- Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides
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Carboxylic acid reductases (CARs) catalyze the reduction of a broad range of carboxylic acids to aldehydes using the cofactors adenosine triphosphate and nicotinamide adenine dinucleotide phosphate, and have become attractive biocatalysts for organic synthesis. Mechanistic understanding of CARs was used to expand reaction scope, generating biocatalysts for amide bond formation from carboxylic acid and amine. CARs demonstrated amidation activity for various acids and amines. Optimization of reaction conditions, with respect to pH and temperature, allowed for the synthesis of the anticonvulsant ilepcimide with up to 96 % conversion. Mechanistic studies using site-directed mutagenesis suggest that, following initial enzymatic adenylation of substrates, amidation of the carboxylic acid proceeds by direct reaction of the acyl adenylate with amine nucleophiles.
- Wood, Alexander J. L.,Weise, Nicholas J.,Frampton, Joseph D.,Dunstan, Mark S.,Hollas, Michael A.,Derrington, Sasha R.,Lloyd, Richard C.,Quaglia, Daniela,Parmeggiani, Fabio,Leys, David,Turner, Nicholas J.,Flitsch, Sabine L.
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- Gold catalysis: Mild conditions for the synthesis of oxazoles from N-propargylcarboxamides and mechanistic aspects
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(Chemical Equation Presented) 2,5-Disubstituted oxazoles are synthesized from the corresponding propargylcarboxamides under mild reaction conditions via homogeneous catalysis by AuCl3. While monitoring the conversion via 1H NMR spectroscopy, an intermediate 5-methylene-4,5-dihydrooxazole can be observed and accumulated up to 95%, being the first direct and catalytic preparative access to such alkylidene oxazolines. The intermediate was fully characterized and can be trapped at -25°C for several weeks. Deuteration experiments show a stereospecific mode of the two first steps of the reaction.
- Hashmi, A. Stephen K.,Weyrauch, Jan P.,Frey, Wolfgang,Bats, Jan W.
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- Efficient and general synthesis of 5-(alkoxycarbonyl)methylene-3-oxazolines by palladium-catalyzed oxidative carbonylation of prop-2-ynylamides
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A variety of prop-2-ynylamides have been carbonylated under oxidative conditions to give oxazolines, oxazolines with chelating groups, and bisoxazolines bearing an (alkoxycarbonyl)methylene chain at the 5 position in good yields. The cyclization-alkoxycarbonylation process was carried out in alcoholic media at 50-70°C and under 24 bar pressure of 3:1 carbon monoxide/air in the presence of catalytic amounts of 10% Pd/C or PdI2 in conjunction with KI. Cyclization occurred by anti attack of an oxygen function on the palladium-coordinated triple bond, followed by stereospecific alkoxycarbonylation, strictly resulting in E-stereochemistry. The structures of representative oxazolines and bisoxazolines have been determined by X-ray diffraction analysis.
- Bacchi, Alessia,Costa, Mirco,Gabriele, Bartolo,Pelizzi, Giancarlo,Salerno, Giuseppe
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- Synthesis and biological evaluation of azamacrolide comprising the triazole moiety as quorum sensing inhibitors
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Novel azamacrolides comprising the triazole moiety were synthesized and evaluated for their quorum sensing inhibitor activities on the Agrobacterium tumefaciens. It was found that the inhibition rate of compound Z12-3 at 200 mg/L (0.45 mM) can reach 67%. The potential binding modes between these molecules and the TraR QS receptor was performed by molecular docking. The results showed that the two nitrogen atoms in the triazole ring of Z12-3 formed hydrogen bonds with GLN-2, and the carbonyl group (C=O) in the amide formed hydrogen bonds with water. It was worth noting that the carbonyl group on the macrolides formed hydrogen bonds with the G-106 base in the DNA. These azamacrolides may block quorum sensing expression through key amino acid residues or DNA bases in the TraR QS receptor by hydrogen-bonded.
- Zhang, Bin,Guo, Bingyi,Bai, Yunlong,Lu, Huizhe,Dong, Yanhong
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- Chemical modifications of poly(vinyl chloride) to poly(vinyl azide) and "clicked" triazole bearing groups for application in metal cation extraction
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Chemical modification of poly(vinyl chloride) (PVC) by the replacement of chlorine atom presents a considerable interest in this work. In the first phase, PVC was partially azided with a sodium azide. Click-chemistry based on Copper (I)-catalyzed Huisgen'
- Ouerghui, Abid,Elamari, Hichem,Dardouri, Mokthar,Ncib, Sana,Meganem, Faouzi,Girard, Christian
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- Conjugation of a 5-nitrofuran-2-oyl moiety to aminoalkylimidazoles produces non-toxic nitrofurans that are efficacious in vitro and in vivo against multidrug-resistant Mycobacterium tuberculosis
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Within the general nitrofuran carboxamide chemotype, chimera derivatives incorporating diversely substituted imidazoles attached via an alkylamino linker were synthesized. Antimycobacterial evaluation against drug-sensitive M. tuberculosis H37Rv strain id
- Krasavin, Mikhail,Lukin, Alexei,Vedekhina, Tatiana,Manicheva, Olga,Dogonadze, Marine,Vinogradova, Tatiana,Zabolotnykh, Natalia,Rogacheva, Elizaveta,Kraeva, Liudmila,Yablonsky, Piotr
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- Water Can Accelerate Homogeneous Gold Catalysis
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A selection of gold-catalyzed reactions was examined in a kinetic study on the influence of water on the rate constant. Two intramolecular reactions and one intermolecular reaction, which proceed via proton transfer and/or protodeauration steps, were inve
- Hashmi, A. Stephen K.,Rudolph, Matthias,Stein, Philipp M.
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supporting information
p. 4264 - 4271
(2021/08/03)
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- Novel propargylamine-based inhibitors of cholinesterases and monoamine oxidases: Synthesis, biological evaluation and docking study
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A combination of several pharmacophores in one molecule has been successfully used for multi-target-directed ligands (MTDL) design. New propargylamine substituted derivatives combined with salicylic and cinnamic scaffolds were designed and synthesized as potential cholinesterases and monoamine oxidases (MAOs) inhibitors. They were evaluated in vitro for inhibition of acetyl- (AChE) and butyrylcholinesterase (BuChE) using Ellman's method. All the compounds act as dual inhibitors. Most of the derivatives are stronger inhibitors of AChE, the best activity showed 5-bromo-N-(prop-2-yn-1-yl)salicylamide 1e (IC50 = 8.05 μM). Carbamates (4-bromo-2-[(prop-2-yn-1-yl)carbamoyl]phenyl ethyl(methyl)carbamate 2d and 2,4-dibromo-6-[(prop-2-yn-1-yl)carbamoyl]phenyl ethyl(methyl)carbamate 2e were selective and the most active for BuChE (25.10 and 26.09 μM). 4-Bromo-2-[(prop-2-yn-1-ylimino)methyl]phenol 4a was the most potent inhibitor of MAOs (IC50 of 3.95 and ≈10 μM for MAO-B and MAO-A, respectively) along with a balanced inhibition of both cholinesterases being a real MTDL. The mechanism of action was proposed, and binding modes of the hits were studied by molecular docking on human enzymes. Some of the derivatives also exhibited antioxidant properties. In silico prediction of physicochemical parameters affirm that the molecules would be active after oral administration and able to reach brain tissue.
- Krátky, Martin,Vu, Quynh Anh,?těpánková, ?árka,Maruca, Annalisa,Silva, Tiago Barros,Ambro?, Martin,Pflégr, Václav,Rocca, Roberta,Svr?ková, Katarína,Alcaro, Stefano,Borges, Fernanda,Vin?ová, Jarmila
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- Synthesis and structure-activity studies of novel anhydrohexitol-based Leucyl-tRNA synthetase inhibitors
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Leucyl-tRNA synthetase (LeuRS) is a clinically validated target for the development of antimicrobials. This enzyme catalyzes the formation of charged tRNALeu molecules, an essential substrate for protein translation. In the first step of catalysis LeuRS activates leucine using ATP, forming a leucyl-adenylate intermediate. Bi-substrate inhibitors that mimic this chemically labile phosphoanhydride-linked nucleoside have proven to be potent inhibitors of different members of the aminoacyl-tRNA synthetase family but, to date, they have demonstrated poor antibacterial activity. We synthesized a small series of 1,5-anhydrohexitol-based analogues coupled to a variety of triazoles and performed detailed structure-activity relationship studies with bacterial LeuRS. In an in vitro assay, Kiapp values in the nanomolar range were demonstrated. Inhibitory activity differences between the compounds revealed that the polarity and size of the triazole substituents affect binding. X-ray crystallographic studies of N. gonorrhoeae LeuRS in complex with all the inhibitors highlighted the crucial interactions defining their relative enzyme inhibitory activities. We further examined their in vitro antimicrobial properties by screening against several bacterial and yeast strains. While only weak antibacterial activity against M. tuberculosis was detected, the extensive structural data which were obtained could make these LeuRS inhibitors a suitable starting point towards further antibiotic development.
- De Ruysscher, Dries,Pang, Luping,Lenders, Stijn M.G.,Cappoen, Davie,Cos, Paul,Rozenski, Jef,Strelkov, Sergei V.,Weeks, Stephen D.,Van Aerschot, Arthur
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- N-Heterocyclic Iod(az)olium Salts – Potent Halogen-Bond Donors in Organocatalysis
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This article describes the application of N-heterocyclic iod(az)olium salts (NHISs) as highly reactive organocatalysts. A variety of mono- and dicationic NHISs are described and utilized as potent XB-donors in halogen-bond catalysis. They were benchmarked in seven diverse test reactions in which the activation of carbon- and metal-chloride bonds as well as carbonyl and nitro groups was achieved. N-methylated dicationic NHISs rendered the highest reactivity in all investigated catalytic applications with reactivities even higher than all previously described monodentate XB-donors based on iodine(I) and (III) and the strong Lewis acid BF3.
- Boelke, Andreas,Kuczmera, Thomas J.,Lork, Enno,Nachtsheim, Boris J.
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supporting information
p. 13128 - 13134
(2021/08/09)
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- Silver-Free Au(I) Catalysis Enabled by Bifunctional Urea- and Squaramide-Phosphine Ligands via H-Bonding
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A library of gold(I) chloride complexes with phosphine ligands incorporating pendant (thio)urea and squaramide H-bond donors was prepared with the aim of promoting chloride abstraction from Au(I) via H-bonding. In the absence of silver additives, complexes bearing squaramides and trifluoromethylated aromatic ureas displayed good catalytic activity in the cyclization of N-propargyl benzamides, as well as in a 1,6-enyne cycloisomerization, a tandem cyclization-indole addition reaction and the hydrohydrazination of phenylacetylene. Kinetic studies and DFT calculations indicate that the energetic span of the reaction is accounted by both the chloride abstraction step, facilitated by the bidentate H-bond donor via an associative mechanism, and the subsequent cyclization step.
- Echavarren, Antonio M.,Franchino, Allegra,Martí, àlex,Nejrotti, Stefano
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supporting information
p. 11989 - 11996
(2021/07/06)
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- Rh(iii)-Catalyzed three-component cascade annulation to produce theN-oxopropyl chain of isoquinolone derivatives
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Developing powerful methods to introduce versatile functional groups at theN-substituents of isoquinolone scaffolds is still a great challenge. Herein, we report a novel three-component cascade annulation reaction to efficiently construct theN-oxopropyl chain of isoquinolone derivativesviarhodium(iii)-catalyzed C-H activation/cyclization/nucleophilic attack, with oxazoles used both as the directing group and potential functionalized reagents.
- He, Yuan,Liao, Xian-Zhang,Dong, Lin,Chen, Fen-Er
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supporting information
p. 561 - 567
(2021/02/06)
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- Fluorocyclization of Allyl Alcohols and Amines to Access 3-Functionalized Oxetanes and Azetidines
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An efficient method to prepare 3-functionalized oxetanes and azetidines has been realized by fluorocyclization of readily available 2-azidoallyl/2-alkoxyallyl alcohols and amines. Notably, this is the first example applying the fluorocyclization strategy to construct four-membered heterocycles. The pendant electron-donating group (-N3 or -OR) plays a crucial role in polarizing the C= C double bond and facilitating the cyclization process, as verified by DFT and experimental studies.
- Cao, Shanshan,Li, Linxuan,Liu, Zhaohong,Ning, Yongquan,Wu, Yong,Zanoni, Giuseppe,Zhang, Qi,Zhang, Xinyu
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supporting information
p. 3674 - 3679
(2021/05/31)
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- Practical one-pot amidation of N -Alloc-, N -Boc-, and N -Cbz protected amines under mild conditions
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A facile one-pot synthesis of amides from N-Alloc-, N-Boc-, and N-Cbz-protected amines has been described. The reactions involve the use of isocyanate intermediates, which are generated in situ in the presence of 2-chloropyridine and trifluoromethanesulfonyl anhydride, to react with Grignard reagents to produce the corresponding amides. Using this reaction protocol, a variety of N-Alloc-, N-Boc-, and N-Cbz-protected aliphatic amines and aryl amines were efficiently converted to amides with high yields. This method is highly effective for the synthesis of amides and offers a promising approach for facile amidation.
- Hong, Wan Pyo,Tran, Van Hieu,Kim, Hee-Kwon
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p. 15890 - 15895
(2021/05/19)
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- Metal-Free Selective Modification of Secondary Amides: Application in Late-Stage Diversification of Peptides
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Here we solve a long-standing challenge of the site-selective modification of secondary amides and present a simple two-step, metal-free approach to selectively modify a particular secondary amide in molecules containing multiple primary and secondary amides. Density functional theory (DFT) provides insight into the activation of C-N bonds. This study encompasses distinct chemical advances for late-stage modification of peptides thus harnessing the amides for the incorporation of various functional groups into natural and synthetic molecules.
- Adebomi, Victor,Sriram, Mahesh,Streety, Xavier,Raj, Monika
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p. 6189 - 6193
(2021/08/01)
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- Method for preparing amide from carboxylic acid under irradiation of blue light by taking iridium and cobalt complexes as catalysts
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The invention relates to a method for preparing amide from carboxylic acid under the irradiation of blue light by taking iridium and cobalt complexes as catalysts, and belongs to the field of chemistry. The method comprises the following step of: by taking R substituted carboxylic acid and R1' and R2' substituted amines as raw materials, triphenylphosphine as a deoxidizing agent, [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 as a photocatalyst and Co(dmgH)(dmgH2)Cl2 as a metal complex catalyst, reacting in dichloromethane in an inert atmosphere and under the irradiation of blue light to obtain an amide compound, wherein R is an aryl group, a heteroaryl group, a protected amino group, a substituted alkyl group, a substituted aryl group or a substituted protected amino group, R1' is a hydrogen group, a substituted alkyl group, a phenyl group or a substituted phenyl group, and R2' is a hydrogen group, a substituted alkyl group, a phenyl group or a substituted phenyl group.
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Paragraph 0099-0100
(2021/05/12)
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- New ursolic acid derivatives bearing 1,2,3-triazole moieties: design, synthesis and anti-inflammatory activity in vitro and in vivo
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Abstract: In order to discover novel anti-inflammatory agents, three series of compounds obtained by appending 1,2,3-triazole moieties on ursolic acid were designed and synthesized. All compounds have been screened for their anti-inflammatory activity by using an ear edema model. The potent anti-inflammatory compound was subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assays. In general, the derivatives were found to be potent anti-inflammatory activity. Especially, the compound 11b exhibited the strongest activity of all of the compounds prepared, with 82.81% inhibition after intraperitoneal administration, which was better than celecoxib as a positive control. Molecular docking results unclose the rationale for the interaction of the compound 11b with COX-2 enzyme. Further studies revealed that compound 11b exhibited effective COX-2 inhibitory activity, with half-maximal inhibitor concentration (IC50) value of 1.16?μM and selectivity index (SI = 64.66) value close to that of celecoxib (IC50 = 0.93?μM, SI = 65.47). Taken together, these results could suggest a promising chemotype for development of new COX-2-targeting anti-inflammatory agent. Graphic abstract: [Figure not available: see fulltext.]
- Bai, Xue-Qian,Cao, Li-Ting,Li, Chun-Shi,Sun, Si-Mei,Zhang, Tian-Yi,Zhao, Dong-Hai
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- COMPOUNDS FOR USE IN THE TREATMENT OF LIVER DISEASE
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Bile acid derivatives, methods of manufacture thereof, and uses thereof are disclosed herein. The bile acid derivatives have demonstrated potential as therapeutics for treating liver disease.
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Paragraph 00129-00130 00133
(2021/02/26)
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- Carboxylic Acid Deoxyfluorination and One-Pot Amide Bond Formation Using Pentafluoropyridine (PFP)
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This work describes the application of pentafluoropyridine (PFP), a cheap commercially available reagent, in the deoxyfluorination of carboxylic acids to acyl fluorides. The acyl fluorides can be formed from a range of acids under mild conditions. We also demonstrate that PFP can be utilized in a one-pot amide bond formation via in situ generation of acyl fluorides. This one-pot deoxyfluorination amide bond-forming reaction gives ready access to amides in yields of ≤94%.
- Brittain, William D. G.,Cobb, Steven L.
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p. 5793 - 5798
(2021/08/01)
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- The bioisosteric modification of pyrazinamide derivatives led to potent antitubercular agents: Synthesis via click approach and molecular docking of pyrazine-1,2,3-triazoles
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Tuberculosis remains as a major public health risk which causes the highest mortality rate globally and an improved regimen is required to treat the drug-resistant strains. Pyrazinamide is a first-line antitubercular drug used in combination therapy with other anti-TB drugs. Herein, we describe the modification of pyrazinamide structure using bioisosterism and rational approaches by incorporating the 1,2,3-triazole moiety. Three sets of pyrazine-1,2,3-triazoles (3a-o, 5a-o and 9a-l) are designed, synthesized and evaluated for their in vitro inhibitory potency against mycobacterium tuberculosis H37Rv. The pyrazine-1,2,3-triazoles synthesized through the bioisosteric modification displayed improved activity as compared to rationally modified pyrazine-1,2,3-triazoles. Among 42 title compounds, seven derivatives demonstrated significant anti-tubercular activity with the MIC of 1.56 μg/mL, which are two-fold more potent than the parent compound pyrazinamide. Further, the synthesized pyrazinamide analogs demonstrated moderate inhibition activity against several bacterial strains and possessed an acceptable in vitro cytotoxicity profile as well. Additionally, the activity profile of pyrazine-1,2,3-triazoles was validated by performing the molecular docking studies against the Inh A enzyme. Furthermore, in silico ADME prediction revealed good oral bioavailability for the potent molecules.
- Reddyrajula, Rajkumar,Dalimba, Udayakumar
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- Dual H-bond activation of NHC-Au(i)-Cl complexes with amide functionalized side-arms assisted by H-bond donor substrates or acid additives
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Novel approach with amide-tethered H-bond donor NHC ligands enabled Au(i)-catalysis via H-bonding. The plain NHC-Au(i)-Cl complex catalysed conversions of terminal N-propynamides to oxazolines, and enyne cycloisomerization with an acid additive, in DCM at
- Sepp?nen, Otto,Aikonen, Santeri,Muuronen, Mikko,Alamillo-Ferrer, Carla,Burés, Jordi,Helaja, Juho
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supporting information
p. 14697 - 14700
(2020/12/02)
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- BTK Inhibitors and uses thereof
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The invention discloses a bruton's tyrosine kinase (BTK) inhibitor and use thereof. Specifically, the invention provides heteroaromatic compounds or stereoisomers, geometrical isomers, tautomers, racemates, nitrogen oxides, hydrates, solvates, metabolites and pharmaceutically acceptable salts or prodrugs thereof, and pharmaceutical compositions containing the heteroaromatic compounds; the invention also discloses use of the heteroaromatic compounds or the pharmaceutical compositions containing the heteroaromatic compounds in preparation of medicines; the medicines can be used for treating autoimmune diseases, inflammatory diseases or proliferative diseases.
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Paragraph 1248-1253
(2020/05/02)
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- InCl3-catalyzed 5- exo-dig cyclization/1,6-conjugate addition of N -propargylamides with p -QMs to construct oxazole derivatives
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An InCl3-catalyzed atom-economic intramolecular 5-exo-dig cyclization/1,6-conjugate addition/aromatization of N-propargylamides with p-QMs to produce oxazoles tethering diarylmethane has been successfully developed. InCl3 not only se
- Li, Ming,Li, Xue,Nan, Guang-Ming,Wen, Li-Rong,Yan, Ting-Xun,Yao, Tian-Yu
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supporting information
p. 1780 - 1784
(2020/03/17)
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- Synthesis of 2,2,2-Trifluoroethyl Oxazoles, Oxazolines and Furans via Alkyne Oxytrifluoromethylation
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This study reports an oxytrifluoromethylation method for construction of oxazoles and furans motif and the concurrent incorporation of a 2,2,2-trifluoroethyl group at the aromatic C5-position. High-valent copper(III) trifluoromethyl compounds are crucial
- Dong, Jia-Jia,Zhang, Song-Lin
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supporting information
p. 795 - 800
(2020/01/24)
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- Structure-activity relationships for binding of 4-substituted triazole-phenols to macrophage migration inhibitory factor (MIF)
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Macrophage migration inhibitory factor (MIF) is a versatile protein that plays a role in inflammation, autoimmune diseases and cancers. Development of novel inhibitors will enable further exploration of MIF as a drug target. In this study, we investigated structure-activity relationships of MIF inhibitors using a MIF tautomerase activity assay to measure binding. Importantly, we notified that transition metals such as copper (II) and zinc (II) interfere with the MIF tautomerase activity under the assay conditions applied. EDTA was added to the assay buffer to avoid interference of residual heavy metals with tautomerase activity measurements. Using these assay conditions the structure-activity relationships for MIF binding of a series of triazole-phenols was explored. The most potent inhibitors in this series provided activities in the low micromolar range. Enzyme kinetic analysis indicates competitive binding that proved reversible. Binding to the enzyme was confirmed using a microscale thermophoresis (MST) assay. Molecular modelling was used to rationalize the observed structure-activity relationships. The most potent inhibitor 2d inhibited proliferation of A549 cells in a clonogenic assay. In addition, 2d attenuated MIF induced ERK phosphorylation in A549 cells. Altogether, this study provides insights in the structure-activity relationships for MIF binding of triazole-phenols and further validates this class of compounds as MIF binding agents in cell-based studies.
- Chen, Deng,Dekker, Frank J.,Fokkens, Marieke,Kok, Tjie,Poelarends, Gerrit J.,Proietti, Giordano,Xiao, Zhangping,van Merkerk, Ronald
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- Fluorocyclization of N-Propargylamides to Oxazoles by Electrochemically Generated ArIF2
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A sustainable synthesis of 5-fluoromethyl-2-oxazoles by use of electrochemistry has been demonstrated. Hypervalent ArIF2 is generated by direct electrochemical oxidation of iodoarene ArI in Et3N·5HF and mediates the fluorocyclization
- Berger, Michael,Herszman, John D.,Waldvogel, Siegfried R.
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supporting information
(2019/10/08)
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- Zn(OTf)2-catalyzed, microwave-promoted synthesis of 2-substituted 5-methyloxazoles from propargylic amides
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The versatile conversion of propargylic amides to the respective 2-substituted 5-methyloxazoles was efficiently catalyzed by Zn(OTf)2 (5 mol%) under microwave irradiation in toluene. The method was applicable to a wide range of aliphatic, aroma
- Safrygin, Alexander,Dar'in, Dmitry,Lukin, Alexei,Bakholdina, Anna,Sapegin, Alexander,Krasavin, Mikhail
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supporting information
p. 777 - 779
(2019/02/13)
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- Assessing the influence of phosphine substituents on the catalytic properties of self-stabilised digold(i) complexes with supporting ferrocene phosphinonitrile ligands
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Gold(i) phosphine complexes are often used in catalysis, but the role of their auxiliary ligands still remains poorly understood. Thus, building on our previous research, we prepared a series of Au(i) complexes [Au2(μ-R2PfcCN)2][SbF6]2 (fc = ferrocene-1,1
- Barta, Ondrej,Cisarova, Ivana,Schulz, Jiri,Stepnicka, Petr
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supporting information
p. 11258 - 11262
(2019/07/31)
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- An Improved Synthesis of Urea Derivatives from N -Acylbenzotriazole via Curtius Rearrangement
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The good leaving tendency of the benzotriazole moiety has been exploited for the synthesis of symmetric, unsymmetric, N -acyl, and cyclic ureas in good yields from N -acylbenzotriazoles by treating the latter with various amines in the presence of TMSN 3 /Et 3 N in a sealed tube. The salient features of the devised protocol includes the high-yield, mild, metal-free, one-pot reaction conditions, and short reaction time. Furthermore, in many cases, no column chromatography is required for the purification.
- Agrahari, Anand K.,Singh, Anoop S.,Singh, Sumit K.,Tiwari, Vinod K.,Yadav, Mangal S.
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p. 3443 - 3450
(2019/09/07)
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- Catalyst-Free, Metal-Free, and Chemoselective Transamidation of Activated Secondary Amides
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A simple protocol, which is catalyst-free, metal-free, and chemoselective, for transamidation of activated secondary amides in ethanol as solvent under mild conditions is reported. A wide range of amines, amino acids, amino alcohols, and the substituents, which are problematic in catalyzed transamidation, are tolerated in this methodology. The transamidation reaction was successfully extended to water as the medium as well. The present methodology appears to be better than the other catalyzed transamidations reported recently.
- Ramkumar, Rajagopal,Chandrasekaran, Srinivasan
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p. 921 - 932
(2019/02/10)
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- Clickable coupling of carboxylic acids and amines at room temperature mediated by SO2F2: A significant breakthrough for the construction of amides and peptide linkages
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The construction of amide bonds and peptide linkages is one of the most fundamental transformations in all life processes and organic synthesis. The synthesis of structurally ubiquitous amide motifs is essential in the assembly of numerous important molecules such as peptides, proteins, alkaloids, pharmaceutical agents, polymers, ligands and agrochemicals. A method of SO2F2-mediated direct clickable coupling of carboxylic acids with amines was developed for the synthesis of a broad scope of amides in a simple, mild, highly efficient, robust and practical manner (>110 examples, >90% yields in most cases). The direct click reactions of acids and amines on a gram scale are also demonstrated using an extremely easy work-up and purification process of washing with 1 M aqueous HCl to provide the desired amides in greater than 99% purity and excellent yields.
- Wang, Shi-Meng,Zhao, Chuang,Zhang, Xu,Qin, Hua-Li
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p. 4087 - 4101
(2019/04/30)
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- Glycosyl triazoles as novel insect β-N-acetylhexosaminidase OfHex1 inhibitors: Design, synthesis, molecular docking and MD simulations
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The insect enzyme GH20 β-N-acetyl-D-hexosaminidase OfHex1 represents an important chitinolytic enzyme found in the agricultural pest Ostrinia furnacalis (Guenée) and inhibition of this enzyme has been considered a promising strategy for the development of eco-friendly pesticides. In this article, based on the structure of the catalytic domains of OfHex1, a series of novel glycosyl triazoles were designed and synthesized via Cu-catalyzed azide-alkyne [3+2] cycloaddition reaction. To investigate the potency and selectivity of these glycosyl triazoles, the inhibition activities towards OfHex1 and HsHexB (human β-N-acetylhexosaminidase B) were studied. Particularly compound 17c (OfHex1, Ki = 28.68 μM; HsHexB, Ki > 100 μM) exhibited a suitable activity and selectivity against OfHex1. Furthermore, the possible inhibitory mechanisms of 17c with OfHex1 were studied using molecular docking and MD simulations. The structure-activity relationship results as well as the formed binding patterns may provide promising insights into the further development of novel OfHex1 inhibitors.
- Dong, Lili,Shen, Shengqiang,Chen, Wei,Lu, Huizhe,Xu, Dongdong,Jin, Shuhui,Yang, Qing,Zhang, Jianjun
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p. 2315 - 2322
(2018/12/11)
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- An Industrial Perspective on Counter Anions in Gold Catalysis: Underestimated with Respect to “Ligand Effects”
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The conversion of a variety of well-known test reactions, representing the key reactivity patterns of gold catalysis, were analyzed by GC and 1H NMR. The study is focused on establishing of a strategical approach for the consideration of ligand
- Schie?l, Jasmin,Schulmeister, Jürgen,Doppiu, Angelino,W?rner, Eileen,Rudolph, Matthias,Karch, Ralf,Hashmi, A. Stephen K.
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supporting information
p. 2493 - 2502
(2018/04/25)
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- An Industrial Perspective on Counter Anions in Gold Catalysis: On Alternative Counter Anions
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A comparison of versatile counter anions was investigated by means of a variety of well-known test reactions representing the key reactivity patterns of homogeneous gold catalysis, the catalytic activity was monitored by GC and 1H NMR. As previ
- Schie?l, Jasmin,Schulmeister, Jürgen,Doppiu, Angelino,W?rner, Eileen,Rudolph, Matthias,Karch, Ralf,Hashmi, A. Stephen K.
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supporting information
p. 3949 - 3959
(2018/09/06)
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- Photoreduction of Thioether Gold(III) Complexes: Mechanistic Insight and Homogeneous Catalysis
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Complexes formed between AuCl3 and thioether ligands underwent a photoinduced reductive elimination under homogeneous conditions in dichloromethane and toluene solutions to afford the corresponding AuI complexes. All the gold(III) complexes were rapidly reduced to the gold(I) chloride complexes under 365 nm irradiation or ambient light while being thermally stable below 55 °C. The mechanism of photoreduction through Cl2 elimination is discussed based on a kinetic study and the chemical trapping of chlorine species: Cl2, radical Cl., and possibly Cl+. The catalytic activities of the gold(III) chloride complexes and the corresponding gold(I) complexes obtained by in situ reduction were evaluated in the cyclization of N-propargylic amides to oxazoles. The merits of such photoreducible complexes in homogeneous gold catalysis are illustrated by a cascade reaction catalyzed by thioether gold complexes that affords a 4H-quinolizin-4-one in high yields.
- Cao, Zhen,Bassani, Dario M.,Bibal, Brigitte
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supporting information
p. 18779 - 18787
(2018/11/23)
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- Sequential Au/Cu Catalysis: A Two Catalyst One-Pot Protocol for the Enantioselective Synthesis of Oxazole α-Hydroxy Esters via Intramolecular Cyclization/Intermolecular Alder-Ene Reaction
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A convenient protocol for the enantioselective synthesis of oxazole α-hydroxy ester derivatives 4 from readily available propargylamides 1 and alkylglyoxylates 3 was developed. The first step of the one-pot procedure is the selective intramolecular in situ formation of an alkylideneoxazoline 2, which then in an intermolecular reaction is enantioselectively transformed to the oxazole α-hydroxy ester derivatives 4 in quantitative yield and good to excellent enantioselectivity via an asymmetric copper(II)-catalyzed Alder-ene reaction. (Figure presented.).
- Nalivela, Kumara Swamy,Rudolph, Matthias,Baeissa, Elham S.,Alhogbi, Basma G.,Mkhalid, Ibraheem A. I.,Hashmi, A. Stephen K.
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supporting information
p. 2183 - 2190
(2018/04/30)
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- Palladium-Catalyzed Cascade Difluoroalkylation/Cyclization of N-Propargylamides: Synthesis of Oxazoles and Oxazolines
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A palladium-catalyzed process to construct oxazoles and oxazolines with broad functional-group tolerance has been developed, and the method introduces difluoromethyl groups into heterocycles in a one-pot fashion. This system uses a carbonyl oxygen as the acceptor for the addition of a vinylpalladium intermediate to achieve the cyclization. Oxazoline derivatives are generated as the Z-isomer with high stereoselectivity. Additionally, we validated the tentative mechanism of this reaction.
- Ma, Jun-Wei,Wang, Qiang,Wang, Xin-Gang,Liang, Yong-Min
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p. 13296 - 13307
(2018/11/02)
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- Base-Promoted Cycloisomerization for the Synthesis of Oxazoles and Imidazoles
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Treatment of propargylamides or propargylamidines with cesium carbonate in DMSO results in the formation of the corresponding oxazoles or imidazoles in good yields. A large variety of substrates with various functional groups are tolerated. DFT study on a model substrate reveals that the reactions proceed via a sequence involving allene formation, intramolecular cyclization, and double-bond isomerization.
- Zhang, Lidan,Xiao, Ke,Qiao, Yan,Li, Xin,Song, Chuanjun,Chang, Junbiao
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supporting information
p. 6913 - 6918
(2018/12/05)
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- Synthesis of gibberellic acid derivatives and their effects on plant growth
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A series of novel C-3-OH substituted gibberellin derivatives bearing an amide group were designed and synthesized from the natural product gibberellic acid (GA3). Their activities on the plant growth regulation of rice and Arabidopsis were evaluated in vivo. Among these compounds, 10d and 10f exhibited appreciable inhibitory activities on rice (48.6% at 100 μmol/L) and Arabidopsis (41.4% at 100mol/L), respectively. These results provide new insights into the design and synthesis of potential plant growth regulators.
- Tian, Hao,Xu, Yiren,Liu, Shaojin,Jin, Dingsha,Zhang, Jianjun,Duan, Liusheng,Tan, Weiming
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supporting information
(2017/06/08)
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- 1,2,3-triazole-ring-containing amide compounds, and preparation method and application thereof
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The invention belongs to the technical field of agricultural chemistry, and particularly relates to 1,2,3-triazole-ring-containing amide compounds, and a preparation method and application thereof. The preparation method comprises the following steps: carrying out reaction on R-group carboxylic acid and alkynyl propylamine to obtain terminal-group alkyne compounds; reducing 4'-chloro-2-nitrobiphenyl to obtain 4'-chloro-2-aminobiphenyl, carrying out reaction on the 4'-chloro-2-aminobiphenyl and chloracetyl chloride, and carrying out reaction on the obtained compound and sodium azide to obtain azides; and carrying out click reaction on the terminal-group alkyne compounds and azides to obtain the 1,2,3-triazole-ring-containing amide compounds (CAU-BC). The method has the advantages of cheap required raw materials and simple reaction route. The CAU-BC has certain bactericidal activities for gray mold of tomato, Pythium aphanidermatum, cercospora brown spot of peanut, potato blight, seedling blight of cotton and sclerotinia rot of rape, and has favorable bactericidal activities for rice blast; and the bactericidal activities of most of the compounds for rice blast reach 80% or above.
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Paragraph 0041; 0042
(2017/08/28)
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- Iron-catalyzed C-H/N-H activation by triazole guidance: Versatile alkyne annulation
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Iron-catalyzed C-H/N-H functionalizations were achieved by the aid of modular triazole amides. The alkyne annulation allowed for the expedient synthesis of valuable isoquinolone scaffolds with high levels of chemo-, site- and regio-selectivities.
- Cera,Haven,Ackermann
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supporting information
p. 6460 - 6463
(2017/07/10)
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- Base-controlled highly selective synthesis of alkyl 1,2-bis(boronates) or 1,1,2-tris(boronates) from terminal alkynes
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Transition-metal-free base-controlled highly regioselective synthesis of alkyl 1,2-bis(boronates) or 1,1,2-tris(boronates) from various terminal alkynes has been disclosed. These reactions are efficient, practical and mild with good regioselectivity, exce
- Gao, Guoliang,Yan, Jianxiang,Yang, Kai,Chen, Fener,Song, Qiuling
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supporting information
p. 3997 - 4001
(2017/09/07)
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- Merging gold catalysis, organocatalytic oxidation, and Lewis acid catalysis for chemodivergent synthesis of functionalized oxazoles from: N -propargylamides
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Novel catalytic systems consisting of cationic gold complexes, N-hydroxyphthalimide (NHPI), and transition-metal-based Lewis acids have been developed for the one-pot synthesis of functionalized oxazoles from N-propargylamides with excellent functional group tolerance. These transformations demonstrated the excellent compatibility of homogeneous gold catalysis with organocatalytic oxidative carbon-nitrogen bond formations using tert-butyl nitrite as the terminal oxidant. Moreover, oxazolecarbonitriles or carboxamides can be easily synthesized in a one-pot protocol according to the different synthetic requirements.
- Mai, Shaoyu,Rao, Changqing,Chen, Ming,Su, Jihu,Du, Jiangfeng,Song, Qiuling
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supporting information
p. 10366 - 10369
(2017/09/25)
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- Direct, efficient NHC-catalysed aldehyde oxidative amidation:: In situ formed benzils as unconventional acylating agents
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A new N-heterocyclic carbene-catalysed oxidative amidation of aldehydes has been developed which converts the aldehyde to a benzil acylating agent in situ. The process uses an air-recyclable oxidant and a nucleophilic co-catalyst and does not require the use of a large excess of either one coupling partner or catalyst.
- Kumar, Vikas,Connon, Stephen J.
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supporting information
p. 10212 - 10215
(2017/09/22)
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- An Unconventional Reaction of 2,2-Diazido Acylacetates with Amines
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We have discovered that 2,2-diazido acylacetates, a class of compounds with essentially unknown reactivity, can be coupled to amines through a new strategy that does not involve any reagents. 2,2-Diazido acetate is the unconventional leaving group under carbon–carbon bond cleavage. This reaction leads to the construction of amide bonds, tolerates various functionalities and is performed equally well in numerous solvents under experimentally simple conditions. We also demonstrate that the isolation of the 2,2-diazido acylacetate compounds can be circumvented: Acylacetates were easily fragmented when treated with (Bu4N)N3 and iodine in the presence of an amine at room temperature. By using this method, a broad range of acylacetates with various structural motifs were directly transformed into amides.
- H?ring, Andreas P.,Biallas, Phillip,Kirsch, Stefan F.
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supporting information
p. 1526 - 1539
(2017/04/01)
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- Palladium(II)-Catalyzed Directed anti-Hydrochlorination of Unactivated Alkynes with HCl
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A regioselective anti-hydrochlorination of unactivated alkynes is reported. The reaction utilizes in situ generated HCl as the source of both the Cl- and H+ and is catalyzed by palladium(II) acetate, with loadings as low as 25 ppm. Removable picolinamide and 8-aminoquinoline bidentate directing groups are used to control the regioselectivity of the chloropalladation step and stabilize the resulting alkenylpalladium(II) intermediate for subsequent protodepalladation. This method provides access to a broad array of substituted alkenyl chlorides in excellent yields and with high regioselectivity. The products from this transformation were successfully derivatized via Stille coupling to a variety of trisubstituted alkene products. Reaction progress kinetic analysis was performed, shedding light on a possible mechanism for this catalytic process.
- Derosa, Joseph,Cantu, Annabelle L.,Boulous, Mark N.,O'Duill, Miriam L.,Turnbull, Joshua L.,Liu, Zhen,De La Torre, Daizy M.,Engle, Keary M.
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supporting information
p. 5183 - 5193
(2017/05/04)
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- Unique physicochemical and catalytic properties dictated by the B3NO2 ring system
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The expansion of molecular diversity beyond what nature can produce is a fundamental objective in chemical sciences. Despite the rich chemistry of boron-containing heterocycles, the 1,3-dioxa-5-aza-2,4,6-triborinane (DATB) ring system, which is characterized by a six-membered B3NO2 core, remains elusive. Here, we report the synthesis of m-terphenyl-templated DATB derivatives, displaying high stability and peculiar Lewis acidity arising from the three suitably arranged boron atoms. We identify a particular utility for DATB in the dehydrative amidation of carboxylic acids and amines, a reaction of high academic and industrial importance. The three boron sites are proposed to engage in substrate assembly, lowering the entropic cost of the transition state, in contrast with the operative mechanism of previously reported catalysts and amide coupling reagents. The distinct mechanistic pathway dictated by the DATB core will advance not only such amidations, but also other reactions driven by multisite activation.
- Noda, Hidetoshi,Furutachi, Makoto,Asada, Yasuko,Shibasaki, Masakatsu,Kumagai, Naoya
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p. 571 - 577
(2017/06/01)
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- Sulfur–Fluoride Exchange (SuFEx)-Mediated Synthesis of Sterically Hindered and Electron-Deficient Secondary and Tertiary Amides via Acyl Fluoride Intermediates
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Amide bond formation is one of the most executed reactions in chemistry and biology. This is largely due to the ubiquity of the amide functional group in biological molecules, natural products and pharmaceutically important drugs. We report here the development of “SuFExAmide”: a new sulfur–fluoride exchange (SuFEx) click chemistry based protocol for the efficient amidation of carboxylic acids via acyl fluoride intermediates. We have developed benzene-1,3-disulfonyl fluoride as a cost effective, powerful and versatile coupling agent, which delivers challenging secondary and tertiary amides in excellent yields from sterically hindered and electron-deficient amines. The straightforward method offers significant benefits over existing protocols in terms of substrate scope, efficiency and ease of operation and is demonstrated by the synthesis of 44 amides, including GNF6702, an antiprotozoal drug candidate. In the majority of cases, the amide products are obtained in high yield without the need for excess reagents or chromatographic purification.
- Smedley, Christopher J.,Barrow, Andrew S.,Spiteri, Christian,Giel, Marie-Claire,Sharma, Pallavi,Moses, John E.
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p. 9990 - 9995
(2017/08/01)
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- Pyrrolylmethyl functionalized o-carborane derivatives
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The reactions of the 16e half-sandwich complex CpCoS2C2B10H10 (1), diazo esters, and various 1,6-diynes (3a-i; PhN(CH2C CH)2, 4-Me-PhN(CH2C CH)2, 4-OMe-PhN(CH2C CH)2, 4-F-PhN(CH2C CH)2, BzN(CH2C CH)2, O(CH2C CH)2, C(Ac)2(CH2C CH)2, N(CH2C CH)3, NH(CH2C CH)N(CH2C CH)2) were investigated, in which two novel types of B-H activated products CpCoS2B10H9(CH2CO2Et)C5H3N(R)(CHCHCO2Et) (4a-c; R = Ph, 4-Me-Ph, 4-OMe-Ph) and the key intermediate CpCoS2B10H9(CHCO2Me) (CH2CO2Me) (9) were isolated. 9 features a reactive Co-B bond, which triggers insertion of various 1,6-diynes to further lead to different final products. Substrates 3a-c are activated by the Co-B bond to produce o-carborane derivatives 4a-c which are functionalized by a cobalt-complexed 3-pyrrolylmethyl group. The pyrrole ring is formed by in situ ring closure of 1,6-diynes. Control experiments and isolation of the intermediate CpCoS2B10H9(CHCO2Me)(CH2CO2Me)HCC CH2N(4-Me-Ph)(CH2C CH) (10) support the proposed mechanism concerning the formation of 4a-c analogues by oxidation. All of the new complexes were characterized by NMR, IR, elemental analysis, and mass spectrometry. The structures of 4a-6a and 9 were determined by single-crystal X-ray diffraction analysis as well.
- Dai, Huimin,Liu, Guifeng,Zhang, Xiaolei,Yan, Hong,Lu, Changsheng
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supporting information
p. 1488 - 1496
(2016/06/09)
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- Design, synthesis, biological evaluation and molecular docking of amide and sulfamide derivatives as Escherichia coli pyruvate dehydrogenase complex E1 inhibitors
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In this study, a series of novel amide derivatives and sulfamide derivatives as potential E. coli PDHc E1 inhibitors were designed and synthesized by optimizing the linker between triazole and benzene ring moieties based on the structure of lead compound
- He, Haifeng,Feng, Jiangtao,He, Junbo,Xia, Qin,Ren, Yanliang,Wang, Fang,Peng, Hao,He, Hongwu,Feng, Lingling
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p. 4310 - 4320
(2016/01/29)
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- A General and Selective Rhodium-Catalyzed Reduction of Amides, N-Acyl Amino Esters, and Dipeptides Using Phenylsilane
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This article describes a selective reduction of functionalized amides, including N-acyl amino esters and dipeptides, to the corresponding amines using simple [Rh(acac)(cod)]. The catalyst shows excellent chemoselectivity in the presence of different sensitive functional moieties. A selective reduction of functionalized amides, including N-acyl amino esters and dipeptides, to the corresponding amines using simple [Rh(acac)(cod)] is described (see scheme). The catalyst shows excellent chemoselectivity in the presence of different sensitive functional moieties. Even the selective reduction of a secondary amide bond in the presence of a ketone is possible.
- Das, Shoubhik,Li, Yuehui,Lu, Liang-Qiu,Junge, Kathrin,Beller, Matthias
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supporting information
p. 7050 - 7053
(2016/05/19)
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- FeBr3-Catalyzed Tandem Reaction of N -Propargylamides with Disulfides or Diselenides for the Synthesis of Oxazole Derivatives
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A methodology of FeBr3-catalyzed tandem reaction of N-propargylamides with disulfides or diselenides for the formation of oxazole derivatives has been developed. The strategy includes several steps in one pot. Series of N-propargylamides and disulfides were suitable as substrates in this transformation for synthesizing the corresponding oxazole derivatives in moderate to good yields.
- Gao, Xu-Hong,Qian, Peng-Cheng,Zhang, Xing-Guo,Deng, Chen-Liang
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supporting information
p. 1110 - 1115
(2016/05/19)
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