1464-98-8Relevant academic research and scientific papers
Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides
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.
, p. 14498 - 14501 (2017)
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.
Gold catalysis: Mild conditions for the synthesis of oxazoles from N-propargylcarboxamides and mechanistic aspects
Hashmi, A. Stephen K.,Weyrauch, Jan P.,Frey, Wolfgang,Bats, Jan W.
, p. 4391 - 4394 (2004)
(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.
Efficient and general synthesis of 5-(alkoxycarbonyl)methylene-3-oxazolines by palladium-catalyzed oxidative carbonylation of prop-2-ynylamides
Bacchi, Alessia,Costa, Mirco,Gabriele, Bartolo,Pelizzi, Giancarlo,Salerno, Giuseppe
, p. 4450 - 4457 (2002)
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.
Synthesis and biological evaluation of azamacrolide comprising the triazole moiety as quorum sensing inhibitors
Zhang, Bin,Guo, Bingyi,Bai, Yunlong,Lu, Huizhe,Dong, Yanhong
, (2018)
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.
Chemical modifications of poly(vinyl chloride) to poly(vinyl azide) and "clicked" triazole bearing groups for application in metal cation extraction
Ouerghui, Abid,Elamari, Hichem,Dardouri, Mokthar,Ncib, Sana,Meganem, Faouzi,Girard, Christian
, p. 191 - 197 (2016)
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'
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
Krasavin, Mikhail,Lukin, Alexei,Vedekhina, Tatiana,Manicheva, Olga,Dogonadze, Marine,Vinogradova, Tatiana,Zabolotnykh, Natalia,Rogacheva, Elizaveta,Kraeva, Liudmila,Yablonsky, Piotr
, p. 1115 - 1126 (2018)
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
Water Can Accelerate Homogeneous Gold Catalysis
Hashmi, A. Stephen K.,Rudolph, Matthias,Stein, Philipp M.
supporting information, p. 4264 - 4271 (2021/08/03)
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
Novel propargylamine-based inhibitors of cholinesterases and monoamine oxidases: Synthesis, biological evaluation and docking study
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
, (2021/09/07)
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.
Synthesis and structure-activity studies of novel anhydrohexitol-based Leucyl-tRNA synthetase inhibitors
De Ruysscher, Dries,Pang, Luping,Lenders, Stijn M.G.,Cappoen, Davie,Cos, Paul,Rozenski, Jef,Strelkov, Sergei V.,Weeks, Stephen D.,Van Aerschot, Arthur
, (2020/12/02)
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.
N-Heterocyclic Iod(az)olium Salts – Potent Halogen-Bond Donors in Organocatalysis
Boelke, Andreas,Kuczmera, Thomas J.,Lork, Enno,Nachtsheim, Boris J.
supporting information, p. 13128 - 13134 (2021/08/09)
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.
