room temperature ionic liquids. High conversions and selectivities were achieved in [C2mim] +-based ionic liquids with the highest isolated yields found in [C2mim][NTf2]. The developed procedure allowed for a replacement of hazardous solvents such as benzene and acetonitrile which are commonly used for this transformation. The Royal Society of Chemistry 2009.
- Murphy, Brian,Goodrich, Peter,Hardacre, Christopher,Oelgemoeller, Michael
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experimental part
p. 1867 - 1870
(2011/02/24)
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- Photolytic transformations of p-quinones
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Quantum yields, apparent photolysis rate constants, and energies of activation of the dark stages in the decomposition of 3,6-di-tert-butyl-2,3- epoxy-5-hydroxycyclohex-2-ene-1,4-dione, 1,4-naphthoquinone, and 9,10-anthraquinone under irradiation at λ 313 nm and of 1,4-benzoquinone under irradiation at λ 232-254 nm were determined. Products of photochemical transformations of these compounds in saturated hydrocarbons were identified, and a probable mechanism of these transformations was proposed.
- Mishchenko,Maslennikov,Spirina,Kurskii,Faerman,Maslennikov
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body text
p. 1529 - 1532
(2009/06/28)
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- Synthesis and cytotoxicity of analogues of the marine secondary metabolite, 2-deoxylapachol
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The syntheses of four 2-substituted 1,4 naphthoquinones, related to the marine natural product 2-deoxylapachol, are reported. All four synthetic compounds were cytotoxic to WHCO1 oesophageal cancer cells.
- Sunassee, Suthananda N.,Van Wyk, Albert W.W.,Osoniyi, Omolaja,Hendricks, Denver T.,Davies-Coleman, Michael T.
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p. 677 - 679
(2008/09/20)
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- Simple, mild, and efficient method for the reduction of 1,4-benzoquinones to hydroquinones by the action of NaN3
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A simple, mild, and efficient method is presented for the reduction of 1,4-benzoquinones to hydroquinones by the action of NaN3 under neutral conditions in the presence of water. Copyright Taylor & Francis Group, LLC.
- Algi, Fatih,Balci, Metin
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p. 2293 - 2297
(2007/10/03)
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- Syntheses of soluble, π-stacking tetracene derivatives
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The syntheses of a series of fluorine- and alkyl/alkoxy-functionalized tetracenes are reported. These functional groups are found to improve the solubility in common organic solvents and tune molecular arrangement in solids. The crystal packing, electrochemical behavior, and UV-vis absorbance spectroscopy of these materials are discussed.
- Chen, Zhihua,Muller, Peter,Swager, Timothy M.
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p. 273 - 276
(2007/10/03)
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- Photodimers of a soluble tetracene derivative. Excimer fluorescence from the head-to-head isomer
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Equation presented. Irradiation of 5,12-didecyloxytetracene (1) leads to photodimers P1 (planosymmetric) and P2 (centrosymmetric). P1 is characterized by naphthalene excimer fluorescence, whereas P2 emits naphthalene monomer fluorescence.
- Reichwagen, Jens,Hopf, Henning,Del Guerzo, Andre,Desvergne, Jean-Pierre,Bouas-Laurent, Henri
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p. 1899 - 1902
(2007/10/03)
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- Synthesis of the o-Quinones and Other Oxidized Metabolites of Polycyclic Aromatic Hydrocarbons Implicated in Carcinogenesis
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Efficient new syntheses of the o-quinone derivatives of benzo[a]pyrene (BPQ), 7,12-dimethylbenz-[a] anthracene (DMBAQ), and benz[a]anthracene (BAQ), implicated as active carcinogenic metabolites of the parent polycyclic aromatic hydrocarbons (PAHs), are reported. These PAH quinones also serve as starting compounds for the synthesis of the other active metabolites of these PAHs thought to be involved in their mechanism(s) of carcinogenesis. The latter include the corresponding o-catechols, trans-dihydrodiols, and the corresponding anti- and syn-diol epoxides.
- Harvey, Ronald G.,Dai, Qing,Ran, Chongzhao,Penning, Trevor M.
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p. 2024 - 2032
(2007/10/03)
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- Immobilization of a Metal Complex in Y-Zeolite Matrix: Synthesis, X-ray Single-Crystal, and Catalytic Activities of a Copper (Schiff-Base)-Y Zeolite Based Hybrid Catalyst
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A new zeolite-immobilized copper(II) complex catalyst has been prepared by entrapping [CuL] [LH2 = N,N′ -(1,1-dimethylethylene)bis(salicylaldiimine)] on NaY zeolite matrix. The reaction of Cu-NaY and molten LH2 affords a green mass of crude catalyst that upon a treatment with CH3CN gives a gray-colored hybrid catalyst (CuL-NaY). The prepared catalyst has been characterized by IR and UV-vis spectroscopic and EPR spectrometric measurements, TG-DTA analysis, powder X-ray diffraction, and surface-area measurements. To ascertain the structure of the immobilized complex, a single-crystal X-ray diffraction analysis of [CuL] was performed. Spectroscopic measurements showed that the green crude of CuL-NaY contains a penta- or hexa-coordinated copper(II) moiety, while the CuL-NaY catalyst contains a distorted square-planar [CuL] complex moiety. A remarkable catalytic activity of the prepared hybrid catalyst has been observed in oxidation reactions of 1-naphthol and norbornene.
- Saha, Pratap Kumar,Banerjee, Surajit,Saha, Sandip,Mukherjee, Alok Kumar,Sivasanker, Subramanian,Koner, Subratanath
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p. 709 - 714
(2007/10/03)
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- One-pot synthesis of 12-hydroxy-12H-benzo[6]thioxanthene-6,11-diones from 1,4-naphthoquinone and o-acylbenzenethiols
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The title benzo[b]thioxanthenequinone derivatives could be prepared in one-pot via a sequential conjugate addition and an aldol-type reaction between 1,4-naphthoquinone and o-acylbenzenethiols, followed by oxidation with 1,4-naphthoquinone or air.
- Kobayashi, Kazuhiro,Umakoshi, Hironobu,Matsunaga, Akihiro,Tanmatsu, Miyuki,Morikawa, Osamu,Konishi, Hisatoshi
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p. 2095 - 2096
(2007/10/03)
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- Recyclable organotungsten Lewis acid and microwave assisted Diels-Alder reactions in water and in ionic liquids
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The water-soluble, organotungsten Lewis acid, [OP(2-py)3W(CO) (NO)2](BF4)2 (1), was synthesized and characterized. A series of 1-catalyzed Diels-Alder reactions were investigated under conventional heating or microwave heating conditions. The cycloaddition reactions were efficiently conducted in either water or in an ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate. The ionic liquid acts as a powerful medium not only for rate- and selectivity enhancements but also for facilitating catalyst recycling. Dramatic rate acceleration via microwave flash heating as compared to thermal heating was observed. Graphical Abstract
- Chen, I-Hon,Young, Jun-Nan,Yu, Shuchun Joyce
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p. 11903 - 11909
(2007/10/03)
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- Disubstituted lavendustin a analogs and pharmaceutical compositions comprising the analogs
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Disubstituted lavendustin A analogs that are PTK inhibitors having antiproliferative activity are described. Preferred compounds of the present invention, without limitation, satisfy either Formula 1 or Formula 2. Currently preferred compounds ,based on in vivo biological activity, are 4'-adamantylbenzoate-1'-N-1,4-dihydroxybenzylamine and 4'-adamantylmethylbenzoate-1'-N-1,4-dihydroxybenzylamine. The present invention also provides pharmaceutical compositions comprising effective amounts of disubstituted lavendustin A analogs. Such compositions also may comprise other active ingredients, other materials conventionally used in the formulation of pharmaceutical composition, and mixtures thereof. The compounds and compositions of the present invention can be used for treating subjects to, for example, inhibit the proliferation of living cells in the treatment of proliferative diseases.
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- Process for functionalising a phenolic compound carrying an electron-donating group
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The invention concerns a method for functionalizing a phenolic compound bearing an electron-donor group, in said group para position, inter alia a method for the amidoalkylation of a phenolic compound bearing an electron-donor group, and more particularly, a phenolic compound bearing an electron-donor group preferably, in the hydroxyl group ortho position. The method for functionalizing in para position with respect to an electron-donor group carried by a phenolic compound is characterised in that the phenolic compound bearing an electron-donor group is subjected to the following steps: a first step which consists of protecting the hydroxyl group in the form of a sulphonic ester function; a second step which consists in reacting the protected phenolic compound with an electrophilic reagent; optionally, a third step deprotecting the hydroxyl group.
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- Synthesis of hexagonal and cubic super-microporous niobium phosphates with anion exchange capacity and catalytic properties
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Super-microporous hexagonal niobium phosphate synthesized using neutral surfactant (S0I0 mechanism) and cubic structure with cationic surfactant (S+X-I+); the hexagonal niobium phosphate possesses an excellent anion exchange capacity (6.3 mmol g-1) and high product selectivity towards 4-naphthaquinone (88.6%) in the oxidation of 1-naphthol in presence of aqueous H2O2.
- Mal, Nawal Kishor,Fujiwara, Masahiro
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p. 2702 - 2703
(2007/10/03)
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- Polymer electrolyte and process for producing the same
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A polymer electrolyte having, in a main chain, a structural unit represented by the following formula (1):-[Ar1-(SO2-N-(X+)-SO2-Ar2)m-SO2-N-(X+)-SO2-Ar1-O]- wherein Ar1 and Ar2 independently represent a divalent aromatic groups, m represents an integer of 0 to 3, and X+ represents an ion selected from hydrogen ion, an alkali metal ion and ammonium ion, which is excellent in proton conductivity, thermal resistance and strength. The polymer electrolyte is soluble in solvents and has excellent film forming property and recycling efficiency.
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- Novel seco cyclopropa[c]pyrrolo[3,2-e]indole bisalkylators bearing a 3,3′-arylenebisacryloyl group as a linker
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We synthesized the novel seco cyclopropa[c]pyrrolo[3,2-e]indole (CPI) bisalkylators and evaluated their antitumor activity. Among these derivatives, 11a (AT-760), in which the two seco 3-methoxycarbonyl-2-trifluoromethyl CPI (MCTFCPI) moieties are connected with a 3,3′-(1,4-phenylene)bisacryloyl group, was found to exhibit more potent cytotoxicity and antitumor activity against HeLaS3 human uterine cervix carcinoma cells and Colon 26 adenocarcinoma cells, respectively, than 8 (bizelesin, U-77,779). It also appeared that compound 11a exhibits improved in vivo efficacy in the human colon CX-1 model when compared to either compound 8 or mitomycin C (MMC). Efficacious doses for 11a were found to be 2-fold lower than those for 8.
- Fukuda,Seto,Furuta,Ebisu,Oomori,Terashima
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p. 1396 - 1406
(2007/10/03)
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- N,N-bis(quinonyl)amines; synthesis and X-ray structure
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The preparation of several symmetrical and nonsymmetrical N,N-bis(quinonyl)amines is reported. These compounds, which have two quinones separated by one amino group, were obtained by an unexpected reaction of primary or secondary substituted aminoquinones
- Bittner, Shmuel,Meenakshi, Chandran,Temtsin, Galina
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p. 7423 - 7429
(2007/10/03)
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- Regioselective hydrolysis of diacetoxynaphthalenes catalyzed by Pseudomonas sp. lipase in an organic solvent
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Depending on the relative positions of the acetyl groups in the aromatic rings, the Pseudomonas sp. lipase-catalyzed hydrolysis of diacetoxynaphthalenes in tert-butylmethyl ether proceeds regioselectively to afford the corresponding monoacetates.
- Ciuffreda, Pierangela,Casati, Silvana,Santaniello, Enzo
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p. 317 - 321
(2007/10/03)
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