51146-56-6Relevant articles and documents
High pressure CO2-controlled reactors: Enzymatic chiral resolution in emulsions
Shang, Wenting,Zhang, Xiaogang,Yang, Xiaoxi,Zhang, Shujuan
, p. 24083 - 24088 (2014)
In this work we have reported the formulation of a CO2-based micelle stabilized by nontoxic TMN series surfactants. Enantioselection of racemic ibuprofen catalyzed by Candida antarctica lipase B (CALB) was used as a model reaction. The effect of reactive parameters, such as temperature, pH, pressure, and water content on reactive environment and conversion has been discussed. For the resolution of racemic ibuprofen in CO2-based micelles, the enzymatic activity reached a high level at 45 °C, with pressure 250 bar, pH 7.4, and water to surfactant ratio W0 25. In addition, the relatively long-chain length in TMN-10 could help the esterification and trans-esterification processes, which resulted in an efficient reaction rate in a CO2-based micelle system. Enzymatic catalysis has been conducted in a CO2-based system rather than in the conventional media to make the enzyme reaction greener. The better resolution efficiency in high pressure CO2-based micelles could be achieved within a relatively short period of time compared with other traditional reactive systems. The Royal Society of Chemistry 2014.
Enantioselective analysis of ibuprofen enantiomers in mice plasma and tissues by high-performance liquid chromatography with fluorescence detection: Application to a pharmacokinetic study
Przejczowska-Pomierny, Katarzyna,W?odyka, Monika,Cios, Agnieszka,Wyska, El?bieta
, p. 500 - 511 (2017)
A direct fluorometric high-performance liquid chromatography (HPLC) method was developed and validated for the analysis of ibuprofen enantiomers in mouse plasma (100?μl) and tissues (brain, liver, kidneys) using liquid–liquid extraction and 4-tertbutylphenoxyacetic acid as an internal standard. Separation of enantiomers was accomplished in a Chiracel OJ-H chiral column based on cellulose tris(4-methylbenzoate) coated on 5?μm silica-gel, 250 x 4.6?mm at 22?°C with a mobile phase composed of n-hexane, 2-propanol, and trifluoroacetic acid that were delivered in gradient elution at a flow rate of 1?ml min?1. A fluorometric detector was set at: λexcit. = 220?nm and λemis. = 290?nm. Method validation included the evaluation of the selectivity, linearity, lower limit of quantification (LLOQ), within-run and between-run precision and accuracy. The LLOQ for the two enantiomers was 0.125 μg ml?1 in plasma, 0.09?μg g?1 in brain, and 0.25?μg g?1 in for liver and kidney homogenates. The calibration curves showed good linearity in the ranges of each enantiomers: from 0.125 to 35?μg ml?1 for plasma, 0.09–1.44?μg g?1 for brain, and 0.25–20?μg g?1 for liver and kidney homogenates. The method was successfully applied to a pharmacokinetic study of ibuprofen enantiomers in mice treated i.v. with 10?mg kg?1 of racemate.
Enzymatic hydrolytic resolution of racemic ibuprofen ethyl ester using an ionic liquid as cosolvent
Wei, Tao,Yang, Kunpeng,Bai, Bing,Zang, Jie,Yu, Xuan,Mao, Duobin
, (2016)
The aim of this study was to develop an ionic liquid (IL) system for the enzymatic resolution of racemic ibuprofen ethyl ester to produce (S)-ibuprofen. Nineteen ILs were selected for use in buffer systems to investigate the effects of ILs as cosolvents for the production of (S)-ibuprofen using thermostable esterase (EST10) from Thermotoga maritima. Analysis of the catalytic efficiency and conformation of EST10 showed that [OmPy][BF4] was the best medium for the EST10-catalyzed production of (S)-ibuprofen. The maximum degree of conversion degree (47.4%), enantiomeric excess of (S)-ibuprofen (96.6%) and enantiomeric ratio of EST10 (177.0) were achieved with an EST10 concentration of 15 mg/mL, racemic ibuprofen ethyl ester concentration of 150 mM, at 75°C, with a reaction time of 10 h. The reaction time needed to achieve the highest yield of (S)-ibuprofen was decreased from 24 h to 10 h. These results are relevant to the proposed application of ILs as solvents for the EST10-catalyzed production of (S)-ibuprofen.
Resolution of (R,S)-ibuprofen catalyzed by immobilized Novozym40086 in organic phase
Yuan, Xin,Wang, Lujun,Liu, Guangyong,Dai, Guilin,Tang, Kewen
, p. 445 - 456 (2019)
The enantioselective esterification of ibuprofen catalyzed by Novozym40086 was successfully conducted in organic solvent. Removing-water reagent was added into the reaction mixture to remove water produced in the esterification. The effects of temperature, n-hexanol concentration, ibuprofen concentration, and loading of enzymes were investigated. Under the condition of equilibrium, the thermodynamic equilibrium constant (K) of 7.697 and enantioselectivity (E) of 8.512 were obtained. The esterification reaction achieved its equilibrium in approximately 30?hours with conversion of 56% and eeS of 93.78%. The predicted values of X and eeS were 67.90% and 95.60%, respectively. The experimental value is approximately equal to the theoretical value, which indicates the feasibility of ideal models.
Facile conversion of racemic ibuprofen to (S)-ibuprofen
Chavez-Flores, David,Salvador, James M.
, p. 237 - 239 (2012)
The methyl ester of ibuprofen was quantitatively formed by Fischer esterification and converted into (S)-ibuprofen in 94% yield with an ee of 94% under dynamic kinetic resolution conditions at pH 9.8, using Candida rugosa lipase, and 20% DMSO. The (R)-methyl ibuprofen ester was observed to racemize by chiral HPLC without the Candida rugosa lipase present. The rates of in situ racemization and enzymatic hydrolysis for the dynamic kinetic resolution were determined to be 0.026 ± 0.004 and 0.053 ± 0.004 h-1, respectively. The rate of enzymatic hydrolysis when no DMSO was present was twice as fast but no racemization occurred. A facile purification of enriched (S)-ibuprofen was developed. Overall, 88% of racemic ibuprofen by weight was converted into (S)-ibuprofen with an ee of 99.7%.
A novel system consisting of easily recyclable dendritic Ru-BINAP catalyst for asymmetric hydrogenation
Deng, Guo-Jun,Fan, Qing-Hua,Chen, Xiao-Min,Liua, Dong-Sheng,Chan, Albert S. C.
, p. 1570 - 1571 (2002)
Dendritic Ru-BINAP catalysts functionalized with alkyl chain at the periphery together with organic binary solvent system that exhibited phase separation induced by addition of a little water have been employed for asymmetric hydrogenation, leading to high catalytic activity and en-antioselectivity as well as facile catalyst recycling.
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.
Asymmetric Markovnikov Hydroaminocarbonylation of Alkenes Enabled by Palladium-Monodentate Phosphoramidite Catalysis
Yao, Ya-Hong,Yang, Hui-Yi,Chen, Ming,Wu, Fei,Xu, Xing-Xing,Guan, Zheng-Hui
supporting information, p. 85 - 91 (2021/01/12)
A palladium-catalyzed asymmetric Markovnikov hydroaminocarbonylation of alkenes with anilines has been developed for the atom-economical synthesis of 2-substituted propanamides bearing an α-stereocenter. A novel phosphoramidite ligand L16 was discovered which exhibited very high reactivity and selectivity in the reaction. This asymmetric Markovnikov hydroaminocarbonylation employs readily available starting materials and tolerates a wide range of functional groups, thus providing a facile and straightforward method for the regio- and enantioselective synthesis of 2-substituted propanamides under ambient conditions. Mechanistic studies revealed that the reaction proceeds through a palladium hydride pathway.