22246-17-9Relevant academic research and scientific papers
Site- and Enantioselective C?H Oxygenation Catalyzed by a Chiral Manganese Porphyrin Complex with a Remote Binding Site
Burg, Finn,Gicquel, Maxime,Breitenlechner, Stefan,P?thig, Alexander,Bach, Thorsten
, p. 2953 - 2957 (2018)
A chiral manganese porphyrin complex with a two-point hydrogen-bonding site was prepared and probed in catalytic C?H oxygenation reactions of 3,4-dihydroquinolones. The desired oxygenation occurred with perfect site selectivity at the C4 methylene group and with high enantioselectivity in favor of the respective 4S-configured secondary alcohols (12 examples, 29–97 % conversion, 19–68 % yield, 87–99 % ee). Mechanistic studies support the hypothesis that the reaction proceeds through a rate- and selectivity-determining attack of the reactive manganese oxo complex at the hydrogen-bound substrate and an oxygen transfer by a rebound mechanism.
Dehydrogenative and Redox-Neutral N-Heterocyclization of Aminoalcohols Catalyzed by Manganese Pincer Complexes
Brzozowska, Aleksandra,Rueping, Magnus,Sklyaruk, Jan,Zubar, Viktoriia
, (2022/03/17)
A new manganese catalyzed heterocyclization of aminoalcohols has been accomplished. A wide range of heterocycles were synthesized, including 1,2,3,4-tetrahydroquinolines, dihydroquinolinones, and 2,3,4,5-tetrahydro-1H-benzo[b]azepines. The reaction is performed under mild reaction conditions using air and moisture stable manganese catalysts. The desired heterocycles were obtained in good to excellent yields.
Cu-Catalyzed Phenol O-Methylation with Methylboronic Acid
Bartlett, Mairead E.,Chavez, Angela K.,Gaffney, Uma Bhagwat,Gorin, David J.,Lee, Joyce,Sharew, Betemariam,Wu, Miranda,Zhu, Yingchuan
supporting information, p. 5661 - 5664 (2021/11/11)
A Cu-catalyzed oxidative cross-coupling of phenols with methylboronic acid to form aryl methyl ethers has been developed, expanding the scope of Chan-Evans-Lam alkylation. Electron-deficient phenol derivatives with a broad array of functional groups are methylated in high yields. Increased reaction temperature and catalyst loading enables the methylation of substrates incorporating pyridine and dihydroquinolone motifs. Electron-rich phenol derivatives are poor substrates for the methylation; the characterization of C?H homodimerization products formed from these substrates illuminates a competing mechanistic pathway.
Discovery of tetrahydroquinolines and benzomorpholines as novel potent RORγt agonists
Xia, Yuehan,Yu, Mingcheng,Zhao, Yunpeng,Xia, Li,Huang, Yafei,Sun, Nannan,Song, Meiqi,Guo, Huimin,Zhang, Yunyi,Zhu, Di,Xie, Qiong,Wang, Yonghui
supporting information, (2020/12/04)
The retinoic acid receptor-related orphan receptor γt (RORγt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). RORγt agonists increase basal activity of RORγt and could provide a potential approach to cancer immunotherapy. Herein, hit compound 1 was identified as a weak RORγt agonist during in-house library screening. Changes in LHS core of 1 led to the identification of tetrahydroquinoline compound 6 as a partial RORγt agonist (max. act. = 39.3%). Detailed structure-activity relationship on substituent of the LHS core, amide linker and RHS arylsulfonyl moiety was explored and a novel series of tetrahydroquinolines and benzomorpholines was discovered as potent RORγt agonists. Tetrahydroquinoline compound 8g (EC50 = 8.9 ± 0.4 nM, max. act. = 104.5%) and benzomorpholine compound 9g (EC50 = 7.5 ± 0.6 nM, max. act. = 105.8%) were representative compounds with high RORγt agonistic activity in dual FRET assay, and they showed good activity in cell-based Gal4 reporter gene assay and Th17 cell differentiation assay (104.5% activation at 300 nM of 8g; 59.4% activation at 300 nM of 9g). The binding modes of 8g and 9g as well as the two RORγt inverse agonists accidentally discovered were also discussed.
Selective Fragments for the CREBBP Bromodomain Identified from an Encoded Self-assembly Chemical Library
Catalano, Marco,Moroglu, Mustafa,Balbi, Petra,Mazzieri, Federica,Clayton, James,Andrews, Katrina H.,Bigatti, Martina,Scheuermann, J?rg,Conway, Stuart J.,Neri, Dario
supporting information, p. 1752 - 1756 (2020/08/21)
DNA-encoded chemical libraries (DECLs) are collections of chemical moieties individually coupled to distinctive DNA barcodes. Compounds can be displayed either at the end of a single DNA strand (i. e., single-pharmacophore libraries) or at the extremities of two complementary DNA strands (i. e., dual-pharmacophore libraries). In this work, we describe the use of a dual-pharmacophore encoded self-assembly chemical (ESAC) library for the affinity maturation of a known 4,5-dihydrobenzodiazepinone ring (THBD) acetyl-lysine (KAc) mimic for the cyclic-AMP response element binding protein (CREB) binding protein (CREBBP or CBP) bromodomain. The new pair of fragments discovered from library selection showed a sub-micromolar affinity for the CREBBP bromodomain in fluorescence polarization and ELISA assays, and selectivity against BRD4(1).
One-pot ortho-amination of aryl C-H bonds using consecutive iron and copper catalysis
Henry, Martyn C.,McGrory, Rochelle,Faggyas, Réka J.,Mostafa, Mohamed A. B.,Sutherland, Andrew
, p. 4629 - 4639 (2019/05/17)
A one-pot approach for ortho-coupling of arenes with non-actived N-nucleophiles has been developed using sequential iron and copper catalysis. Regioselective ortho-activation of anisoles, anilines and phenols was achieved through iron(iii) triflimide catalysed iodination, followed by a copper(i)-catalysed, ligand-assisted coupling reaction with N-heterocycle, amide and sulfonamide-based nucleophiles. The synthetic utility of this one-pot, two-step method for the direct amination of ortho-aryl C-H bonds was demonstrated with the late-stage functionalisation of 3,4-dihydroquinolin-2-ones. This allowed the preparation of a TRIM24 bromodomain inhibitor and a series of novel analogues.
Multibond Forming Tandem Reactions of Anilines via Stable Aryl Diazonium Salts: One-Pot Synthesis of 3,4-Dihydroquinolin-2-ones
Faggyas, Réka J.,Grace, Megan,Williams, Lewis,Sutherland, Andrew
, p. 12595 - 12608 (2018/10/15)
A fast and effective one-pot tandem process that generates Heck coupled products from readily available anilines via stable aryl diazonium tosylate salts was developed. The mild and simple procedure involves rapid formation of aryl diazonium salts using a polymer-supported nitrite reagent and p-tosic acid, followed by a base-free Heck-Matsuda coupling with acrylates and styrenes. Using 2-nitroanilines as substrates, the one-pot tandem process was extended for the direct synthesis of 3,4-dihydroquinolin-2-ones. In this case, following diazotization and Heck-Matsuda coupling to give methyl cinnamates, addition of hydrogen and reutilization of the palladium catalyst for reduction of the nitro group and hydrogenation of the alkene resulted in efficient formation of 3,4-dihydroquinolin-2-ones. The synthetic utility of this one-pot, four-stage process was demonstrated with the five-pot synthesis of a quinolinone-based sodium ion channel modulator.
Enabling CO Insertion into o-Nitrostyrenes beyond Reduction for Selective Access to Indolin-2-one and Dihydroquinolin-2-one Derivatives
Yang, Li,Shi, Lijun,Xing, Qi,Huang, Kuo-Wei,Xia, Chungu,Li, Fuwei
, p. 10340 - 10348 (2018/10/20)
The transition metal-catalyzed reductive cyclization of o-nitrostyrene in the presence of carbon monoxide (CO) has been developed to be a general synthetic route to an indole skeleton, wherein CO was used as a reductant to deoxidize nitroarene into nitrosoarene and/or nitrene with CO2 release, but the selective insertion of CO into the heterocyclic product with higher atom economy has not yet been realized. Herein, the Pd-catalyzed reduction of o-nitrostyrene by CO and its regioselective insertion were efficiently achieved to produce synthetically useful five- and six-membered benzo-fused lactams. Detailed investigations revealed that the chemoselectivity to indole or lactam was sensitive to the nature of the counteranions of Pd2+ precursors, whereas ligands significantly decided the carbonylative regioselectivity by different reaction pathways. Using PdCl2/PPh3/B(OH)3 (condition A), an olefin hydrocarboxylation was primarily initiated followed by partial reduction of the NO2 moiety and cyclization reaction to give N-hydroxyl indolin-2-one, which was further catalytically reduced by CO to afford the indolin-2-one as the final product with up to 95% yield. When the reaction was conducted under the Pd(TFA)2/BINAP/TsOH·H2O system (condition B), complete deoxygenation and carbonylation of the NO2 group occurred initially to yield the corresponding isocyanate followed by internal hydrocyclization to generate 3,4-dihydroquinolin-2-one with up to 98% yield. Importantly, the methodology could be efficiently applied in the synthesis of marketed drug Aripiprazole.
A series of potent crebbp bromodomain ligands reveals an induced-fit pocket stabilized by a cation-π interaction
Rooney, Timothy P. C.,Filippakopoulos, Panagis,Fedorov, Oleg,Picaud, Sarah,Cortopassi, Wilian A.,Hay, Duncan A.,Martin, Sarah,Tumber, Anthony,Rogers, Catherine M.,Philpott, Martin,Wang, Minghua,Thompson, Amber L.,Heightman, Tom D.,Pryde, David C.,Cook, Andrew,Paton, Robert S.,Mueller, Susanne,Knapp, Stefan,Brennan, Paul E.,Conway, Stuart J.
supporting information, p. 6126 - 6130 (2014/06/23)
The benzoxazinone and dihydroquinoxalinone fragments were employed as novel acetyl lysine mimics in the development of CREBBP bromodomain ligands. While the benzoxazinone series showed low affinity for the CREBBP bromodomain, expansion of the dihydroquino
Multicomponent multicatalyst reactions (MC)2R: One-pot synthesis of 3,4-dihydroquinolinones
Zhang, Lei,Sonaglia, Lorenzo,Stacey, Jason,Lautens, Mark
, p. 2128 - 2131 (2013/06/05)
A Rh/Pd/Cu catalyst system led to an efficient synthesis of dihydroquinolinones in one-pot, two operations. The reaction features the first triple metal-catalyzed transformations in one reaction vessel, without any intermediate workup. The conjugate-addition/amidation/amidation reaction sequence is highly modular, divergent, and practical.
