6836-19-7Relevant articles and documents
Copper-Catalyzed Methoxylation of Aryl Bromides with 9-BBN-OMe
Li, Chen,Song, Zhi-Qiang,Wang, Dong-Hui,Wang, Jing-Ru
supporting information, p. 8450 - 8454 (2021/11/17)
A Cu-catalyzed cross-coupling reaction between aryl bromides and 9-BBN-OMe to provide aryl methyl ethers under mild conditions is reported. The oxalamide ligand BHMPO plays a key role in the transformation. Various functional groups on bromobenzenes are well tolerated, providing the desired anisole products in moderate to high yields.
Identification of First-in-Class Inhibitors of Kallikrein-Related Peptidase 6 That Promote Oligodendrocyte Differentiation
A?t Amiri, Sabrina,Deboux, Cyrille,Soualmia, Feryel,Chaaya, Nancy,Louet, Maxime,Duplus, Eric,Betuing, Sandrine,Nait Oumesmar, Brahim,Masurier, Nicolas,El Amri, Chahrazade
, p. 5667 - 5688 (2021/05/29)
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) that causes severe motor, sensory, and cognitive impairments. Kallikrein-related peptidase (KLK)6 is the most abundant serine protease secreted in the CNS, mainly by oligodendrocytes, the myelin-producing cells of the CNS, and KLK6 is assumed to be a robust biomarker of MS, since it is highly increased in the cerebrospinal fluid (CSF) of MS patients. Here, we report the design and biological evaluation of KLK6's low-molecular-weight inhibitors, para-aminobenzyl derivatives. Interestingly, selected hit compounds were selective of the KLK6 proteolytic network encompassing KLK1 and plasmin that also participate in the development of MS physiopathology. Moreover, hits were found noncytotoxic on primary cultures of murine neurons and oligodendrocyte precursor cells (OPCs). Among them, two compounds (32 and 42) were shown to promote the differentiation of OPCs into mature oligodendrocytes in vitro constituting thus emerging leads for the development of regenerative therapies.
Selective electrochemical oxidation of aromatic hydrocarbons and preparation of mono/multi-carbonyl compounds
Li, Zhibin,Zhang, Yan,Li, Kuiliang,Zhou, Zhenghong,Zha, Zhenggen,Wang, Zhiyong
, p. 2134 - 2141 (2021/09/29)
A selective electrochemical oxidation was developed under mild condition. Various mono-carbonyl and multi-carbonyl compounds can be prepared from different aromatic hydrocarbons with moderate to excellent yield and selectivity by virtue of this electrochemical oxidation. The produced carbonyl compounds can be further transformed into α-ketoamides, homoallylic alcohols and oximes in a one-pot reaction. In particular, a series of α-ketoamides were prepared in a one-pot continuous electrolysis. Mechanistic studies showed that 2,2,2-trifluoroethan-1-ol (TFE) can interact with catalyst species and generate the corresponding hydrogen-bonding complex to enhance the electrochemical oxidation performance. [Figure not available: see fulltext.]
Aryl or heteroaryl methoxylation reaction method
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Paragraph 0141-0147, (2021/11/21)
The invention discloses an aryl or heteroaryl methoxylation reaction method. The method comprises the following steps: preparing a substrate. The coupling agent, ligand, solvent, catalyst and base are mixed homogeneously in an inert gas to give the aryl or heteroaryl methoxy compounds. Compared with a methoxylation reaction method in the prior art, the method has the advantages that the reaction system conditions are mild, the usage amount of the catalyst and the ligand is low to 5% of the amount of the substrate material, and the catalytic efficiency is improved. The method has better compatibility to different substrate expansion and discovery of aryl halides or heteroaryl halides with different functional groups. The yield of aryl or heteroaryl methoxy compounds prepared by the method disclosed by the invention is 36% - 89%.
Regioselective Electrochemical Cyclobutanol Ring Expansion to 1-Tetralones
Petti, Alessia,Natho, Philipp,Lam, Kevin,Parsons, Philip J.
supporting information, p. 854 - 858 (2021/01/12)
A mild electrochemical method for the regioselective preparation of 1-tetralones under environmentally friendly conditions from readily available cyclobutanols was developed. A series of aromatic- and heteroaromatic-fused 1-tetralones was accessed through ring expansion of the functionalized cyclobutanols via electrochemical generation of alkoxy radicals and intramolecular cyclization.
Potential anti-neuroinflammatory NF-кB inhibitors based on 3,4-dihydronaphthalen-1(2H)-one derivatives
Sun, Yue,Zhou, Yan-Qiu,Liu, Yin-Kai,Zhang, Hong-Qin,Hou, Gui-Ge,Meng, Qing-Guo,Hou, Yun
, p. 1631 - 1640 (2020/08/19)
Nuclear factor kappa B (NF-кB) inhibition represents a new therapeutic strategy for the treatment of neuroinflammatory diseases. In this study, a series of 3,4-dihydronaphthalen-1(2H)-one (DHN; 6a-n, 7a-c) derivatives were synthesised and characterised by NMR and HRMS. We assessed the toxicity and anti-neuroinflammatory properties of these compounds and found that 6m showed the greatest anti-neuroinflammatory properties, with relatively low toxicity. Specifically, 6m significantly reduced reactive oxygen species production, down-regulated the expression of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 and prevented lipopolysaccharide-stimulated BV2 microglia cells polarisation towards an M1 phenotype. Furthermore, 6m significantly decreased IκBα and NF-кB p65 phosphorylation, thus inhibiting the NF-кB signalling pathway. This suggests that 6m may be explored as a functional anti-neuroinflammatory agent for the treatment of inflammatory diseases in the central nervous system, such as multiple sclerosis, traumatic brain injury, stroke and spinal cord injury.
Green synthesis method of medical intermediate benzocyclohexanone compound
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Paragraph 0038-0040, (2020/12/30)
The invention provides a green synthesis method of a benzocyclohexanone compound, and belongs to the technical field of organic synthesis. The method provided by the invention comprises the followingsteps: by taking 4-phenylbutyric acid as a raw material, firstly carrying out reflux reaction with oxalyl chloride in dichloromethane, carrying out vacuum evaporation to dryness to obtain a crude product of the 4-phenylbutyryl chloride compound, then dissolving the crude product in a solvent, adding a metal-doped modified molecular sieve catalyst to start reaction, and stirring the solution at different temperatures to carry out ring closing reaction, thereby obtaining the product; and after the reaction is finished, carrying out suction filtration, solvent washing, column chromatography purification and other operations to obtain the target product benzocyclohexanone compound. The synthesis method disclosed by the invention is environment-friendly in reaction and simple and convenient tooperate, the catalyst can be recycled, and the synthesis method is suitable for green synthesis of the benzocyclohexanone compound.
Green Organic Solvent-Free Oxidation of Alkylarenes with tert-Butyl Hydroperoxide Catalyzed by Water-Soluble Copper Complex
Ajjou, Abdelaziz Nait,Rahman, Ateeq
, p. 165 - 174 (2020/04/15)
Different benzylic compounds were efficiently oxidized to the corresponding ketones with aqueous 70% tert-butyl hydroperoxide (TBHP) and the catalytic system composed of CuCl2.2H2O and 2,2'-biquinoline-4,4'-dicarboxylic acid dipotassium salt (BQC). The catalytic system CuCl2/BQC/TBHP allows obtaining high yields at room temperature under organic solvent-free conditions. The interest of this system lies in its cost effectiveness and its benign nature towards the environment. Benzylic tertbutylperoxy ethers and benzylic alcohols were observed and suggested as the reaction intermediates. Analysis of organic products by atomic absorption did not show any contamination with copper metal. In terms of efficiency, CuCl2/BQC system is comparable or superior to the most of the catalytic systems described in the literature and which are based on toxic organic solvent.
PROCESS FOR THE PREPARATION OF AGOMELATINE IN CRYSTALLINE FORM
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, (2019/05/02)
The present invention pertains to a process for the preparation of polymorph form X of agomelatine, which comprises providing agomelatine, and crystallizing agomelatine in the presence of at least one of an acid and a salt thereof, and to a polymorph form of agomelatine.
Synthesis, crystal structures and anti-inflammatory activity of fluorine-substituted 1,4,5,6-Tetrahydrobenzo[ h]quinazolin-2-Amine derivatives
Sun, Yue,Gao, Zhongfei,Wang, Chunhua,Hou, Guige
, p. 1157 - 1165 (2019/08/13)
Two fluorine-substituted 1,4,5,6-Tetrahydrobenzo[h]quinazolin-2-Amine (BQA) derivatives, namely 2-Amino-4-(2-fluorophenyl)-9-methoxy-1,4,5,6-Tetrahydrobenzo[ h]quinazolin-3-ium chloride, (8), and 2-Amino-4-(4-fluorophenyl)-9-methoxy-1,4,5,6-Tetrahydrobenzo[h]quinazolin-3-ium chloride, (9), both C19H19-FN3O+-Cl-, were generated by Michael addition reactions between guanidine hydrochloride and the -,unsaturated ketones (E)-2-(2-fluorobenzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, C18H15FO2, (6), and (E)-2-(4-fluorobenzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, (7). Because both sides of -,unsaturated ketones (6) or (7) can be attacked by guanidine, we obtained a pair of isomers in (8) and (9). Single-crystal X-ray diffraction indicates that each isomer has a chiral C atom and both (8) and (9) crystallize in the achiral space group P21/c. The chloride ion, as a hydrogen-bond acceptor, plays an important role in the formation of multiple hydrogen bonds. Thus, adjacent molecules are connected through intermolecular hydrogen bonds to generate a banded structure. Furthermore, these bands are linked into an interesting 3D network via hydrogen bonds and - interactions. Fortunately, the solubilities of (8) and (9) were distinctly improved and can exceed 50 mg ml-1 in water or PBS buffer system (pH 7.4) at room temperature. In addition, the results of an investigation of anti-inflammatory activity show that (8) and (9), with o-and p-fluoro substituents, respectively, display more potential for inhibitory effects on LPS-induced NO secretion than starting ketones (6) and (7).
