- Discovery and Optimization of a Selective Ligand for the Switch/Sucrose Nonfermenting-Related Bromodomains of Polybromo Protein-1 by the Use of Virtual Screening and Hydration Analysis
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Bromodomains (BRDs) are epigenetic interaction domains currently recognized as emerging drug targets for development of anticancer or anti-inflammatory agents. In this study, development of a selective ligand of the fifth BRD of polybromo protein-1 (PB1(5)) related to switch/sucrose nonfermenting (SWI/SNF) chromatin remodeling complexes is presented. A compound collection was evaluated by consensus virtual screening and a hit was identified. The biophysical study of protein-ligand interactions was performed using X-ray crystallography and isothermal titration calorimetry. Collective data supported the hypothesis that affinity improvement could be achieved by enhancing interactions of the complex with the solvent. The derived SAR along with free energy calculations and a consensus hydration analysis using WaterMap and SZmap algorithms guided rational design of a set of novel analogues. The most potent analogue demonstrated high affinity of 3.3 μM and an excellent selectivity profile, thus comprising a promising lead for the development of chemical probes targeting PB1(5).
- Myrianthopoulos, Vassilios,Gaboriaud-Kolar, Nicolas,Tallant, Cynthia,Hall, Michelle-Lynn,Grigoriou, Stylianos,Brownlee, Peter Moore,Fedorov, Oleg,Rogers, Catherine,Heidenreich, David,Wanior, Marek,Drosos, Nikolaos,Mexia, Nikitia,Savitsky, Pavel,Bagratuni, Tina,Kastritis, Efstathios,Terpos, Evangelos,Filippakopoulos, Panagis,Müller, Susanne,Skaltsounis, Alexios-Leandros,Downs, Jessica Ann,Knapp, Stefan,Mikros, Emmanuel
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Read Online
- Isoquinolinedione-urea hybrids: Synthesis, antibacterial evaluation, drug-likeness, molecular docking and DFT studies
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In the present study, we applied the molecular hybridization approach to combine isoquinolinedione and urea pharmacophores in the same molecules. The hybrid compounds (IU1-IU14) were obtained by the reaction of 2-aminohomophthalimide and an equivalent amount of various isocyanate derivatives. After confirming the chemical structures and evaluating drug-likeness properties, the synthesized compounds were examined for their antibacterial activities against a wide range of bacteria. The compounds possessing lipophilic halogen substituents showed better activities against Gram-positive bacteria, particularly on Staphylococcus aureus strains. This activity trend was further supported by molecular docking studies in the ATP pocket of S. aureus DNA gyrase. Several important parameters such as, ionization potential (IP), electron affinity (EA), global chemical hardness (η), global softness (σ), and electronegativity (χ) were carried out to gain insights into the structural properties and stabilities of selected active compounds by means of density functional theory (DFT) at the B3LYP functional using basis set B3LYP/6–311G(d,p). Electrostatic potential maps (ESPs) and frontier orbital visualizations were further used to comment on molecular polarity and stability.
- ?zkul, Ceren,Dengiz, Cagatay,Do?an, ?engül Dilem,Gündüz, Miyase G?zde,Han, M. ?hsan,K?prü, Semiha
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- Unexpected formal [4 + 2]-cycloaddition of chalcone imines and homophthalic anhydrides: preparation of dihydropyridin-2(1H)-ones
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A series of medicinally important dihydropyridin-2(1H)-ones have been preparedviaa novel [4 + 2]-formal cycloaddition reaction of chalcone imines and homophthalic anhydrides, which is a rare example of lactam construction from an imine acting as a four-atom building block. In contrast to previous studies on the reactivity of homophthalic anhydrides towards similar substrates,N-tosyl chalcone imines, we found the possibility of switching chemoselectivity by changing substituents at the nitrogen atom, which leads to the formation of heterocycles instead of the expected carbocycles. This reaction is very similar in appearance to the classic 1,2-addition of cyclic anhydrides to imines, often referred to as the Castagnoli-Cushman reaction, but differs in mechanistic details (representing a 1,4-reaction of imine). The developed atom-economical, stereoselective and catalyst- and chromatography-free protocol provided facile access to 28 structurally diverse heterocyclic products (in up to 88% yield) including synthetically challenging annelated tricyclic and previously unreported pentaaryl-substituted dihydropyridin-2(1H)-ones.
- Guranova, Natalia,Golubev, Pavel,Bakulina, Olga,Dar'in, Dmitry,Kantin, Grigory,Krasavin, Mikhail
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supporting information
p. 3829 - 3833
(2021/05/14)
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- Facile access to Fe(III)-complexing cyclic hydroxamic acids in a three-component format
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Cyclic hydroxamic acids can be viewed as effective binders of soluble iron and can therefore be useful moieties for employing in compounds to treat iron overload disease. Alternatively, they are analogs of bacterial siderophores (iron-scavenging metabolites) and can find utility in designing antibiotic constructs for targeted delivery. An earlier described three-component variant of the Castagnoli—Cushman reaction of homophthalic acid (via in situ cyclodehydration to the respective anhydride) was extended to involve hydroxylamine in lieu of the amine component of the reaction. Using hydroxylamine acetate and O-benzylhydroxylamine was key to the success of this transformation due to greater solubility of the reagents in refluxing toluene (compared to hydrochloride salt). The developed protocol was found suitable for multigram-scale syntheses of N-hydroxy- and N-(benzyloxy)tetrahydroisoquinolonic acids. The cyclic hydroxamic acids synthesized in the newly developed format have been tested and shown to be efficient ligands for Fe3+, which makes them suitable candidates for the above-mentioned applications.
- Chupakhin, Evgeny,Bakulina, Olga,Dar’in, Dmitry,Krasavin, Mikhail
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- Highly Enantio- and Diastereoselective Catalytic Asymmetric Tamura Cycloaddition Reactions
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The first broad-scope catalytic asymmetric Tamura cycloaddition reactions are reported. Under the influence of anion-binding bifunctional catalysis a wide range of α,β-unsaturated N-trityl imines undergo reactions with enolisable anhydrides to form highly synthetically useful α-tetralone structures with excellent enantio- and -diastereocontrol. In stark contrast to the previous literature benchmarks, doubly activated or highly electron deficient alkenes are not required. A facile two-step, high yielding sequence can convert the cycloadducts to α-haloketones (challenging to generate catalytically by other means) with the net formation of two new C?C bonds and three new contiguous stereocentres with exquisite stereocontrol. A DFT study has provided insight into the catalyst mode of action and the origins of the observed enantiocontrol.
- Collar, Aarón Gutiérrez,Trujillo, Cristina,Connon, Stephen J.
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supporting information
p. 7270 - 7274
(2019/05/15)
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- The base-catalysed Tamura cycloaddition reaction: Calculation, mechanism, isolation of intermediates and asymmetric catalysis
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A combined experimental and computational investigation has revealed that the base-catalysed Tamura cycloaddition between homophthalic anhydride and activated alkenes/alkynes-a reaction previously thought of as a Diels-Alder type process-proceeds via a stepwise mechanism involving conjugate addition and ring closure; which allowed the first catalytic asymmetric α-substitution reactions to be demonstrated with up to >99% ee.
- Lockett-Walters, Bruce,Trujillo, Cristina,Twamley, Brendan,Connon, Stephen
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supporting information
p. 11283 - 11286
(2019/09/30)
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- Catalytic Asymmetric Cycloadditions between Aldehydes and Enolizable Anhydrides: Cis-Selective Dihydroisocoumarin Formation
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In the presence of a trityl-substituted cinchona alkaloid-based catalyst, homophthalic, aryl succinic, and glutaconic anhydride derivatives reacted with aromatic and aliphatic aldehydes to produce cis-lactones in up to 90:10 dr and 99% ee. A DFT study has shown how the catalyst is uniquely able to bring about the opposite sense of diastereocontrol to that usually observed.
- Aiello, Maria Luisa,Farid, Umar,Trujillo, Cristina,Twamley, Brendan,Connon, Stephen J.
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p. 15499 - 15511
(2019/01/04)
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- Efficient cyclodehydration of dicarboxylic acids with oxalyl chloride
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Literature examples illustrating the use of oxalyl chloride to prepare dicarboxylic acid anhydrides are surprisingly limited. At the same time, we have discovered a method involving the use of this readily available reagent which allowed the preparation of novel cyclic anhydrides where other, more conventional, methods had failed. Herein, we demonstrate that the method is applicable to a wide diversity of substrates, delivers good to excellent yields of cyclic anhydrides without chromatographic purification and can be considered a synthetic tool of choice whenever dicarboxylic acid cyclodehydration is required.
- Kantin, Grigory,Chupakhin, Evgeny,Dar'in, Dmitry,Krasavin, Mikhail
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supporting information
p. 3160 - 3163
(2017/07/18)
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- Catalytic asymmetric Tamura cycloadditions involving nitroalkenes
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The first examples of asymmetric Tamura cycloaddition reactions involving singly activated alkenes are reported. Homophthalic anhydride reacts with α-methyl nitrosytrenes in the presence of an alkaloid-based catalyst to generate fused bicyclic aromatic ketone products with three new stereocentres (which are susceptible to subsequent equilibration) in 12-99% ee. An unusual equilibration process which occurs in methanolic medium in the absence of a recognisable base via proton transfer at the α-carbon of an ester was investigated experimentally and computationally.
- Manoni, Francesco,Farid, Umar,Trujillo, Cristina,Connon, Stephen J.
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p. 1463 - 1474
(2017/02/15)
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- Expeditious Synthesis of the Topoisomerase i Inhibitors Isoindolo[2,1- b ]isoquinolin-7(5 H)-one and the Alkaloid Rosettacin Based on Aryl Radical Cyclization of Enamide Generated by Using N -Acylaiminium Chemistry
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A short and effective approach to the synthesis of the topoisomerase I inhibitor isoindolo[2,1-b]isoquinolin-7(5H)-one and the alkaloid rosettacin belonging to the aromathecin family is presented. The key step of this sequence, which resulted in the formation of a five-membered ring, was the aryl radical cyclization of enamides generated using N-acyliminium chemistry.
- El Blidi, Lahssen,Namoune, Aurélie,Bridoux, Alexandre,Nimbarte, Vijaykumar D.,Lawson, Ata Martin,Comesse, Sébastien,Da?ch, Adam
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p. 3583 - 3592
(2015/11/18)
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- Chiral Pool-Based Synthesis of Naphtho-Fused Isocoumarins
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A variety of chiral derivatives of benzo[d]naphtho[1,2-b]pyran-6-one were prepared in a single step by Et3N-mediated condensation of homophthalic anhydride with different derivatives of (S)-amino acid chlorides at -5 °C by employing a chiral pool methodology. Chirality 27:951-957, 2015.
- Raza, Abdul Rauf,Saddiqa, Aisha,?akmak, Osman
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p. 951 - 957
(2015/11/16)
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- Catalytic asymmetric tamura cycloadditions
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In the presence of a novel, tert-butyl-substituted squaramide-based catalyst, enolizable anhydrides react with alkylidene oxindoles to generate spirooxindole products of significant synthetic interest with excellent enantio- and diastereocontrol. The methodology is of wide scope and encompasses both homophthalic and glutaconic anhydride derivatives, which lead to structurally diverse products. Glutaconic acid-derived anhydrides undergo a clean post-cyclization decarboxylation process which is not a feature of reactions involving homophthalic acid-derived anhydrides. The unusual influence of reaction temperature on diastereocontrol has been probed, with reactions occurring at 30 °C and -30 °C delivering products epimeric at one stereocenter only, in near optical purity. Squared away: The first strategy for bringing about enantioselective Tamura reactions is reported. In the presence of a squaramide-based catalyst, enolizable anhydrides react with alkylidene oxindoles to generate spirooxindole products with excellent enantio- and diastereocontrol. The methodology is of wide scope and leads to structurally diverse products.
- Manoni, Francesco,Connon, Stephen J.
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supporting information
p. 2628 - 2632
(2014/03/21)
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- Design, synthesis and docking studies of some novel isocoumarin analogues as antimicrobial agents
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A number of novel isocoumarin analogues have been synthesized by the condensation of homophthalic acid anhydride with different non-steroidal anti-inflammatory drugs (NSAIDs). To investigate the antimicrobial data on a structural basis, in silico docking studies of the synthesized compounds (4a-4g) into the crystal structure of UDP-N-acetylmuramate-l-alanine ligase using an Autodock PyRx virtual screening program were performed in order to predict the affinity and orientation of the synthesized compounds at the activities. UDP-N-acetylmuramate-l-alanine ligase is essential for d-glutamate metabolism and peptidoglycan biosynthesis in bacteria. R2 values showed good agreement with predicted binding affinities obtained by molecular docking studies. The results indicate that the basic nucleic portion of the (4c), (4g), (4f) and (4a) binds into the specificity pocket. In this pocket, the isocoumarin nucleus of these compounds interacts with the amino acid residue of the target. Moreover, it is verified by in vitro antimicrobial screening, in which all of the compounds were active against tested bacterial strains. Among these compounds (4c), (4g), (4f) and (4a) showed good bacterial zone inhibition. This journal is
- Ashraf, Zaman,Saeed, Aamer,Nadeem, Humaira
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p. 53842 - 53853
(2015/02/19)
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- Synthesis and antitumor activity evaluation of 2-arylisoquinoline-1,3(2H, 4H)-diones in vitro and in vivo
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Six 2-(2-acylaminobenzothiazol-6-yl)isoquinoline-1,3(2H,4H)-diones (1a-1f) and five 2-arylisoquinoline-1,3(2H,4H)-diones (1g-1k) were synthesized by refluxing homophthalic anhydrides with 2-acylaminobenzothiazolyl-6-amine or substituted aniline in glacial acetic acid. The cytotoxic activities of 1a-1k were evaluated via MTT method against A431, A549, and PC3. Compound 1b relatively displayed a higher cytotoxic activity than the others. The antitumor effect of 1b were evaluated in established nude mice PANC-1 xenograft model. The results suggest that compound 1b could potentially inhibit tumor growth.
- Kang, Bo-Rui,Wang, Juan,Li, Huan,Li, Yan,Mei, Qi-Bing,Zhang, San-Qi
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p. 1340 - 1349
(2014/03/21)
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- INDENOISOQUINOLINONE DERIVATIVES, MANUFACTURING METHOD AND MEDICAL USE THEREOF
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Indenoisoquinolinone derivatives (I), the manufacturing method and the medical use thereof, which belong to pharmaceutical chemistry and organic chemistry field, are disclosed. These compounds can be used for treating several medical symptoms related to postmenopausal syndrome, uterine fibers deterioration and aortic smooth muscle cells proliferation, especially ER-(+) depend breast cancer. Meanwhile, these compounds can also be used for treating glioma and lung cancer, and have inhibiting effect on tumor metastasis effect on tumor metastasis.
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Paragraph 0040
(2013/04/13)
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- Synthesis of fused tetrazolone derivatives
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New fused tetrazolone derivatives were synthesized using homophthalic and maleic anhydrides. Treatment of anhydrides with trimethylsilyl azide opened the lactone rings and formed the corresponding intermediates, which bore 1,3-dipole and dipolarophile functionalities in ortho positions. The intermediates partially underwent internal 1,3-dipolar cycloaddition to produce fused tetrazolone derivatives. When the carbonyl groups in anhydride were not conjugated with any double bond, then a triazine-fused tetrazolone derivative was formed. TUeBITAK.
- Oezcan, Sevil,Ekmekci, Zeynep,Muejde, Berk,Balci, Metin
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p. 610 - 618
(2013/08/23)
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- Enantioselective organic anhydride reactions
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Disclosed herein is enantioselective synthetic method comprising reacting an enolisable C4-C50 organic anhydride with a second compound selected from the group consisting of an aldehyde, a ketone, an aldimine, a ketimine or a Michael Acceptor in the presence of a bifunctional organocatalyst. The reaction may find particular utility in the enantioselective synthesis of medicinally relevant heterocycles, such as dihydroisocoumarins and dihydroisoquinolinones.
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Paragraph 0070
(2013/09/26)
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- ENANTIOSELECTIVE ORGANIC ANHYDRIDE REACTIONS
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Disclosed herein is enantioselective synthetic method comprising reacting an enolisable C4-C50 organic anhydride with a second compound selected from the group consisting of an aldehyde, a ketone, an aldimine, a ketimine or a Michael Acceptor in the presence of a bifunctional organocatalyst. The reaction may find particular utility in the enantioselective synthesis of medicinally relevant heterocycles, such as dihydroisocoumarins and dihydroisoquinolinones.
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Page/Page column
(2013/09/26)
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- A catalytic asymmetric reaction involving enolizable anhydrides
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In the presence of a highly efficient novel bifunctional organocatalyst at low loadings under mild conditions, enolizable homophthalic anhydrides can be added to a range of aromatic and aliphatic aldehydes to give dihydroisocoumarins, with excellent yields and diastereo-and enantiocontrol (up to 99% ee).
- Cornaggia, Claudio,Manoni, Francesco,Torrente, Esther,Tallon, Sean,Connon, Stephen J.
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supporting information; experimental part
p. 1850 - 1853
(2012/06/16)
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- The chemistry of homophthalic acid: a new synthetic strategy for construction of substituted isocoumarin and indole skeletons
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Homophthalic acid was reacted with thionylchloride/DMF and chloroethylformate/NEt3 in the presence and absence of NaN3. In all cases completely different isocoumarin derivatives were obtained. These unusual isocoumarin derivatives were isolated and characterized and their formation mechanisms are discussed. The homophthalic acid monomethyl ester was converted into the corresponding isocyanate. Reaction of the isocyanate with different amines produced the urea derivatives. Base-supported condensation reactions of these products gave first an indolinone derivative, which underwent further intermolecular condensation to give substituted indole derivatives. However, when the condensation reaction was carried out in the presence of acetic anhydride, the intermolecular reactions were suppressed. This methodology opens up a new way of synthesizing of various five-membered ring substituted indole derivatives.
- ?zcan, Sevil,Balci, Metin
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p. 5531 - 5540
(2008/09/21)
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- Synthesis of diverse lactam carboxamides leading to the discovery of a new transcription-factor inhibitor
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(Chemical Equation Presented) Diversity is the key: Skeletal diversity is a useful starting point in the search for compounds that modulate protein-biopolymer interactions. A library of 400 lactam carboxamides has been synthesized in a short synthetic sequence and a new compound that inhibits the interaction of a transcription factor (HOXA13) with its DNA target has been discovered, and inhibition of transcription is demonstrated in cells.
- Ng, Pui Yee,Tang, Yuchen,Knosp, Wendy M.,Stadler, H. Scott,Shaw, Jared T.
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p. 5352 - 5355
(2008/03/27)
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- The synthesis of unusual isocoumarin derivatives: the chemistry of homophthalic acid
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Homophthalic acid was reacted with thionyl chloride/DMF and ethyl chloroformate/NEt3 in the presence and absence of NaN3. In all cases completely different isocoumarin derivatives were obtained. These unusual isocoumarin derivatives were characterized and their mechanism of formation is discussed.
- ?zcan, Sevil,?ahin, Ertan,Balci, Metin
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p. 2151 - 2154
(2008/02/04)
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- Ozonolysis of enol ethers. Part 10. Ozonization of enol ethers from 1,2- and 1,3-dicarbonyl compounds: Direct quantitative synthesis of phthalonic acid anhydride
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The results of ozonolyses of enol ethers from 1.2- and 1.3-dicarbonyl compounds presented here strongly indicate that these reactions do not proceed via the established Criegee ozonolysis mechanism for nucleophilic C=C bonds. The quantitative one-step synthesis of phthalonic acid anhydride via ozonolysis of 2-(methoxymethyliden)-1H-inden-1.3(2H)-dione (28a) is described. Furthermore, a revision of the theory of alkene ozonolysis in the presence of tetracyanoethylene (TCNE) is proposed on the basis of a single-electron-transfer (SET) chemistry.
- Schank, Kurt,Beck, Horst,Pistorius, Susanne
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p. 2025 - 2049
(2007/10/03)
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- Isoquinoline derivatives and isoquinoline combinatorial libraries
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The present invention provides the synthesis of heterocyclic compounds based on the isoquinoline ring. More specifically, the invention provides novel isoquinoline derivatives as well as novel libraries comprised of such compounds.
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- Isoquinoline compound melanocortin receptor ligands and methods of using same
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The invention relates to melanocortin receptor ligands and methods of using the ligands to alter or regulate the activity of a melanocortin receptor. The invention further relates to tetrahydroisoquinoline aromatic amines that function as melanocortin receptor ligands and as agents for controlling cytokine-regulated physiologic processes and pathologies, and combinatorial libraries thereof.
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- Isoquinoline derivatives and isoquinoline combinatorial libraries
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The present invention provides the synthesis of heterocyclic compounds based on the isoquinoline ring. More specifically, the invention provides novel isoquinolines as well as novel libraries comprised of many such compounds, and methods of synthesizing the libraries.
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- ISOQUINOLINE DERIVATIVES AND ISOQUINOLINE COMBINATORIAL LIBRARIES
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The present invention provides the synthesis of heterocyclic compounds based on the isoquinoline ring. More specifically, the invention provides novel isoquinolines as well as novel libraries comprised of many such compounds, and methods of synthesizing the libraries.
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- Heterocyclic anthracycline analogs
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Novel pyrano heterocyclic anthracycline derivatives are described, which are useful in the treatment of cancer and tumors, such as breast cancer, leukemia, lung cancer, colon cancer, ovarian cancer, renal cancer, and melanoma. As well, these compounds may be used ex vivo for the treatment of cancerous bone marrow before retransplanting said marrow in a patient. Pharmaceutical compositions and methods of preparing the compounds are also described.
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- Clay catalysis: A convenient and rapid formation of anhydride from carboxylic acid and isopropenyl acetate under microwave irradiation
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The Montmorillonite KSF catalyses the synthesis of anhydrides from carboxylic acids in the presence of isopropenyl acetate under microwave irradiations.
- Villemin,Labiad,Loupy
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p. 419 - 424
(2007/10/02)
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- Facile and Efficient Syntheses of Carboxylic Anhydrides and Amides Using (Trimethylsilyl)ethoxyacetylene
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(Trimethylsilyl)ethoxyacetylene, a stable and easy-handling reagent, serves as an excellent dehydrating agent for the synthesis of carboxylic anhydrides and amides from the corresponding carboxylic acids.By means of this reagent, various types of acid-sensitive carboxylic anhydrides and amides were obtained almost in quantative yields.Twenty-two examples of carboxylic anhydrides and 12 examples of amides were presented.
- Kita, Yasuyuki,Akai, Shuji,Ajimura, Naomi,Yoshigi, Mayumi,Tsugoshi, Teruhisa,et al.
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p. 4150 - 4158
(2007/10/02)
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- A MILD AND FACILE SYNTHESIS OF CARBOXYLIC ANHYDRIDES
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Reaction of carboxylic acids with trimethylsilylethoxyacetylene in an inert solvent under mild conditions affords the corresponding carboxylic anhydrides in almost quantitative yields.
- Kita, Y.,Akai, S.,Yoshigi, M.,Nakajima, Y.,Yasuda, H.,Tamura, Y.
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p. 6027 - 6030
(2007/10/02)
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- Stereopopulation Control. 8. Rate and Equilibrium Enhancement in the Formation of Homophthalic Anhydrides
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The kinetics of cyclization of α,α,3,4,6-pentamethylhomophthalic acid have been measured in sovent acetonitrile at 28.5 deg C, using as catalysts a series of acids ranging in strength from perchloric to acetic.In the presence of 0.12 M HClO4, t1/2 for acid anhydride formation = 0.3 s.For the stronger acid catalysts, kcycl is a linear function of catalyst concentration; for the weak acids, however, a change in rate-limiting step is revealed by curvature in the plots of ktotobsd vs. .All the weak acids show the same limiting value, 6.45E-3 min-1; this value is considered to be the rate constant for uncatalyzed formation of the tetrahedral intermediate.Homoconjugate bases (HA2(-)) of the weak acids show a similar curvature in their dilution plots, and the same limiting rate constant as for weak acids.Two independent and competitive pathways for cyclization are proposed.For strong acid catalysis, an intermediate acylium ion is considered on the basis of Broensted α = -0.79, kH/kD ca. 1, and acceleration of anhydride hydrolysis by methyl substituents.A value of ΔSexcit. = -23 eu suggests that cyclization, rather than acylium ion formation, is rate limiting.For weak acid catalysis, α = -0.17, kH/kD = 4.3, ΔSexcit. = -31 eu, and methyl groups retard anhydride hydrolysis by electron release; for this pathway, catalyzed breakdown of a tetrahedral intermediate is considered rate limiting.The composite Broensted plot is curved because the two pathways follow different rate laws.In contrast to rate enhancement results for phenolic lactone formation, the pentamethylhomophthalic acid is only sevenfold as reactive as α,α-dimethylhomophthalic acid.For the catalyst acids, pK(acetonitrile) is shown to be a linear function of pK(H2O) over the entire range of acids examined.
- Hillery, Paul S.,Cohen, Louis A.
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p. 2760 - 2770
(2007/10/02)
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- Synthesis of Aromatic Carbonyl Compounds via Thallation-Carbonylation of Arenes
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Simple arenes, substituted benzylic and β-phenylethyl alcohols, benzoic acid, phenylacetic acid, benzamide, acetanilide, phenylurea, and benzophenone have been thallated under variety of reaction conditions with thallium(III) trifluoroacetate and subsequently carbonylated with 19percent PdCl2, 2 equiv of LiCl, and MgO in either methanol or tetrahydrofuran under 1 atm of carbon monoxide to give aromatic esters, substituted phthalides and 3,4-dihydroisocoumarins, phthalic and homophthalic anhydride, phthalimide, and the ortho-substituted methyl esters of acetanilide, phenylurea, and benzophenone, respectively.The scope and limitations of this approach to aromatic carbonyl compounds are examined.
- Larock, Richard C.,Fellows, Constance A.
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p. 1900 - 1907
(2007/10/02)
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- EFFICIENT DEMETYLATION OF METHYL ESTERS WITH ANHYDROUS TRIFLUOROACETIC ACID
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Trifluoroacetic acid (TFA) is an effective reagent for the demethylation of methyl esters under anhydrous conditions, affording the parent acids and methyl trifluoroacetate.
- Tabor, Derrick C.,Evans, Slayton A.,Kenan, William Rand
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p. 855 - 864
(2007/10/02)
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- Synthesis of Aromatic Esters, Lactones, Anhydrides, and Heterocycles via Thallation-Carbonylation of Arenes
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The thallation and subsequent palladium-catalyzed carbonylation of simple arenes, benzylic and β-phenethyl alcohols, benzoic and phenylacetic acids, benzamide, and acetanilide afford benzoate esters, phthalides, 3,4-dihydroisocoumarins, phthalic and homophthalic anhydrides, phthalimide, and acetylanthranil, respectively.The carbonylation reaction proceeds in excellent yield at room temperature and atmospheric pressure and is highly stereo- and regioselective.
- Larock, Richard C.,Fellows, Constance A.
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p. 363 - 365
(2007/10/02)
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