- One-Pot Synthesis and Conformational Analysis of Six-Membered Cyclic Iodonium Salts
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Two one-pot procedures for the construction of carbon-bridged diaryliodonium triflates and tetrafluoroborates are described. Strong Br?nsted acids enable the effective Friedel-Crafts alkylation with diversely substituted o-iodobenzyl alcohol derivatives, providing diphenylmethane scaffolds, which are subsequently oxidized and cyclized to the corresponding dibenzo[b,e]iodininium salts. Based on NMR investigations and density functional theory (DFT) calculations, we could verify the so-far-undescribed existence of two stable isomers in cyclic iodonium salts substituted with aliphatic side chains in the carbon bridge.
- Caspers, Lucien D.,Spils, Julian,Damrath, Mattis,Lork, Enno,Nachtsheim, Boris J.
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p. 9161 - 9178
(2020/08/14)
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- IrIII-Catalyzed Selective ortho-Monoiodination of Benzoic Acids with Unbiased C?H Bonds
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An iridium-catalyzed selective ortho-monoiodination of benzoic acids with two equivalent C?H bonds is presented. A wide range of electron-rich and electron-poor substrates undergo the reaction under mild conditions, with >20:1 mono/di selectivity. Importantly, the C?H iodination occurs selectively ortho to the carboxylic acid moiety in substrates bearing competing coordinating directing groups. The reaction is performed at room temperature and no inert atmosphere or exclusion of moisture is required. Mechanistic investigations revealed a substrate-dependent reversible C?H activation/protodemetalation step, a substrate-dependent turnover-limiting step, and the crucial role of the AgI additive in the deactivation of the iodination product towards further reaction.
- Weis, Erik,Johansson, Magnus J.,Martín-Matute, Belén
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supporting information
p. 10185 - 10190
(2020/07/31)
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- Iodolopyrazolium Salts: Synthesis, Derivatizations, and Applications
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The synthesis of iodolopyrazolium triflates via an oxidative cyclization of 3-(2-iodophenyl)-1H-pyrazoles is described. The reaction is characterized by a broad substrate scope, and various applications of these novel cyclic iodolium salts acting as useful synthetic intermediates are demonstrated, in particular in site-selective ring openings. This was finally applied to generate derivatives of the anti-inflammatory drug celecoxib. Their application as highly active halogen-bond donors is shown as well.
- Boelke, Andreas,Caspers, Lucien D.,Kuczmera, Thomas J.,Lork, Enno,Nachtsheim, Boris J.
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supporting information
p. 7261 - 7266
(2020/10/05)
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- Synthesis of novel natural product-like diaryl acetylenes as hypoxia inducible factor-1 inhibitors and antiproliferative agents
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The selaginellin derivatives are a type of novel natural pigments with an unusual alkynyl phenol skeleton from the genus Selaginella. Some of these natural compounds were previously reported to show important bioactivities, including anticancer activity, cardiovascular protection and phosphodiesterase-4 inhibition. We designed and synthesized fifteen biphenyl-containing diaryl acetylene derivatives mimicking the skeleton of natural alkynyl phenols. In MTT assay in cancer cells, compounds 1c, 2d, 2g, 2h, 2i and 2j exhibited potent antiproliferative activity. The evaluation of Hypoxia Inducible Factor-1 (HIF-1) pathway inhibitory activity in dual luciferase assay demonstrated that most tested compounds exhibited moderate to good activities. Compounds 1a, 2f and 2h displayed high HIF-1 inhibitory activities and relatively low cytotoxicity, demonstrating great potential as HIF-1 inhibitors. These results afford a new strategy for the discovery of new HIF-1 inhibitors and anti-proliferative agents from natural or synthetic diaryl acetylene derivatives.
- Wang, Shisheng,Liu, Liqiang,Guo, Xiuhan,Li, Guangzhe,Wang, Xu,Dong, Huijuan,Li, Yueqing,Zhao, Weijie
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p. 13878 - 13886
(2019/05/16)
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- Analogues of acetylene phenolic natural product as well as preparation method and application of analogues
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The invention belongs to the technical field of drugs and chemical engineering, and discloses analogues of an acetylene phenolic natural product as well as a preparation method and application of theanalogues. The analogues of the acetylene phenolic natural product prepared by the invention have remarkable inhibiting effect on a hypoxia-inducible factor HIF-1, and partial chemical compounds showsremarkable anti-proliferation effect to cancer cells; the chemical compounds and pharmaceutically acceptable salts thereof have wide application space in preparing anti-tumor drugs and HIF-1 inhibitors.
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Paragraph 0101-0103
(2019/08/06)
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- Preparation method of key intermediate of anti-hepatitis C drug ledipasvir
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The invention provides a preparation method of a key intermediate 1-(7-bromo-9,9-difluoro-9H-fluoren-2-yl)-2-chloroethanone. The method comprises the steps as follows: 2-amino-5-bromobenzoic acid is taken as a raw material, and subjected to diazotization, iodination,synthesis of 5-bromo-2-iodobenzoic acid, methylation, coupling reaction with phenylboronic acid, ester hydrolysis, acyl chlorination,intramolecular Friedel-Crafts alkylation, carbonyl reduction, iodization, fluorination and final reaction with 2-chloro-N-methoxy-N-methylacetamide to prepare the target product. The process adopts easily available starting raw materials, is low in price and free of hazardous process and has mild reaction conditions..
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Paragraph 0053-0055
(2019/05/08)
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- Reactions of 1-Arylbenziodoxolones with Azide Anion: Experimental and Computational Study of Substituent Effects
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New substituted 1-arylbenziodoxolones were prepared and their reactivity with azide anion as a nucleophile was investigated. It was found that independent of the presence of substituents, all reactions of 1-arylbenziodoxolones proceed as nucleophilic substitution of the iodonium leaving group in the electron-deficient benziodoxolone benzene ring. The presence of bulky substituents in the ortho position of the aryl ring slows the reaction down, while the presence of a moderately electron-withdrawing bromine substituent in para position to the iodine atom in the benziodoxolone ring moderately increases the rate of substitution. The presence of a strongly electron-withdrawing nitro group in the para position to the iodine atom in the benziodoxolone ring dramatically increases the rate of substitution. These observations are in agreement with the electronic requirements for internal nucleophilic substitution in the benziodoxole ring. A quantum-chemical computational study of the possible reaction paths is in agreement with the observed effects of substituents on the reactivity of arylbenziodoxolones in this reaction.
- Yusubov, Mekhman S.,Soldatova, Natalia S.,Postnikov, Pavel S.,Valiev, Rashid R.,Svitich, Dmitry Y.,Yusubova, Roza Y.,Yoshimura, Akira,Wirth, Thomas,Zhdankin, Viktor V.
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p. 640 - 647
(2018/02/14)
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- Copper-catalyzed domino reaction of carbodiimides and benzoic acid derivatives for the synthesis of quinazolinediones
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Quinazolinediones were obtained from 2-iodobenzoic acids and carbodiimide derivatives under mild reaction conditions via a copper-catalyzed domino reaction. The absence of an external base was essential to avoid the generation of amide by-products. Both alkyl- and aryl-substituted carbodiimides gave the corresponding quinazolinediones. However, the use of aryl-substituted carbodiimides resulted in low yields due to an undesired elimination process.
- Duangjan, Chanikan,Rukachaisirikul, Vatcharin,Saithong, Saowanit,Kaeobamrung, Juthanat
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supporting information
p. 3537 - 3540
(2018/08/29)
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- Synthesis of DIBAC analogues with excellent SPAAC rate constants
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In search for increased reactivity in strain-promoted azide alkyne cycloadditions (SPAAC), the synthesis of new and more reactive cyclooctynes is of pivotal importance. To identify cyclooctynes with enhanced reactivity, without loss of stability, the synthesis and kinetic analysis of new dibenzoazacyclooctyne (DIBAC) analogues were conducted. Starting from iodobenzyl alcohol analogues and ortho-ethynylaniline various substituted dihydrodibenzo[b,f]azocines were produced. Subsequent bromination and elimination proved to be difficult depending on the aromatic substitution pattern, yielding chloro-, bromo-, and methoxy-substituted DIBACs in moderate yield. In the elimination reaction towards nitro- and Br,Cl-DIBAC, the corresponding cyclooctene was obtained instead of the cyclooctyne. Additionally, a dimethoxy-substituted DIBAC analogue was prepared following an alternative route involving light-induced deprotection of a cyclopropenone derivative. In total, four DIBAC analogues were successfully prepared showing excellent rate constants in the SPAAC reaction ranging from 0.45 to 0.9 M-1 s -1, which makes them comparable to the fastest cyclooctynes currently known. This journal is the Partner Organisations 2014.
- Debets, Marjoke F.,Prins, Jasper S.,Merkx, Donny,Van Berkel, Sander S.,Van Delft, Floris L.,Van Hest, Jan C. M.,Rutjes, Floris P. J. T.
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supporting information
p. 5031 - 5037
(2014/07/07)
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- Direct carbocyclizations of benzoic acids: Catalyst-controlled synthesis of cyclic ketones and the development of tandem aHH (acyl Heck-Heck) reactions
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The formation of exo-methylene indanones and indenones from simple ortho-allyl benzoic acid derivatives has been developed. Selective formation of the indanone or indenone products in these reactions is controlled by choice of ancillary ligand. This new process has a low environmental footprint as the products are formed in high yields using low catalyst loadings, while the only stoichiometric chemical waste generated from the reactants in the transformation is acetic acid. The conversion of the active cyclization catalyst into the Hermman-Beller palladacycle was exploited in a one-pot tandem acyl Heck-Heck (aHH) reaction, and utilized in the synthesis of donepezil. Carboxylic acids in aHH: Simple ortho-allyl benzoic acid derivatives have been utilized in an acyl Heck (aH) reaction to selectively form indanones and indenones. The conversion of the active cyclization catalyst into the Hermman-Beller palladacycle was exploited in a one-pot tandem acyl Heck-Heck (aHH) reaction to form two sp 2-sp2 bonds of (E)-trisubstituted olefins.
- Miles, Kelsey C.,Le, Chi,Stambuli, James P.
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supporting information
p. 11336 - 11339
(2014/10/16)
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- SUBSTITUTED AZADIBENZOCYCLOOCTYNE COMPOUNDS AND THEIR USE IN METAL-FREE CLICK REACTIONS
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The invention relates to a substituted azadibenzocyclooctyne compound according to Formula (5): The invention also relates to a conjugate wherein a substituted azadibenzocyclooctyne according to the invention is conjugated to a label, and to the use of these conjugates for bioorthogonal labeling, imaging or modification of a target molecule, e.g. surface modification. The invention further relates to a method for the modification of a target molecule, wherein a conjugate according to the invention is reacted with a compound comprising a 1,3-dipole or a 1,3-(hetero)diene.
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Page/Page column 28
(2014/12/12)
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- Palladium-catalyzed insertion of N-tosylhydrazones for the synthesis of isoindolines
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Isoindolines are synthesized by palladium-catalyzed coupling reaction of N-(2-iodobenzyl) anilines with α,β-unsaturated N-tosylhydrazones. The reaction has several potential advantages: (1) toleration of a wide range of functional groups, (2) easy to handle and with mild conditions, (3) enriches the isoindoline family, (4) two new bonds form in one step.
- Zhou, Ping-Xin,Luo, Jian-Yi,Zhao, Lian-Biao,Ye, Yu-Ying,Liang, Yong-Min
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supporting information
p. 3254 - 3256
(2013/05/08)
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- Palladium-catalyzed annulation reactions of methyl o-halobenzoates with azabicyclic alkenes: A general protocol for the construction of benzo[c]phenanthridine derivatives
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The annulation reaction of methyl o-halobenzoates with azabicyclic alkenes proceeds efficiently to give the corresponding benzo[c]phenanthridine derivatives in good to excellent yields using a developed base-free methodology based on our preliminary studies. Thirty-seven application examples validate the compatibility of the present strategy with different groups, particularly with the electron-deficient ones, that are difficult to access using other traditional methods. In addition, annulation reactions with non-symmetric azabicyclic alkenes are achieved in high regioselectivity.
- Guo, Cui,Huang, Kanglun,Wang, Bo,Xie, Longguang,Xu, Xiaohua
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p. 17271 - 17280
(2013/09/24)
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- Copper-catalyzed cross-coupling interrupted by an opportunistic smiles rearrangement: An efficient domino approach to dibenzoxazepinones
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Unexpected Smiles! An unusual and highly regioselective synthesis of dibenzoxazepinones by a domino sequence assisted by an unexpected Smiles rearrangement is reported. The process is effective on electronically differentiated phenols and shows a high tolerance to variation in the benzamide substituents. A plausible path for the reaction, supported by preliminary mechanistic data, is offered. Copyright
- Kitching, Matthew O.,Hurst, Timothy E.,Snieckus, Victor
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p. 2925 - 2929
(2012/05/04)
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- Synthesis of 6-bromo-2-arylindoles using 2-iodobenzoic acid as precursor
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The synthesis of 6-bromo-2-arylindoles starting from readily available 2-iodobenzoic acid is presented. Regioselective bromination of the latter was followed by Curtius rearrangement and trapping of the isocyanate with benzyl alcohol led to the benzyl carbamate of 2-iodo-5-bromoaniline. Chemoselective Sonogashira coupling of this compound with arylacetylenes followed by TBAF induced 5-endo-dig cyclization gave the desired bromo indoles. The method allows selective introduction of a bromine atom at the indole C-6 position.
- Valois-Escamilla, Ismael,Alvarez-Hernandez, Alejandro,Rangel-Ramos, Luis Felipe,Suárez-Castillo, Oscar Rodolfo,Ayala-Mata, Francisco,Zepeda-Vallejo, Gerardo
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supporting information; experimental part
p. 3726 - 3728
(2011/08/06)
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- Sodium [2′-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-4′-(6- ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetate (AM432): A potent, selective prostaglandin D2 receptor antagonist
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Compound 21 (AM432) was identified as a potent and selective antagonist of the DP2 receptor (CRTH2). Modification of a bi-aryl core identified a series of tri-aryl antagonists of which compound 21 proved a viable clinical candidate. AM432 shows excellent potency in a human whole blood eosinophil shape change assay with prolonged incubation, a comparatively long off-rate from the DP2 receptor, excellent pharmacokinetics in dog and in vivo activity in two mouse models of inflammatory disease after oral dosing.
- Stock, Nicholas,Volkots, Deborah,Stebbins, Karin,Broadhead, Alex,Stearns, Brian,Roppe, Jeffrey,Parr, Timothy,Baccei, Christopher,Bain, Gretchen,Chapman, Charles,Correa, Lucia,Darlington, Janice,King, Christopher,Lee, Catherine,Lorrain, Daniel S.,Prodanovich, Pat,Santini, Angelina,Evans, Jilly F.,Hutchinson, John H.,Prasit, Peppi
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scheme or table
p. 1036 - 1040
(2011/03/21)
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- DNA-programmed Glaser-Eglinton reactions for the synthesis of conjugated molecular wires
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Wire self-assembly: Short oligo(phenylene ethynylene) modules (black structures, see picture) are assembled by attached DNA strands, which also direct the formation of 1,3-diyne linkages between the modules by the Cu-mediated Glaser-Eglinton reaction to selectively form dimer, trimer, and tetramer conjugated wires of up to 8 nm in length.
- Ravnsbaek, Jens B.,Jacobsen, Mikkel F.,Rosen, Christian B.,Voigt, Niels V.,Gothelf, Kurt V.
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supporting information; experimental part
p. 10851 - 10854
(2012/01/02)
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- OPE/OPV H-mers: Synthesis, electronic properties, and spectroscopic responses to binding with transition metal ions
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A new type of structurally defined H-shaped OPE/OPV co-oligomers (termed H-mers) functionalized with various donor and/or acceptor end groups was synthesized by iterative Sonogashira coupling and Horner-Wadsworth-Emmons (HWE) reactions. Electronic substitution effects on the H-mer backbone were investigated by UV-vis absorption and fluorescence spectroscopy. Some H-mers were found to show spectral responses upon binding to an acid (TFA) or transition metal ions, revealing the applicability of H-mers in the field of chromophore and fluorophore based chemosensors.
- Zhou, Ningzhang,Wang, Li,Thompson, David W.,Zhao, Yuming
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supporting information; experimental part
p. 125 - 143
(2011/03/17)
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- INHIBITORS OF STEAROYL-COA DESATURASE
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity.
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- H-shaped OPE/OPV oligomers: A new member of 2D-conjugated fluorophore cores
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(Chemical Equation Presented) A new class of two-dimensional (2D), π-conjugated, skewed H-shaped co-oligomers of phenylene vinylene and phenylene ethynylene (11a-d, termed H-mers) were synthesized using Sonogashira coupling and Wittig-Horner reactions as the key steps. Electronic and spectroscopic properties of the H-mers were investigated by UV-vis absorption, fluorescence spectroscopic techniques, and ab initio calculations (HF/3-21G). Two amino-containing functional H-mers (11b and 11d) were found to exhibit appealing fluorescence sensitivity to selected Bronsted acids and transition-metal ions.
- Zhou, Ningzhang,Wang, Li,Thompson, David W.,Zhao, Yuming
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supporting information; experimental part
p. 3001 - 3004
(2009/04/18)
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- Functionalized AB-type monomers for Suzuki polycondensation
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A high yield synthesis of two phenylene and biphenylene derived AB-type monomers for Suzuki polycondensation is described. They carry solubilizing alkyl groups and free and methyl-protected hydroxy functional groups for further modifications.
- Frahn,Schluter
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p. 1301 - 1304
(2007/10/03)
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