125639-64-7Relevant articles and documents
Microbial reduction of ethyl 2-oxo-4-phenylbutyrate. Searching for R-enantioselectivity. New access to the enalapril like ACE inhibitors
de Lacerda, Paulo S. Bergo,Ribeiro, Joyce Benzaquem,Leite, Selma G.F.,Ferrara, Maria Antonieta,Coelho, Ricardo B.,Bon, Elba P.S.,da Silva Lima, Edson Luiz,Antunes
, p. 1186 - 1188 (2006)
Herein, different microorganisms were tested in the enantioselective reduction of ethyl 2-oxo-4-phenylbutyrate in aqueous medium for the preparation of ethyl (R)-2-hydroxy-4-phenylbutyrate, a key intermediate in the production of angiotensin converting enzyme (ACE) inhibitors. The use of Pichia angusta led to the (R)-enantiomer in 81% ee.
Significantly enhancing the biocatalytic synthesis of chiral alcohols by semi-rationally engineering an anti-Prelog carbonyl reductase from Acetobacter sp. CCTCC M209061
Wei, Ping,Guo, Ze-Wang,Wu, Xiao-Ling,Liang, Shan,Ou, Xiao-Yang,Xu, Pei,Zong, Min-Hua,Yang, Ji-Guo,Lou, Wen-Yong
, (2019)
Chiral alcohols and their derivatives are vital building blocks to synthesize pharmaceutical drugs and high-valued chemicals. Wild-type carbonyl reductase AcCR from Acetobacter sp. has ideal enantioselectivity toward 11 prochiral substrates (e.e.>99%) but poor activity. In this work, a semi-rational engineering was performed to enhance the activity of AcCR. Fortunately, three positive double-mutants (mut-E144A/G152 L, mut-G152 L/Y189 N, and mut-I147 V/G152 L) with specific activity 17–61 folds higher than that of enzyme without modified were achieved. Kinetic studies suggested that the catalytic efficiencies (kcat/Km) of these mutants were also well enhanced. Finally, these modified mut-AcCRs were successfully applied in asymmetric reductions of 11 structurally diverse prochiral substrates (200 mM) with excellent product yields (76.8%–99.1%) and enantiomeric excess (e.e.>99%), which provides an alternative strategy for efficient synthesis of chiral alcohols for pharmaceuticals industry with ideal yield and enantioselectivity.
Effective one-step reduction of Pt/alumina-carbon catalysts for asymmetric hydrogenation of α-ketoesters
Zhang, Xueqin,Li, Qiang,Xiao, Meitian,Liu, Yongjun
, p. 50 - 57 (2014)
Platinum (Pt) particles supported on 15% alumina-carbon composites(Pt/15AM) were reduced by liquid phase reduction methods and one-step high temperature methods. The catalyst was reduced by one-step method with hydrogen at 600°C (Pt/15AM-600) showed superior structure and surface properties such as high special surface area, large pore size, high surface Pt/Al atomic ratio and no residual chlorine on the surface. Moreover, CD-modified Pt/15AM-600 catalyst afforded the highest enantioselectivity of 87.5% and 84.8% in the asymmetric hydrogenation of ethyl pyruvate and EOPB, respectively. Of particular note was the reusability of Pt/15AM-600 catalyst, which could be reused for 23 times without distinct loss in catalytic activity in the asymmetric hydrogenation of ethylpyruvate. The excellent reusability of these alumina-carbon composites supported Pt catalysts indicated the possibility of these novel catalysts in industrial application.
Pt nanoparticles entrapped in Al2O3?SBA-15 composites: Effective and recyclable catalysts for enantioselective hydrogenation of ethyl 2-oxo-4-phenylbutyrate
Li, Xiaohong,Pan, Huiyan,Wang, Haihong,Wang, Yi Meng,Wu, Peng
, p. 48 - 57 (2014)
Solid-state grinding, ultrasonic impregnation and conventional impregnation methods were adopted to synthesize mesoporous composites Al2O3?SBA-15 supported Pt catalysts for chiral hydrogenation of ethyl 2-oxo-4-phenylbutyrate after modified with cinchonidine. Compared with Pt/SBA-15 or Pt/alumina catalyst, Pt/Al2O3?SBA-15 catalysts afforded better results when alumina loading in Al2O3?SBA-15 composites reached above 15 wt.%. Nevertheless, the catalytic performance of Pt/Al2O3?SBA-15 catalysts was affected by preparation methods for Al2O3?SBA-15 composites. Ultrasonic impregnation of SBA-15 with an aqueous solution of aluminum nitrate led to uniformly dispersed Al2O3?SBA-15 composites and then enhanced the interaction between SBA-15 silica and alumina. Correspondingly, the Pt/Al2O3?SBA-15 catalyst prepared by this method showed the best results (up to 11,928 h?1 TOF and 87.9% ee) and could be reused for several times. Based on the spectroscopic characterizations, we deduced that the acidity of the composites, the Pt particle size and dispersion, and the electronic properties of Pt particles played vital roles in determining the catalytic performance.
Exploring the substrate scope of mutants derived from the robust alcohol dehydrogenase TbSADH
Sun, Zhoutong,Li, Guangyue,Ilie, Adriana,Reetz, Manfred T.
, p. 3648 - 3651 (2016)
Directed evolution of an enzyme as catalyst for a given stereoselective transformation provides a mutant for that particular reaction, but organic chemists need catalysts that are characterized by broad substrate acceptance. In a previous study we succeeded in evolving a set of variants of the thermally robust alcohol dehydrogenase TbSADH from Thermoanaerobacter brockii as a catalysts in the (R)- and (S)-selective reduction of tetrahydrofuran-3-one, this difficult-to-reduce compound being a sterically small substrate. These mutants were now tested in the asymmetric reduction of seven structurally unrelated and sterically more demanding substrates, including acetophenone, benzyl methyl ketone, 4-phenyl-2-butanone, and 2-oxo-4-phenyl-butanoic acid ethyl ester. The variants clearly out-perform WT TbSADH, but overly bulky substituted benzophenone derivatives are not accepted by WT or mutants.
Alumina incorporated with mesoporous carbon as a novel support of Pt catalyst for asymmetric hydrogenation
Li, Qiang,Zhang, Xueqin,Xiao, Meitian,Liu, Yongjun
, p. 68 - 72 (2013)
Mesoporous carbon incorporated with different alumina contents has been prepared by chelate-assisted co-assembly method. These composites were used as supports for Pt particles, and the as-prepared catalysts were reduced at 873 K in hydrogen atmosphere. Our current study by using N2 sorption, X-ray diffraction and transmission electron microscopy revealed that carbon incorporated with 10-15 wt% alumina was favorable for the high Pt dispersion and retained the mesostructure of carbon. Moreover, 15 wt% alumina-carbon composite supported Pt particles modified by cinchonidine afforded the highest (84.8%) enantiomeric excess and could be reused at least five times for the asymmetric hydrogenation of ethyl 2-oxo-4-phenylbutyrate in acetic acid.
Preparation the key intermediate of angiotensin-converting enzyme (ACE) inhibitors: High enantioselective production of ethyl (R)-2-hydroxy-4- phenylbutyrate with Candida boidinii CIOC21
Chen, Yongzheng,Lin, Hui,Xu, Xiaoying,Xia, Shiwen,Wang, Lixin
, p. 426 - 430 (2008)
Forty microorganisms belonging to different taxonomicalgroups were used to catalyze the enantioselective reduction of ethyl 2-oxophenylbutyrate to afford the corresponding ethyl2-hy droxy-4-phenylbutyrate. Several microorganisms led to over 99% ee of ethyl(S)-2-hydroxy-4-phenylbutyrate. Especially, we firstly found that the Candida boidinii CIOC21 could be effectively used for the enantioselective preparation the ethyl (R)-2-hydroxy-4-phenylbutyrate in pure aqueous medium with 99% ee, a key intermediate in the production of angiotensin-converting enzyme (ACE) inhibitors.
Enantioselective reduction of C=O and C=N bonds by TADDOL-containing aluminum hydride reagents based on NaAlH4 and AlH3
Vinogradov,Gorshkova,Chel'tsova,Pavlov,Razmanov,Ferapontov,Malyshev,Heise
, p. 471 - 479 (2003)
Prochiral substrates (alkyl aryl ketones, cyclopropyl methyl ketone, 1-indanone, 1-tetralone, ethyl 2-oxo-4-phenylbutyrate, and N- (diphenylphosphinyl)acetophenoneimine) were subjected to asymmetric reduction with aluminum hydride reagents, which were prepared by modifications of NaAlH4 or AlH3 with chiral α,α,α′, α′-tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOL). The effects of the nature of the substituents in TADDOL, the structure of the prochiral substrate, and the reaction conditions on the stereochemistry of reduction were investigated. The highest enantioselectivity (70-90% ee) was achieved upon reduction of alkyl aryl ketones and N-(diphenylphosphinyl)acetophenoneimine with NaAl(TADDOLate)H2 in THF or diglyme at a temperature from -70 to -20°C. The mechanism of asymmetric induction in the reduction reactions of ketones with aluminum hydride reagents is discussed. The stereochemical results of reduction were explained by comparing three-dimensional models of the most probable transition states.
Biocatalysed reductions of α-ketoesters employing CyreneTM as cosolvent
de Gonzalo, Gonzalo
, (2021/02/26)
The search for novel reaction media with environmental friendly properties is an area of great interest in enzyme catalysis. Water is the medium of biocatalysed processes, but due to its properties, sometimes the presence of organic (co)solvents is required. CyreneTM represents one of the newest approaches to this medium engineering. This polar solvent has been employed for the first time in biocatalysed reductions employing purified alcohol dehydrogenases. A set of α-ketoesters has been reduced to the corresponding chiral α-hydroxyesters with high conversions and optical purities, being possible to obtain good results at Cyrene contents of 30% v/v and working at substrate concentrations of 1.0 M in presence of 2.5% v/v of this solvent. At this concentration, the presence of Cyrene has a beneficial effect in the bioreduction conversion.
Structure-guided evolution of carbonyl reductase for efficient biosynthesis of ethyl (: R)-2-hydroxy-4-phenylbutyrate
Chen, Chao,Chen, Lulu,Deng, Jian,Kuang, Yuyao,Lin, Jinping,Tang, Wen,Wang, Hualei,Wei, Dongzhi,Yin, Bo
, p. 7512 - 7522 (2020/11/27)
Ethyl (R)-2-hydroxy-4-phenylbutanoate ((R)-HPBE) is an important versatile intermediate for the synthesis of angiotensin-converting enzyme inhibitors. Herein, a structure-guided rational design was adopted to improve the catalytic performance of carbonyl reductase from Gluconobacter oxydans (GoCR) for efficient production of (R)-HPBE at high substrate loading. To enhance the catalytic performance of GoCR, three sites (Cys93, Ile187 and Trp193) were identified based on a computational approach. Through single-site and cooperative mutation at these three sites, four variants with simultaneous increase in stereoselectivity and catalytic efficiency were obtained. Variants mut-W193L, mut-W193L/C93I, mut-W193L/I187L and mut-W193L/C93I/I187L exhibited 9.8-to 37.0-fold increase in catalytic efficiency (kcat/Km) compared to the wild-type enzyme. Meanwhile, the stereoselectivities of these variants were improved from 43.0% ee of wild-type GoCR to >99% ee. In addition, mut-W193L/C93I/I187L displayed improved thermostability simultaneously. Theoretical structural analysis revealed that the changes in the catalytic pocket microenvironment resulted in the concurrent improvement of enzyme activity and thermostability. In the batch production of (R)-HPBE, up to 371 g L-1 substrate loading was completely reduced by utilizing the most efficient variant mut-W193L/C93I/I187L at 40 °C, affording (R)-HPBE with >99% ee and a space-time yield of 540.4 g L-1 per day. This study provides a potential and attractive biocatalyst for the efficient synthesis of (R)-HPBE.
