7550-03-0Relevant articles and documents
Exploiting Cofactor Versatility to Convert a FAD-Dependent Baeyer–Villiger Monooxygenase into a Ketoreductase
Xu, Jian,Peng, Yongzhen,Wang, Zhiguo,Hu, Yujing,Fan, Jiajie,Zheng, He,Lin, Xianfu,Wu, Qi
supporting information, p. 14499 - 14503 (2019/09/17)
Cyclohexanone monooxygenases (CHMOs) show very high catalytic specificity for natural Baeyer–Villiger (BV) reactions and promiscuous reduction reactions have not been reported to date. Wild-type CHMO from Acinetobacter sp. NCIMB 9871 was found to possess an innate, promiscuous ability to reduce an aromatic α-keto ester, but with poor yield and stereoselectivity. Structure-guided, site-directed mutagenesis drastically improved the catalytic carbonyl-reduction activity (yield up to 99 %) and stereoselectivity (ee up to 99 %), thereby converting this CHMO into a ketoreductase, which can reduce a range of differently substituted aromatic α-keto esters. The improved, promiscuous reduction activity of the mutant enzyme in comparison to the wild-type enzyme results from a decrease in the distance between the carbonyl moiety of the substrate and the hydrogen atom on N5 of the reduced flavin adenine dinucleotide (FAD) cofactor, as confirmed using docking and molecular dynamics simulations.
Boron-Catalyzed O-H Bond Insertion of α-Aryl α-Diazoesters in Water
San, Htet Htet,Wang, Shi-Jun,Jiang, Min,Tang, Xiang-Ying
, p. 4672 - 4676 (2018/08/09)
A catalytic, metal-free O-H bond insertion of α-diazoesters in water in the presence of B(C6F5)3·nH2O (2 mol %) was developed, affording a series of α-hydroxyesters in good to excellent yields. The reaction features easy operation and wide substrate scope, and importantly, no metal is needed as compared with the conventional methods. Significantly, this approach further expands the applications of B(C6F5)3 under water-tolerant conditions.
Discovery of novel 2-(3-phenylpiperazin-1-yl)-pyrimidin-4-ones as glycogen synthase kinase-3β inhibitors
Usui, Yoshihiro,Uehara, Fumiaki,Hiki, Shinsuke,Watanabe, Kazutoshi,Tanaka, Hiroshi,Shouda, Aya,Yokoshima, Satoshi,Aritomo, Keiichi,Adachi, Takashi,Fukunaga, Kenji,Sunada, Shinji,Nabeno, Mika,Saito, Ken-Ichi,Eguchi, Jun-ichi,Yamagami, Keiji,Asano, Shouichi,Tanaka, Shinji,Yuki, Satoshi,Yoshii, Narihiko,Fujimura, Masatake,Horikawa, Takashi
, p. 3726 - 3732 (2017/07/27)
We herein describe the results of further evolution of glycogen synthase kinase (GSK)-3β inhibitors from our promising compounds containing a 2-phenylmorpholine moiety. Transformation of the morpholine moiety into a piperazine moiety resulted in potent GSK-3β inhibitors. SAR studies focused on the phenyl moiety revealed that a 4-fluoro-2-methoxy group afforded potent inhibitory activity toward GSK-3β. Based on docking studies, new hydrogen bonding between the nitrogen atom of the piperazine moiety and the oxygen atom of the main chain of Gln185 has been indicated, which may contribute to increased activity compared with that of the corresponding phenylmorpholine analogues. Effect of the stereochemistry of the phenylpiperazine moiety is also discussed.
Asymmetric catalytic arylation of ethyl glyoxylate using organoboron reagents and Rh(i)-phosphane and phosphane-phosphite catalysts
Marques, Carolina Silva,Dindaroglu, Mehmet,Schmalz, Hans-Guenther,Burke, Anthony J.
, p. 6035 - 6041 (2014/01/23)
Herein we report the first application of Rh(i)-phosphane and phosphane-phosphite catalysts in the enantioselective catalytic arylation of ethyl glyoxylate with organoboron reagents, providing access to ethyl mandelate derivatives in high yield (up to 99%) and moderate to very good enantioselectivities (up to 75% ee). Commercial phosphane ligands, such as (R)-MonoPhos and (R)-Phanephos were tested, as well as non-commercial (R,R)-TADDOL-derived phosphane-phosphite ligands. Those ligands containing bulky substituents in the ortho-and para-positions of the chiral phosphite moiety were found to be the most selective.
Azastilbenes: A cut-off to p38 MAPK inhibitors
Poon, Jia-Fei,Alao, John Patrick,Sunnerhagen, Per,Dinér, Peter
, p. 4526 - 4536 (2013/08/23)
Inhibitors with vicinal 4-fluorophenyl/4-pyridine rings on a five- or six-membered heterocyclic ring are known to inhibit the p38 mitogen-activated protein kinase (MAPK), which is a potential target for rheumatoid arthritis and several different types of cancer. Several substituted azastilbene-based compounds with vicinal 4-fluorophenyl/4-pyridine rings were designed using computational docking, synthesized, and evaluated in a cell-free radiometric p38α assay. The biochemical evaluation shows that the best inhibition (down to 110 nM) is achieved for azastilbene-based compounds having an isopropylamine substituent in the 2-position of the pyridine ring. The inhibition of p38 signaling in human breast cancer cells was observed for two of the compounds. The Royal Society of Chemistry 2013.
Iron-catalyzed hydrogenation for the in situ regeneration of an NAD(P)H model: Biomimetic reduction of α-Keto-/α-iminoesters
Lu, Liang-Qiu,Li, Yuehui,Junge, Kathrin,Beller, Matthias
supporting information, p. 8382 - 8386 (2013/09/02)
Two irons for a smoother finish: An NAD(P)H model was regenerated readily in situ by iron-catalyzed reduction with molecular hydrogen. The subsequent biomimetic reduction of α-keto-/ α-iminoesters proceeded smoothly in the presence of an iron-based Lewis acid (LA) to provide α-hydroxyesters and amino acid esters in good to excellent yields (see scheme; NAD(P) +=nicotinamide adenine dinucleotide (phosphate), TM=transition metal). Copyright
COMPOUNDS FOR THE REDUCTION OF β-AMYLOID PRODUCTION
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Page/Page column 97, (2012/08/08)
The present disclosure provides a series of compounds of the formula (I), which modulate β-amyloid peptide (β-ΑΡ) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by β-amyloid peptide (β-ΑΡ) production.
Expeditious and novel synthesis of α-hydroxyesters via rhodium-NHC catalyzed arylation of ethyl glyoxalate
Marques, Carolina S.,Burke, Anthony J.
experimental part, p. 7211 - 7216 (2012/09/05)
The rhodium-NHC catalyzed arylation reaction of ethyl glyoxalate with aryl and alkyl boronic acids provides an efficient method for the synthesis of α-hydroxyesters. A wide range of α-hydroxyesters (up to 12) were prepared in good to excellent yields. KOtBu was the base of choice, along with tert-amyl alcohol as the solvent. As far as we are aware, this is the first report of this catalytic arylation, using rhodium-NHC catalysts with this specific substrate type.
COMPOUNDS FOR THE REDUCTION OF β-AMYLOID PRODUCTION
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Page/Page column 112, (2011/02/24)
The present disclosure provides a series of compounds of the formula (I) which modulate β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by β-amyloid peptide (β-AP) production.
Suzuki-Miyaura coupling reaction of boronic acids and ethyl glyoxylate: Synthetic access to mandelate derivatives
Francesco, Irene Notar,Wagner, Alain,Colobert, Francoise
supporting information; experimental part, p. 5692 - 5695 (2009/05/31)
The palladium-catalyzed coupling reaction of arylboronic acids with ethyl glyoxylate provides a straightforward method for the synthesis of mandelic esters. Pd2(dba)3·CHCl3 in combination with 2-di-tert-butylphosphanylbiphenyl as the catalytic system and Cs 2CO3 as the base were used. The reaction tolerates a wide range of functionalized boronic acids. Mandelic esters were isolated in good-to-excellent yields with a variety of neutral, slightly electron-rich, and slightly electron-poor substituents. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
