- Evolution of Glucose Dehydrogenase for Cofactor Regeneration in Bioredox Processes with Denaturing Agents
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Glucose dehydrogenase (GDH) is a general tool for driving nicotinamide (NAD(P)H) regeneration in synthetic biochemistry. An increasing number of synthetic bioreactions are carried out in media containing high amounts of organic cosolvents or hydrophobic substrates/products, which often denature native enzymes, including those for cofactor regeneration. In this work, we attempted to improve the chemical stability of Bacillus megaterium GDH (BmGDHM0) in the presence of large amounts of 1-phenylethanol by directed evolution. Among the resulting mutants, BmGDHM6 (Q252L/E170K/S100P/K166R/V72I/K137R) exhibited a 9.2-fold increase in tolerance against 10 % (v/v) 1-phenylethanol. Moreover, BmGDHM6 was also more stable than BmGDHM0 when exposed to hydrophobic and enzyme-inactivating compounds such as acetophenone, ethyl 2-oxo-4-phenylbutyrate, and ethyl (R)-2-hydroxy-4-phenylbutyrate. Coupled with a Candida glabrata carbonyl reductase, BmGDHM6 was successfully used for the asymmetric reduction of deactivating ethyl 2-oxo-4-phenylbutyrate with total turnover number of 1800 for the nicotinamide cofactor, thus making it attractive for commercial application. Overall, the evolution of chemically robust GDH facilitates its wider use as a general tool for NAD(P)H regeneration in biocatalysis.
- Qian, Wen-Zhuo,Ou, Ling,Li, Chun-Xiu,Pan, Jiang,Xu, Jian-He,Chen, Qi,Zheng, Gao-Wei
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- Asymmetric reduction of 2-oxo-4-phenylbutanoic acid ethyl ester by Daucus carota cell cultures
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A novel method to produce (R)-(-)-2-hydroxy-4-phenylbutanoic acid ethyl ester 1b has been developed 2-Oxo-4-phenylbutanoic acid ethyl ester 1a reduced to 1b by the cell cultures of Daucus carets in high enantiomeric excess and yield.
- Chadha,Manohar,Soundararajan,Lokeswari
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Read Online
- Purification and characterization of carbonyl reductase from Candida krusei SW 2026 involved in enantioselective reduction of ethyl 2-oxo-4-phenylbutyrate
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Optically active ethyl (R)-2-hydroxy-4-phenylbutyrate [(R)-HPBE] is widely used as a key chiral building block in the synthesis of a class of angiotensin-converting enzyme (ACE) inhibitors. A highly enantioselective carbonyl reductase responsible for the reduction of ethyl 2-oxo-4-phenylbutyrate (OPBE) was identified and characterized from Candida krusei SW 2026. The enzyme was purified to homogeneity through three chromatography columns. The relative molecular mass of the enzyme was estimated to be around 45,500 by gel filtration and 46,000 by SDS-polyacrylamide gel electrophoresis. The enzyme yielded (R)-enantiomer product and utilized NADPH as the cofactor. The purified enzyme exhibited maximum activity at pH 6.0 and 30 °C, and retained over 80% of its activity over an acidic pH range of 4.5-7.0. The maximum reaction rate (V max) and apparent Michaelis-Menten constant (Km) for OPBE and NADPH were 18.7 μmol/(min mg) protein and 0.319 mmol, 14.9 μmol/(min mg) protein and 0.306 mmol, respectively.
- Li, Ning,Ni, Ye,Sun, Zhihao
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- Biocatalysed reductions of α-ketoesters employing CyreneTM as cosolvent
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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.
- de Gonzalo, Gonzalo
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- Structure-guided evolution of carbonyl reductase for efficient biosynthesis of ethyl (: R)-2-hydroxy-4-phenylbutyrate
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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.
- Chen, Chao,Chen, Lulu,Deng, Jian,Kuang, Yuyao,Lin, Jinping,Tang, Wen,Wang, Hualei,Wei, Dongzhi,Yin, Bo
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p. 7512 - 7522
(2020/11/27)
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- Methodology Development in Directed Evolution: Exploring Options when Applying Triple-Code Saturation Mutagenesis
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Directed evolution of stereo- or regioselective enzymes as catalysts in asymmetric transformations is of particular interest in organic synthesis. Upon evolving these biocatalysts, screening is the bottleneck. To beat the numbers problem most effectively, methods and strategies for building “small but smart” mutant libraries have been developed. Herein, we compared two different strategies regarding the application of triple-code saturation mutagenesis (TCSM) at multiresidue sites of the Thermoanaerobacter brockii alcohol dehydrogenase by using distinct reduced amino-acid alphabets. By using the synthetically difficult-to-reduce prochiral ketone tetrahydrofuran-3-one as a substrate, highly R- and S-selective variants were obtained (92–99 % ee) with minimal screening. The origin of stereoselectivity was provided by molecular dynamics analyses, which is discussed in terms of the Bürgi–Dunitz trajectory.
- Qu, Ge,Lonsdale, Richard,Yao, Peiyuan,Li, Guangyue,Liu, Beibei,Reetz, Manfred T.,Sun, Zhoutong
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p. 239 - 246
(2018/02/09)
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- Fine tuning the enantioselectivity and substrate specificity of alcohol dehydrogenase from Kluyveromyces polysporus by single residue at 237
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Here, S237 was identified to be important in fine tuning the substrate specificity and enantioselectivity of alcohol dehydrogenase from Kluyveromyces polysporus (KpADH). In the reduction of a diaryl ketone, (4-chlorophenyl)-(pyridin-2-yl)-methanone (1a), the highest and lowest enantioselectivity of 96.1% and 27.0% e.e. (R) were obtained with S237A and S237C. Kinetic parameters analysis revealed that S237G, S237A, S237H and S237D displayed improved kcat/Km toward 1a. Various prochiral ketones, including acetophenone, 4-chloroacetophenone and ethyl 2-oxo-4-phenylbutyrate could be asymmetrically reduced by S237C, S237G and S237E with > 99% e.e. This study provides guidance for the application of KpADH in the preparation of chiral secondary alcohols.
- Wang, Yue,Dai, Wei,Liu, Yongmei,Zhang, Zhongwei,Zhou, Jieyu,Xu, Guochao,Ni, Ye
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- Structural Insight into Enantioselective Inversion of an Alcohol Dehydrogenase Reveals a "polar Gate" in Stereorecognition of Diaryl Ketones
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Diaryl ketones are important building blocks for synthesizing pharmaceuticals and are generally regarded as "difficult-to-reduce" ketones due to the large steric hindrance of their two bulky aromatic side chains. Alcohol dehydrogenase from Kluyveromyces polyspora (KpADH) has been identified as a robust biocatalyst due to its high conversion of diaryl ketone substrate (4-chlorophenyl)(pyridine-2-yl)ketone (CPMK) with a moderate R-selectivity of 82% ee. To modulate the stereoselectivity of KpADH, a "polarity scanning" strategy was proposed, in which six key residues inside and at the entrance of the substrate binding pocket were identified. After iterative combinatorial mutagenesis, variants Mu-R2 and Mu-S5 with enhanced (99.2% ee, R) and inverted (97.8% ee, S) stereoselectivity were obtained. The crystal structures of KpADH and two mutants in complex with NADPH were resolved to elucidate the evolution of enantioselective inversion. Based on MD simulation, Mu-R2-CPMKProR and Mu-S5-CPMKProS were more favorable in the formation of prereaction states. Interestingly, a quadrilateral plane formed by α-carbons of four residues (N136, V161, C237, and G214) was identified at the entrance of the substrate binding pocket of Mu-S5; this plane acts as a "polar gate" for substrates. Due to the discrepancy in charge characteristics between chlorophenyl and pyridine substituents, the pro-S orientation of CPMK is defined when it passes through the "polar gate" in Mu-S5, whereas the similar plane in wild-type is blocked by several aromatic residues. Our result paves the way for engineering stereocomplementary ADH toward bulky diaryl ketones and provides structural insight into the mechanism of stereoselective inversion.
- Zhou, Jieyu,Wang, Yue,Xu, Guochao,Wu, Lian,Han, Ruizhi,Schwaneberg, Ulrich,Rao, Yijian,Zhao, Yi-Lei,Zhou, Jiahai,Ni, Ye
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supporting information
p. 12645 - 12654
(2018/10/05)
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- Asymmetric synthesis of (S)-dihydrokavain from l-malic acid
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A practical and efficient asymmetric synthesis of (S)-dihydrokavain from known ethyl (S)-2-hydroxy-4-phenylbutanoate which is, in turn, readily available from l-malic acid as a cheap chiral pool material is described using regioselective ring-opening of the 1,2-cyclic sulfate with lithium-3,3,3-triethoxypropiolate and subsequent HgO/H2SO4-mediated lactonization as the key steps. Its opposite enantiomer (R)-dihydrokavain was also synthesized from d-malic acid using the same sequences of reactions for the purpose of optical purity determination.
- Eskici, Mustafa,Karanfil, Abdullah,?zer, M. Sabih,Kabak, Yal??n,Durucasu, ?nci
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p. 2382 - 2390
(2018/10/20)
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- A carbonyl reductase from: Candida parapsilosis ATCC 7330: Substrate selectivity and enantiospecificity
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Candida parapsilosis ATCC 7330, a rich source of highly stereospecific oxidoreductases, catalyzes oxidation-reduction of a plethora of compounds yielding industrially important intermediates. An (S)-specific carbonyl reductase (SRED) purified and characterized from this yeast is reported here. (R)-Specific carbonyl reductase (CpCR) was reported by us earlier. SRED asymmetrically reduces ketones with excellent enantiospecificity (ee > 99%) and α-ketoesters with higher catalytic activity but moderate enantiospecificity (ee 70%) in the presence of NADPH. Minimal activity is shown towards the reduction of aldehydes. While the reduction of α-ketoesters with SRED can occur with either NADPH or NADH, for ketone reduction SRED requires NADPH specifically. SRED with a subunit molecular weight of 30 kDa shows optimal activity at pH 5.0 and 25 °C, and its activity is affected by Cu2+. Taken together, SRED and CpCR offer substrates which on asymmetric reduction give products of opposite absolute configurations.
- Sudhakara, Sneha,Chadha, Anju
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supporting information
p. 4165 - 4171
(2017/07/10)
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- Identification of a Robust Carbonyl Reductase for Diastereoselectively Building syn-3,5-Dihydroxy Hexanoate: A Bulky Side Chain of Atorvastatin
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t-Butyl-6-cyano-(3R,5R)-dihydroxyhexanoate is an advanced chiral precursor for the synthesis of the side chain pharmacophore of cholesterol-lowering drug atorvastatin. Herein, a robust carbonyl reductase (LbCR) was newly identified from Lactobacillus brevis, which displays high activity and excellent diastereoselectivity toward bulky t-butyl 6-cyano-(5R)-hydroxy-3-oxo-hexanoate (7). The engineered Escherichia coli cells harboring LbCR and glucose dehydrogenase (for cofactor regeneration) were employed as biocatalysts for the asymmetric reduction of substrate 7. As a result, as much as 300 g L-1 of water-insoluble substrate was completely converted to the corresponding chiral diol with >99.5% de in a space-time yield of 351 g L-1 d-1, indicating a great potential of LbCR for practical synthesis of the very bulky and bi-chiral 3,5-dihydroxy carboxylate side chain of best-selling statin drugs.
- Gong, Xu-Min,Zheng, Gao-Wei,Liu, You-Yan,Xu, Jian-He
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supporting information
p. 1349 - 1354
(2017/09/23)
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- Preparation of structurally diverse chiral alcohols by engineering ketoreductase CgKR1
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Ketoreductases are tools for the synthesis of chiral alcohols in industry. However, the low activity of natural enzymes often restricts their use in industrial applications. On the basis of computational analysis and previous reports, two residues (F92 and F94) probably affecting the activity of ketoreductase CgKR1 were identified. By tuning these two residues, the CgKR1-F92C/F94W variant was obtained that exhibited higher activity toward all 28 structurally diverse substrates examined than the wild-type enzyme. Among them, 13 substrates have a specific activity over 50 U mg-1 (54-775 U mg-1). Using CgKR1-F92C/F94W as a catalyst, five substrates at high loading (>100 g-1 L-1) were reduced completely in gramscale preparative reactions. This approach provides accesses to pharmaceutically relevant chiral alcohols with high enantioselectivity (up to 99.0% ee) and high space-time yield (up to 583 g-1 L-1 day-1). Molecular dynamics simulations highlighted the crucial role of residues 92 and 94 in activity improvement. Our findings provide useful guidance for engineering other ketoreductases, especially those possessing a similar active pocket to that in CgKR1.
- Zheng, Gaowei,Liu, Yuan-Yang,Chen, Qi,Huang, Lei,Yu, Hui-Lei,Lou, Wen-Yong,Li, Chun-Xiu,Bai, Yun-Peng,Li, Ai-Tao,Xu, Jian-He
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p. 7174 - 7181
(2017/11/06)
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- A thermoregulated phase-separable chiral Pt nanocatalyst for recyclable asymmetric hydrogenation of α-ketoesters
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The design and preparation of a chiral Pt nanocatalyst system possessing thermoregulated phase-separation property and its application in recyclable asymmetric hydrogenation of α-ketoesters are presented.
- Xue, Xiuru,Wang, Yanhua,Han, Fu-She
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supporting information
p. 3346 - 3349
(2017/03/22)
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- Chloramphenicol base chemistry. Part 10: Asymmetric synthesis of α-hydroxy chiral alcohols via intramolecular Michael additions of γ-hydroxy-α, β-unsaturated enones with chloramphenicol base derived bifunctional urea organocatalysts
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We have developed the chloramphenicol base urea-catalyzed intramolecular Michael addition of γ-hydroxy-α, β-unsaturated enones. The oxidation of the resulting products provided facile access to the corresponding α-hydroxy chiral alcohols with good efficiency and enantioselectivity, with the reaction displaying broad substrate scope. The utility of this methodology was further demonstrated by the synthesis of (R)-2-hydroxy-4-phenylbutanoate, which is a key building block for the construction of the ACE inhibitor benazepril hydrochloride.
- Wang, Haifeng,Yan, Linjie,Wu, Yan,Chen, Fener
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p. 2793 - 2800
(2017/04/14)
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- Exploring the substrate scope of mutants derived from the robust alcohol dehydrogenase TbSADH
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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.
- Sun, Zhoutong,Li, Guangyue,Ilie, Adriana,Reetz, Manfred T.
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supporting information
p. 3648 - 3651
(2016/07/21)
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- Copper encapsulated alkaloids composite: An effective heterogeneous catalyst for electrocatalytic asymmetric hydrogenation
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A novel heterogeneous catalyst, alkaloid@Cu was prepared by the entrapment of commercially purchased alkaloids within non-noble metallic copper nanoparticles. This composite was compacted into a coin and directly used as cathode for electrocatalytic asymmetric hydrogenation of aromatic ketones. Using water as hydrogen source, optically active alcohols with 71% ee value and 93% yield were obtained under very mild conditions.
- Yang, Heng-Pan,Fen, Qiu,Wang, Huan,Lu, Jia-Xing
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- A process for preparing (R) - 2-hydroxy-4-phenyl-butyric acid ethyl ester method (by machine translation)
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The invention provides a process for preparing (R)? 2? Hydroxy? 4? Phenyl ethyl butyrate method of, in a cheap and easily obtained benzald and pyruvic acid as a raw material, by condensation, esterification, biological enzyme-catalyzed asymmetric reduction and double bond hydrogenated four-step efficient reaction, in order to eventually 82% overall yield of optically pure target product obtained (R)? HPBE. (by machine translation)
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- Method for preparing lisinopril intermediate
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The invention provides a method for preparing a lisinopril intermediate. The lisinopril intermediate is (R)-2-hydroxyl-4-phenylbutyrate. The method has the advantages that the lisinopril intermediate is made of inexpensive and easily available raw materials which are benzaldehyde and pyruvic acid, four-step efficient reaction including condensation, biological enzyme catalytic asymmetric reduction, double-bond hydrogenation and esterification is carried out on the benzaldehyde and the pyruvic acid, and accordingly an optically pure target product (R)-HPBE [(R)-2-hydroxyl-4-phenylbutyrate] can be ultimately obtained at the overall yield of 83%.
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- Improving enantioselectivity of lipase from Candida rugosa by carrier-bound and carrier-free immobilization
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The enantioselectivity of carrier-bound and carrier-free immobilized lipase from Candida rugosa (CRL) was studied. CRL was immobilized in six agarose-based carriers functionalized with different reactive groups and in two different CRL cross-linked aggregates. Both, activity and enantioselectivity of all the immobilized lipase preparations were evaluated with different racemic esters under different reaction conditions (temperature, pH and solvent polarity). A strong effect of reaction media and immobilization protocol on enzyme activity and selectivity was found. Enzyme immobilization and reaction engineering allowed us obtaining the best immobilization protocol and reaction conditions to achieve high activity and enantioselectivty of CRL as heterogeneous catalyst. CRL immobilized on an agarose-based carrier activated with primary amino groups preferentially hydrolyzed (S)-phenylethyl acetate with E > 200 under pH 7, 4 °C and 30% of acetonitrile. On the other hand, CRL aggregated and cross-linked through their carboxylic groups preferentially hydrolyzed the (S)-isomer of ethyl 2-hydroxy-4-phenylbutyrate with an E = 39 under pH 5, 4 °C and 30% of acetonitrile. This work demonstrates the success of the combinatorial enzyme engineering for the production of highly enantioselective heterogeneous biocatalysts by screening different immobilization protocols and reaction media conditions.
- Velasco-Lozano, Susana,López-Gallego, Fernando,Rocha-Martin, Javier,Guisán, José Manuel,Favela-Torres, Ernesto
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- Alkaloid-induced asymmetric hydrogenation on a Cu nanoparticle cathode by electrochemical conditions
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Copper nanoparticles were prepared in an aqueous solution, compacted into a coin, and used as a cathode for asymmetric hydrogenation by the electrochemical method for the first time. A good ee value and excellent yield were obtained under mild conditions. Electrochemical conditions were crucial for alkaloid adsorption on metallic Cu, which is a key process of asymmetric induction. Furthermore, the ee value was linear with an adsorption amount.
- Yang, Heng-Pan,Wang, Huan,Lu, Jia-Xing
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- Chiral Surfactant-Type Catalyst: Enantioselective Reduction of Long-Chain Aliphatic Ketoesters in Water
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A series of amphiphilic ligands were designed and synthesized. The rhodium complexes with the ligands were applied to the asymmetric transfer hydrogenation of broad range of long-chained aliphatic ketoesters in neat water. Quantitative conversion and excellent enantioselectivity (up to 99% ee) was observed for α-, β-, γ-, δ- and ε-ketoesters as well as for α- and β-acyloxyketone using chiral surfactant-type catalyst 2. The CH/π interaction and the strong hydrophobic interaction of long aliphatic chains between the catalyst and the substrate in the metallomicelle core played a key role in the catalytic transition state. Synergistic effects between the metal-catalyzed site and the hydrophobic microenvironment of the core in the micelle contributed to high stereoselectivity. (Chemical Equation Presented).
- Lin, Zechao,Li, Jiahong,Huang, Qingfei,Huang, Qiuya,Wang, Qiwei,Tang, Lei,Gong, Deying,Yang, Jun,Zhu, Jin,Deng, Jingen
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p. 4419 - 4429
(2015/05/13)
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- Effective one-step reduction of Pt/alumina-carbon catalysts for asymmetric hydrogenation of α-ketoesters
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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.
- Zhang, Xueqin,Li, Qiang,Xiao, Meitian,Liu, Yongjun
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- A new class of tunable dendritic diphosphine ligands: Synthesis and applications in the Ru-catalyzed asymmetric hydrogenation of functionalized ketones
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A series of tunable G0-G3 dendritic 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) ligands was prepared by attaching polyaryl ether dendrons onto the four phenyl rings on the P atoms. Their ruthenium complexes were employed in the asymmetric hydrogenation of β-ketoesters, α-ketoesters, and α-ketoamides to reveal the effects of dendron size on the catalytic properties. The second- and third-generation catalysts exhibited excellent enantioselectivities, which are remarkably higher than those obtained from the small molecular catalysts and the first-generation catalyst. Molecular modeling indicates that the incorporation of bulky dendritic wedges can influence the steric environments around the metal center. In addition, the ruthenium catalyst bearing a second-generation dendritic ligand could be recycled and reused seven times without any obvious decrease in enantioselectivity.
- Ma, Baode,Miao, Tingting,Sun, Yihua,He, Yanmei,Liu, Ji,Feng, Yu,Chen, Hui,Fan, Qing-Hua
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supporting information
p. 9969 - 9978
(2014/08/18)
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- A genomic search approach to identify carbonyl reductases in Gluconobacter oxydans for enantioselective reduction of ketones
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The versatile carbonyl reductases from Gluconobacter oxydans in the enantioselective reduction of ketones to the corresponding alcohols were exploited by genome search approach. All purified enzymes showed activities toward the tested ketoesters with different activities. In the reduction of 4-phenyl-2-butanone with in situ NAD(P)H regeneration system, (S)-alcohol was obtained with an e.e. of up to 100% catalyzed by Gox0644. Under the same experimental condition, all enzymes catalyzed ethyl 4-chloroacetoacetate to give chiral products with an excellent e.e. of up to 99%, except Gox0644. Gox2036 had a strict requirement for NADH as the cofactor and showed excellent enantiospecificity in the synthesis of ethyl (R)-4-chloro-3-hydroxybutanoate. For the reduction of ethyl 2-oxo-4-phenylbutyrate, excellent e.e. (>99%) and high conversion (93.1%) were obtained by Gox0525, whereas the other enzymes showed relatively lower e.e. and conversions. Among them, Gox2036 and Gox0525 showed potentials in the synthesis of chiral alcohols as useful biocatalysts.
- Chen, Rong,Liu, Xu,Lin, Jinping,Wei, Dongzhi
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p. 1350 - 1356
(2015/07/27)
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- Pt nanoparticles entrapped in Al2O3?SBA-15 composites: Effective and recyclable catalysts for enantioselective hydrogenation of ethyl 2-oxo-4-phenylbutyrate
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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.
- Li, Xiaohong,Pan, Huiyan,Wang, Haihong,Wang, Yi Meng,Wu, Peng
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- Altering the substrate specificity of reductase CgKR1 from Candida glabrata by protein engineering for bioreduction of aromatic α-keto esters
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A versatile keto ester reductase CgKR1, exhibiting a broad substrate spectrum, was obtained from Candida glabrata by genome data mining. It showed the highest activity toward an aliphatic β-keto ester, ethyl 4-chloro-3-oxobutanoate (COBE), but much lower activity toward bulkier α-keto esters with an aromatic group, such as methyl ortho- chlorobenzoylformate (CBFM) and ethyl 2-oxo-4-phenylbutyrate (OPBE). By rational design of the active pocket, the substrate specificity of the reductase was significantly altered and this tailor-made reductase showed a much higher activity toward aromatic α-keto esters (~7-fold increase in k cat/Km toward CBFM) and lower activity toward aliphatic keto esters (~12-fold decrease in kcat/Km toward COBE). Meanwhile, the thermostability of the reductase was enhanced by a consensus approach. Such improvements may yield practical catalysts for the asymmetric bioreduction of these aromatic α-keto esters
- Huang, Lei,Ma, Hong-Min,Yu, Hui-Lei,Xu, Jian-He
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p. 1943 - 1948
(2014/07/07)
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- Alumina incorporated with mesoporous carbon as a novel support of Pt catalyst for asymmetric hydrogenation
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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.
- Li, Qiang,Zhang, Xueqin,Xiao, Meitian,Liu, Yongjun
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- Ordered mesoporous carbons with Ia3d symmetry supported Pt catalyst for efficient asymmetric hydrogenation
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Pt nanoparticles supported on CMK-8 ordered mesoporous carbons (OMCs) with Ia3d symmetry after chirally modified with cinchonidine (CD) proved to be highly efficient for asymmetric hydrogenation of α-ketoesters. Up to 34,819 h-1 TOF with 75 % ee was furnished for the enantioselective hydrogenation of ethyl 2-oxo-4-phenylbutyrate with CD-modified Pt/CMK-8 catalyst. To the best of our knowledge, these results obtained with chirally modified Pt/CMK-8 catalyst are the best ones among those with Pt catalysts supported on carbon materials. It is suggested that both the physical structure features ofCMK-8 OMCs and the chemical nature of Pt catalyst are beneficial for the asymmetric hydrogenation.
- Li, Bo,Li, Xiaohong,Ding, Yue,Wu, Peng
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p. 1033 - 1039
(2012/10/29)
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- Efficient synthesis of a chiral precursor for angiotensin-converting enzyme (ace) inhibitors in high space-time yield by a new reductase without external cofactors
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A new reductase, CgKR2, with the ability to reduce ethyl 2-oxo-4-phenylbutyrate (OPBE) to ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-HPBE), an important chiral precursor for angiotensin-converting enzyme (ACE) inhibitors, was discovered. For the first time, (R)-HPBE with >99% ee was produced via bioreduction of OPBE at 1 M without external addition of cofactors. The space-time yield (700 g·L-1·d -1) was 27 times higher than the highest record.
- Shen, Nai-Dong,Ni, Yan,Ma, Hong-Min,Wang, Li-Juan,Li, Chun-Xiu,Zheng, Gao-Wei,Zhang, Jie,Xu, Jian-He
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supporting information; experimental part
p. 1982 - 1985
(2012/06/01)
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- Stereospecific reduction of methyl o-chlorobenzoylformate at 300 g·L-1 without additional cofactor using a carbonyl reductase mined from Candida glabrata
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In order to search for oxidoreductases suitable for the preparation of methyl (R)-o-chloromandelate [(R)-CMM], the key intermediate for clopidogrel, the homologous proteins of Gre2p were expressed in Escherichia coli, among which CgKR1 showed the most satisfactory activity and stereoselectivity towards methyl o-chlorobenzoylformate (CBFM). Using the crude enzyme of CgKR1 and glucose dehydrogenase (GDH), as much as 300 g·L-1 of CBFM was almost stoichiometrically converted to (R)-CMM with excellent enantiomeric excess (98.7% ee). More importantly, the reaction could be performed without external addition of an expensive cofactor. The substrate profile indicates that keto esters serve as the most suitable substrate, which was confirmed by gram-scale preparations. Homology modeling and docking analysis revealed the molecular basis for the high stereoselectivity of CgKR1. These demonstrate not only the feasibility of in silico mining of novel enzymes based on sequence homology but also the applicability of this new reductase for the practical production of optically active (R)-CMM. Copyright
- Ma, Hongmin,Yang, Linlin,Ni, Yan,Zhang, Jie,Li, Chun-Xiu,Zheng, Gao-Wei,Yang, Huaiyu,Xu, Jian-He
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experimental part
p. 1765 - 1772
(2012/08/08)
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- Enhancement of the performance of a platinum nanocatalyst confined within carbon nanotubes for asymmetric hydrogenation
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Going through the proper channels: A highly active and enantioselective heterogeneous asymmetric catalyst was fabricated by confining Pt nanoparticles that are modified with cinchonidine within the channels of carbon nanotubes. A high turnover frequency (TOF) and enantioselectivity are achieved when using this catalyst for the asymmetric hydrogenation of α-ketoesters. Copyright
- Chen, Zhijian,Guan, Zaihong,Li, Mingrun,Yang, Qihua,Li, Can
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supporting information; experimental part
p. 4913 - 4917
(2011/06/23)
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- Highly stereoselective reduction of prochiral ketones by a bacterial reductase coupled with cofactor regeneration
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A carbonyl reductase gene (yueD) from Bacillus sp. ECU0013 was heterologously overexpressed in Escherichia coli, and the encoded protein (BYueD) was purified to homogeneity and characterized. The NADPH-dependent reductase showed a broad substrate spectrum towards different aromatic ketones, and α- and β-ketoesters. Although the enantioselectivity was high to moderate for the reduction of α-ketoesters, all the tested β-ketoesters and aromatic ketones were reduced to the corresponding chiral alcohols in enantiomerically pure forms. Furthermore, the practical applicability of this enzyme was evaluated for the reduction of ethyl 4-chloro-3-oxobutanoate (1a). Using Escherichia coli cells coexpressing BYueD and glucose dehydrogenase, 215 g L-1 (1.3 M) of 1a was stoichiometrically converted to ethyl (R)-4-chloro-3-hydroxybutanoate ((R)-1b) in an aqueous-toluene biphasic system by using a substrate fed-batch strategy, resulting in an overall hydroxyl product yield of 91.7% with enantiomeric purity of 99.6% ee.
- Ni, Yan,Li, Chun-Xiu,Wang, Li-Juan,Zhang, Jie,Xu, Jian-He
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experimental part
p. 5463 - 5468
(2011/09/12)
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- Pt nanoparticles entrapped in ordered mesoporous carbon for enantioselective hydrogenation
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Pt nanoparticles entrapped in CMK-3 ordered mesoporous carbon materials, prepared by a facile impregnation method, were found to be efficient for the enantioselective hydrogenation of α-ketoesters by modification with cinchona alkaloids. The initial activity of higher than 23,000 h-1 TOF and 82% ee were obtained for the chiral hydrogenation of ethyl pyruvate with cinchonidine (CD)-modified Pt/CMK-3 catalyst. With regard to the chiral hydrogenation of ethyl 2-oxo-4-phenylbutyrate, the CD-modified Pt/CMK-3 catalyst afforded the highest TOF of 5615 h-1 and 64% ee. For comparison, commercially available Pt/C and Pt/Al2O3 catalysts were investigated as well. The Pt/CMK-3 catalysts were more efficient than the commercial Pt/C catalyst. Of particular note is that the Pt/CMK-3 catalyst exhibited good stability; only below 0.005% Pt atoms were leached into solution after the chiral hydrogenation of ethyl pyruvate in acetic acid, while the Pt leaching amount for the commercial Pt/Al2O3 and Pt/C catalysts was 0.15% and 0.25%, respectively. In addition, the Pt/CMK-3 catalyst could also be reused for more than 5 times without distinct loss of activity and enantioselectivity, while the reusability for the commercial Pt/C and Pt/Al2O3 catalysts was poor. Based on IR and Raman spectroscopic characterization, it is suggested that both the physical structure features, including high specific surface area, adequate pore volume, ordered mesopores and small Pt particle size with high dispersion, and the chemical nature of catalyst surface with high electron density would improve the performance of Pt/CMK-3 catalysts.
- Li, Bo,Li, Xiaohong,Wang, Hongna,Wu, Peng
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experimental part
p. 81 - 89
(2011/10/05)
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- Highly enantioselective hydrogenation of 2-oxo-4-arybutanoic acids to 2-hydroxy-4-arylbutanoic acids
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The Ru-catalyzed asymmetric hydrogenation of 2-oxo-4-arybutanoic acids to afford 2-hydroxy-4-arybutanoic acids was accomplished by employing SunPhos as chiral ligand and 1 M aq HBr as additive. The high enantioselectivities (88.4%-92.6% ee) and efficiency (TON=10,000, TOF=300 h-1) make this method efficient for the synthesis of an important intermediate, (R)-2-hydroxy-4-phenylbutanoic acid, for ACE inhibitors.
- Zhu, Lufeng,Chen, Houhe,Meng, Qinghua,Fan, Weizheng,Xie, Xiaomin,Zhang, Zhaoguo
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supporting information; experimental part
p. 6186 - 6190
(2011/09/19)
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- Chemo-enzymatic synthesis of ethyl (R)-2-hydroxy-4-phenylbutyrate
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A new biocatalytic strategy to obtain the ethyl (R)-2-hydroxy-4-oxo-4- phenylbutyrate precursor of ethyl (R)-2-hydroxy-4-phenylbutyrate, an important intermediate in the synthesis of a variety of ACE inhibitors, has been set up. Starting from ethyl 2,4-dioxo-4-phenylbutyrate, a screen of microorganisms has been performed in order to find the best catalyst able to reduce the keto group in the α-position with high chemo- and enantioselectivity. The biotransformation catalyzed by Pichia pastoris CBS 704 gave the best results in terms of conversion and enantioselectivity. The addition of adsorbing resins in the fermentation medium is effective in controlling substrate and product concentration in the medium, thus improving both conversion and enantioselectivity of the biotransformation. Preliminary experiments in a continuous batch reactor with growing culture of P. pastoris will be also presented.
- D'Arrigo, Paola,Pedrocchi-Fantoni, Giuseppe,Servi, Stefano
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experimental part
p. 914 - 918
(2010/08/19)
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- Direct asymmetric hydrogenation of 2-oxo-4-arylbut-3-enoic acids
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A challenging direct asymmetric hydrogenation of (E)-2-oxo-4-arylbut-3- enoic acids to give 2-hydroxy-4-arylbutanoic acids (85.4-91.8% ee) was achieved with a Ru catalyst based on SunPhos as the chiral ligand. Further investigation of the reaction revealed that partial isomerization of 2-hydroxy-4-arylbutenoic acids was involved in the hydrogenation process. Employing the reaction conditions to the hydrogenation of 2-oxo-4-phenylbutanoic acid resulted in better enantioselectivity (91.8% ee) and efficiency (TON = 2000, TOF = 200 h-1), which offers a useful method for the synthesis of a common intermediate for ACE inhibitors.
- Zhu, Lvfeng,Meng, Qinghua,Fan, Weizheng,Xie, Xiaomin,Zhang, Zhaoguo
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supporting information; experimental part
p. 6027 - 6030
(2010/11/18)
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- Matching and mismatching effects of hybrid chiral biaxial bisphosphine ligands in enantioselective hydrogenation of ketoesters
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A study was conducted to demonstrate matching and mismatching of hybrid chiral biaxial bisphosphine ligands in enantioselective hydrogenation of ketoesters. A novel class of conformationally rigid Cn-TunePhos was developed by introducing a bridge with variable length to link the chiral atropisometic biaryl groups. The conformationally rigid Cn-TunePhos was introduce to investigate the synthesis and use of new chiral biophosphine ligands in asymmetric catalysis. A strategy was introduced for the synthesis of a pair of diastereoisomeric forms of ligands 1, 2, and an analogous ligand 3 to assess the effects of stereochemical matching and mismatching interactions upon the structural and catalytic properties of the corresponding ruthenium complexes. Their applications in highly efficient Ru-catalyzed asymmetric hydrogenation for the enantioselective synthesis of α- and β-hydroxy acid derivatives were also explored.
- Sun, Xianfeng,Li, Wei,Zhou, Le,Zhang, Xumu
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supporting information; scheme or table
p. 7302 - 7305
(2010/03/24)
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- A rapid and green approach to chiral α-hydroxy esters: asymmetric transfer hydrogenation (ATH) of α-keto esters in water by use of surfactants
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A series of α-hydroxy esters were rapidly prepared (1.5 h) from α-keto esters via asymmetric transfer hydrogenation (ATH) in water by the use of surfactants for the first time. This green method, catalyzed by a water-soluble and recyclable Ru(II) complex, gave moderate to high enantioselectivities (up to 99.7% ee) with DTAB as an additive and HCOONa as the hydrogen source.
- Yin, Lu,Jia, Xian,Li, Xingshu,Chan, Albert S.C.
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experimental part
p. 2033 - 2037
(2010/01/16)
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- Stereoselective bioreduction of bulky-bulky ketones by a novel ADH from Ralstonia sp.
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(Figure Presented) Ketones with two bulky substituents, named bulky-bulky ketones, as well as less sterically demanding ketones were successfully reduced to the corresponding optically highly enriched alcohols using a novel identified recombinant short-chain alcohol dehydrogenase RasADH from Ralstonia sp. DSM 6428 overexpressed in E. coli.
- Lavandera, Ivan,Kern, Alexander,Ferreira-Silva, Bianca,Glieder, Anton,De Wildeman, Stefaan,Kroutil, Wolfgang
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p. 6003 - 6005
(2008/12/21)
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- Asymmetric anti-Prelog reduction of ketones catalysed by Paracoccus pantotrophus and Comamonas sp. cells via hydrogen transfer
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A broad range of ketones including methyl-aryl-, methyl-alkyl-, cyclic and sterically hindered ketones were reduced to the corresponding anti-Prelog alcohols with moderate to excellent stereoselectivities by employing lyophilised cells of Paracoccus pantotrophus DSM 11072 and Comamonas sp. DSM 15091 via hydrogen transfer. The reduction equivalents were provided using 2-propanol as a hydride donor. For instance, acetophenone was reduced to the corresponding (R)-enantiomer with >99% ee.
- Lavandera, Ivan,Hoeller, Brigitte,Kern, Alexander,Ellmer, Ursula,Glieder, Anton,de Wildeman, Stefaan,Kroutil, Wolfgang
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p. 1954 - 1958
(2008/12/22)
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- Preparation the key intermediate of angiotensin-converting enzyme (ACE) inhibitors: High enantioselective production of ethyl (R)-2-hydroxy-4- phenylbutyrate with Candida boidinii CIOC21
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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.
- Chen, Yongzheng,Lin, Hui,Xu, Xiaoying,Xia, Shiwen,Wang, Lixin
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scheme or table
p. 426 - 430
(2009/04/08)
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- Asymmetric reduction of substituted α- and β-ketoesters by Bacillus pumilus Phe-C3
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The enantioselective reduction of substituted α- and β-ketoesters using resting cells of Bacillus pumilus Phe-C3 was investigated. Effects of substrate concentration on the catalytic efficiency of the microorganism were studied. Preparative scale productions were carried out under the optimized conditions with 62.4-91.0% yields and 90.2-97.1% ee. The cells retained 80% of initial activity after recycling for six times.
- He, Chunmao,Chang, Dongliang,Zhang, Jie
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p. 1347 - 1351
(2008/12/20)
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- Substituted optically active disphosphine compound
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Provided is a method for producing an optically active compound, in more detail, for producing an optically active compound by asymmetric hydrogenation in a high yield and asymmetric yield. The present invention also provides a catalyst for asymmetric synthesis for the above production method, especially a catalyst for asymmetric hydrogenation, containing a transition metal complex. Further, the present invention provides a new diphosphine compound useful as a ligand of the above transition metal complex and a new transition metal complex containing the above diphosphine compound. The present invention relates to a diphosphine compound represented by the following formula (1): a transition metal complex using the compound, a catalyst for asymmetric synthesis comprising the above transition metal complex and a method for producing an optically active compound using the above catalyst for asymmetric synthesis.
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Page/Page column 100
(2010/11/26)
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- Microbial reduction of ethyl 2-oxo-4-phenylbutyrate. Searching for R-enantioselectivity. New access to the enalapril like ACE inhibitors
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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.
- 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
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p. 1186 - 1188
(2007/10/03)
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- Highly enantioselective hydrogenation of α-keto esters catalyzed by Ru-tunephos complexes
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Various enantiomerically pure α-hydroxy esters were synthesized by asymmetric hydrogenation of α-keto esters catalyzed by Ru-C n-Tunephos complex. Up to 97.1% ee has been achieved for both α-aryl and α-alkyl substituted α-keto esters. Georg Thieme Verlag Stuttgart.
- Wang, Chun-Jiang,Sun, Xianfeng,Zhang, Xumu
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p. 1169 - 1172
(2007/10/03)
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- A new class of versatile chiral-bridged atropisomeric diphosphine ligands: Remarkably efficient ligand syntheses and their applications in highly enantioselective hydrogenation reactions
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A series of chiral diphosphine ligands denoted as PQ-Phos was prepared by atropdiastereoselective Ullmann coupling and ring-closure reactions. The Ullmann coupling reaction of the biaryl diphosphine dioxides is featured by highly efficient central-to-axial chirality transfer with diastereomeric excess >99%. This substrate-directed diastereomeric biaryl coupling reaction is unprecedented for the preparation of chiral diphosphine dioxides, and our method precludes the tedious resolution procedures usually required for preparing enantiomerically pure diphosphine ligands. The effect of chiral recognition was also revealed in a relevant asymmetric ring-closure reaction. The chiral tether bridging the two aryl units creates a conformationally rigid scaffold essential for enantiofacial differentiation; fine-tuning of the ligand scaffold (e.g., dihedral angles) can be achieved by varying the chain length of the chiral tether. The enantiomerically pure Ru- and Ir-PQ-Phos complexes have been prepared and applied to the catalytic enantioselective hydrogenations of α- and β-ketoesters (C=O bond reduction), 2-(6′-methoxy- 2′-naphthyl)-propenoic acid, alkyl-substituted β-dehydroamino acids (C=C bond reduction), and N-heteroaromatic compounds (C=N bond reduction). An excellent level of enantioselection (up to 99.9% ee) has been attained for the catalytic reactions. In addition, the significant ligand dihedral angle effects on the Ir-catalyzed asymmetric hydrogenation of N-heteroaromatic compounds were also revealed.
- Qiu, Liqin,Kwong, Fuk Yee,Wu, Jing,Lam, Wai Har,Chan, Shusun,Yu, Wing-Yiu,Li, Yue-Ming,Guo, Rongwei,Zhou, Zhongyuan,Chan, Albert S. C.
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p. 5955 - 5965
(2007/10/03)
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- Synthesis and application of phosphinoferrocenylaminophosphine ligands for asymmetric catalysis
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(Chemical Equation Presented) A new class of bidentate ligands utilizing a phosphine-aminophosphine structure has been prepared on a ferrocenylethyl backbone in a straightforward and scalable fashion from acetylferrocene. The unique property of the α-ferrocenyl carbonium ion that allows the replacement of a variety of "leaving groups" with retention of configuration greatly facilitates the synthesis, and a number of ligands have been prepared by varying the nitrogen and phosphorus substituents on the aminophosphine. These readily prepared phosphinoferrocenylaminophosphines, known as BoPhoz ligands, show surprising hydrolytic and air stability, with no degradation after 3 years open to the air. The rhodium complexes of these ligands show exceedingly high enantioselectivities (generally > 95% ee) and activities often in excess of 50 000 catalyst turnovers per hour for the asymmetric hydrogenation of a wide variety of dehydro-α-amino acid and itaconic acid derivatives. They also show high activity and good to excellent enantioselectivity for the hydrogenation of a number of α-ketoesters.
- Boaz, Neil W.,Mackenzie, Elaine B.,Debenham, Sheryl D.,Large, Shannon E.,Ponasik Jr., James A.
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p. 1872 - 1880
(2007/10/03)
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- Production of (R)-chiral alcohols by a hydrogen-transfer bioreduction with NADH-dependent Leifsonia alcohol dehydrogenase (LSADH)
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Alcohol dehydrogenase (LSADH) isolated from Leifsonia sp. S749 was used to produce (R)-chiral alcohols. The enzyme with a broad substrate range reduced various prochiral ketones and keto esters to yield optically active secondary alcohols with a high enantiomeric excess. LSADH transferred the pro-S hydrogen of NADH to the carbonyl moiety of phenyl trifluoromethyl ketone 13 through its re face to give (S)-1-phenyl-2,2,2-trifluoroethanol 40. LSADH was able to efficiently reproduce NADH when 2-propanol was used as a hydrogen donor in the reaction mixture.
- Inoue, Kousuke,Makino, Yoshihide,Itoh, Nobuya
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p. 2539 - 2549
(2007/10/03)
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- Tunable dendritic ligands of chiral 1,2-diamine and their application in asymmetric transfer hydrogenation
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Tunable dendritic N-mono-sulfonyl ligands have been designed and synthesized via direct N-mono-sulfonylization of the chiral dendritic vicinal diamines and their ruthenium complexes demonstrated high catalytic and recyclable activities with comparable enantioselectivities to Noyori-Ikariya's TsDPEN-Ru in the asymmetric transfer hydrogenation of an extended range of substrates, such as ketones, keto esters, and olefins.
- Liu, Weiguo,Cui, Xin,Cun, Linfeng,Zhu, Jin,Deng, Jingen
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p. 2525 - 2530
(2007/10/03)
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- Ruthenium catalyzed asymmetric hydrogenation of α- and β-keto esters in ionic liquids using chiral P-Phos ligand
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Chiral dipyridylphosphine ligand P-Phos was used in the Ru catalyzed asymmetric hydrogenation of α- and β-keto esters in room temperature ionic liquids (RTILs) with high conversions and good to excellent enantioselectivities. The catalyst was recycled by simple extraction and reused five times without loss of activity and enantioselectivity.
- Lam, Kim Hung,Xu, Lijin,Feng, Lichun,Ruan, Jiwu,Fan, Qinghua,Chan, Albert S.C.
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p. 903 - 908
(2007/10/03)
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- A highly enantioselective chemoenzymatic synthesis of syn-3-amino-2-hydroxy esters: Key intermediates for taxol side chain and phenylnorstatine
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Starting from the bromination of α-ketoesters to obtain 3-bromo-2-oxoalkanoates and bioreduction with Saccharomyces cerevisiae entrapped in calcium alginate pellets with double gel layers, syn-(2R,3S)-β-bromo- α-hydroxy esters were obtained regioselectively in high yields and high ee. These chiral bromohydrins were cyclized to epoxides that were transformed into oxazolidines and finally opened by acidic hydrolysis to give syn-(2S,3S)-β-amino-α-hydroxy esters in high overall yields and high ee. The enantiomeric excesses of all the intermediates were maintained during the reaction sequence.
- Rodrigues, J. Augusto R.,Milagre, Humberto M. S.,Milagre, Cintia D. F.,Moran, Paulo J. S.
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p. 3099 - 3106
(2007/10/03)
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