22161-86-0Relevant articles and documents
Reshaping the active pocket of esterase Est816 for resolution of economically important racemates
Fan, Xinjiong,Fu, Yao,Liu, Xiaolong,Zhao, Meng
, p. 6126 - 6133 (2021/09/28)
Bacterial esterases are potential biocatalysts for the production of optically pure compounds. However, the substrate promiscuity and chiral selectivity of esterases usually have a negative correlation, which limits their commercial value. Herein, an efficient and versatile esterase (Est816) was identified as a promising catalyst for the hydrolysis of a wide range of economically important substrates with low enantioselectivity. We rationally designed several variants with up to 11-fold increased catalytic efficiency towards ethyl 2-arylpropionates, mostly retaining the initial substrate scope and enantioselectivity. These variants provided a dramatic increase in efficiency for biocatalytic applications. Based on the best variant Est816-M1, several variants with higher or inverted enantioselectivity were designed through careful analysis of the structural information and molecular docking. Two stereoselectively complementary mutants, Est816-M3 and Est816-M4, successfully overcame and even reversed the low enantioselectivity, and several 2-arylpropionic acid derivatives with highEvalues were obtained. Our results offer potential industrial biocatalysts for the preparation of structurally diverse chiral carboxylic acids and further lay the foundation for improving the catalytic efficiency and enantioselectivity of esterases.
Cobalt-Catalyzed Deprotection of Allyl Carboxylic Esters Induced by Hydrogen Atom Transfer
Li, Nan,Gui, Yizhen,Chu, Mengqi,You, Mengdi,Qiu, Xiaohan,Liu, Hejia,Wang, Shiang,Deng, Meng,Ji, Baoming
supporting information, p. 8460 - 8464 (2021/11/13)
A brief, efficient method has been developed for the removal of the allyl protecting group from allyl carboxylic esters using a Co(II)/TBHP/(Me2SiH)2O catalytic system. This facile strategy displays excellent chemoselectivity, functional group tolerance, and high yields. This transformation probably occurs through the hydrogen atom transfer process, and a Co(III)-six-membered cyclic intermediate is recommended.
Palladium-Catalyzed Asymmetric Markovnikov Hydroxycarbonylation and Hydroalkoxycarbonylation of Vinyl Arenes: Synthesis of 2-Arylpropanoic Acids
Guan, Zheng-Hui,Ren, Zhi-Hui,Wang, Yuan,Yang, Hui-Yi,Yao, Ya-Hong,Zou, Xian-Jin
supporting information, p. 23117 - 23122 (2021/09/18)
Asymmetric hydroxycarbonylation is one of the most fundamental yet challenging methods for the synthesis of carboxylic acids. Herein, we reported the development of a palladium-catalyzed highly enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water. A monodentate phosphoramidite ligand L6 plays vital role in the reaction. The reaction tolerates a range of functional groups, and provides a facile and atom-economical approach to an array of 2-arylpropanoic acids including several commonly used non-steroidal anti-inflammatory drugs. The catalytic system has also enabled an asymmetric Markovnikov hydroalkoxycarbonylation of vinyl arenes with alcohols to afford 2-arylpropanates. Mechanistic investigations suggested that the hydropalladation is irreversible and is the regio- and enantiodetermining step, while hydrolysis/alcoholysis is probably the rate-limiting step.
C3 The symmetry contains a chiral ligand H3L of an amide bond. Preparation method and application
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Paragraph 0067; 0111-0114, (2021/09/08)
The invention discloses C. 3 Chiral ligand H with symmetric amide bond3 L Relates to the technical field of material chemistry and chiral chemistry. The invention further provides the chiral ligand H. 3 L Preparation method and application thereof. The present invention has the advantage that the chiral ligand H of the present invention is a chiral ligand. 3 The L has a higher C. 3 The symmetric and flexible amide group enables coordination of the lanthanide metal ions with high coordination number and high oxygen affinity to be assembled into a novel structure-structure lanthanide metal chiral porous coordination cage. Moreover, the abundant chiral amide groups and amino acid residues on the ligand framework can be directly introduced into the synthesized lanthanide metal chiral porous coordination cage, thereby being beneficial to generating multiple chiral recognition sites and unique chiral microenvironments which mimic the biological enzyme binding pocket and further realize the purpose of high enantioselectivity separation of a series of chiral small molecule compounds.
Homochiral Dodecanuclear Lanthanide "cage in Cage" for Enantioselective Separation
Zhu, Chengfeng,Tang, Haitong,Yang, Keke,Fang, Yu,Wang, Kun-Yu,Xiao, Zhifeng,Wu, Xiang,Li, Yougui,Powell, Joshua A.,Zhou, Hong-Cai
supporting information, p. 12560 - 12566 (2021/08/23)
It is extremely difficult to anticipate the structure and the stereochemistry of a complex, particularly when the ligand is flexible and the metal node adopts diverse coordination numbers. When trivalent lanthanides (LnIII) and enantiopure amino acid ligands are utilized as building blocks, self-assembly sometimes yields rare chiral polynuclear structures. In this study, an enantiopure carboxyl-functionalized amino acid-based ligand with C3 symmetry reacts with lanthanum cations to give a homochiral porous coordination cage, (Δ/λ)12-PCC-57. The dodecanuclear lanthanide cage has an unprecedented octahedral "cage-in-cage"framework. During the self-assembly, the chirality is transferred from the enantiopure ligand and fixed by the binuclear lanthanide cluster to give 12 metal centers that have either Δor λ homochiral stereochemistry. The cage exhibits excellent enantioselective separation of racemic alcohols, 2,3-dihydroquinazolinones, and multiple commercially available drugs. This finding exhibits a rare example of a multinuclear lanthanide complex with a dual-walled topology and homochirality. The highly ordered self-assembly and self-sorting of flexible amino acids and lanthanides shed light on the chiral transformation between different complicated artificial systems that mimic natural enzymes.
Ketoprofen intermediate as well as preparation method and application thereof
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, (2020/03/12)
The invention relates to the field, of medicine synthesis, in particular to a ketoprofen intermediate and a preparation method and application. thereof to prepare the ketoprofen, reaction formula by sequentially performing an oxidation reaction, substitution reaction, deamination, deamination and an acidic hydrolysis reaction after formation of the isoxazole compound, by a Diels,Alder reaction with a phenylacetic acid by. a Diels :Alder reaction of a phenylacetic acid. In-flight, X2 or. Ortho or para, R to nitro or amino group1 - COCONR4 R5 , COX1 , COOR2 Or - CNCNCNR2 , R3 , R4 , R5 , R6 The same or different is H or C. 1 - C6 Alkyl, X1 , X2 The same or different is F, Cl, Br or I.
Preparation method of aryl propionic acid compound
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Page/Page column 0121-0125, (2020/10/04)
The invention provides a preparation method of an aryl propionic acid compound, wherein the preparation method comprises the following steps: carrying out acetylation reaction on substituted aryl benzene to obtain aryl acetophenone; carrying out hydrogenation reduction reaction on alpha-substituted aryl ethyl ketone to obtain alpha-substituted aryl ethanol; and in an acidic solution, introducing carbon monoxide gas into the alpha-substituted aryl ethanol, and carrying out a carbonylation reaction under the co-catalytic action of a main catalyst and a cocatalyst to obtain the aryl propionic acid compound, wherein the cocatalyst has the following structural formula described in the specification, R1 is one of hydrogen and a substituted carboxylic acid group, and R2 is one of hydrogen, halogen, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C12 naphthenic base, substituted carbonyl containing C6-C24 aryl or substitutedaryl, substituted carbonyl containing C3-C12 heterocyclic radical or substituted heterocyclic radical, phenyl, substituted phenyl, naphthyl and substituted naphthyl.
Ketoprofen intermediate as well as preparation method and application thereof
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, (2019/05/02)
The invention relates to the field of medicine synthesis, in particular to a Ketoprofen intermediate as well as a preparation method and application thereof. Ketoprofen is prepared from p--nitrohalobenzene and o-nitrohalobenzene or a mixture of the p-nitrohalobenzene and the o-nitrohalobenzene as raw materials by first performing Diels-Alder reaction on the raw materials and phenylacetonitrile toobtain an isoxazole compound, and then sequentially carrying out oxidation reaction, substitution reaction, reduction reaction, deamination, ester removal and acid hydrolysis reaction to prepare the ketoprofen. The reaction formula is as shown in the specification, wherein X2 and a group as shown in the specification are located in ortho-position or para-position of a nitro group or an amino group, R1 is-CONR4R5,-COX1,-COOR2 or-CN, R2, R3, R4 and R5 are same or differently H or a C1-C6 alkyl group, and X1 and X2 are the same or different, and are F, Cl, Br Or I.
Palladium-Catalyzed α-Arylation of Carboxylic Acids and Secondary Amides via a Traceless Protecting Strategy
He, Zhi-Tao,Hartwig, John F.
supporting information, p. 11749 - 11753 (2019/08/26)
A novel traceless protecting strategy is presented for the long-standing challenge of conducting the palladium-catalyzed α-arylation of carboxylic aids and secondary amides with aryl halides. Both of the presented coupling processes occur with a variety of carboxylic acids and amides and with a variety of aryl bromides containing a broad range of functional groups, including base-sensitive functionality like acyl, alkoxycarbonyl, nitro, cyano, and even hydroxyl groups. Five commercial drugs were prepared through this method in one step in 81-96% yield. Gram-scale synthesis of medication Naproxen and Flurbiprofen with low palladium loading further highlights the practical value of this method.
Method for synthesizing dexketoprofen intermediate
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Paragraph 0036-0039, (2019/01/16)
The invention belongs to the technical field of medicines, and particularly relates to a method for synthesizing a dexketoprofen intermediate. The dexketoprofen intermediate is prepared by asymmetricsynthesis of Darzens reaction. The method can improve the selectivity of the reaction, reduce the loss of raw materials, improve the yield and simplify the operation process, and is conducive to industrial production.
