- Synthesis and evaluation of a chiral heterogeneous transfer hydrogenation catalyst
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A polymer bound transfer hydrogenation catalyst has been developed based on Noyori's (1S,2S)- or (1R,2R)-N-(p-tolylsulfonyl)-1,2- diphenylethylenediamine. The ruthenium catalysed reduction of acetophenone was examined and the activity of the catalyst was found to be dependent on the type of polymer used. The catalyst was found to be reusable and retained high ee's when HCO2H:Et3N was used as the hydrogen donor.
- Bayston, Daniel J.,Travers, Catherine B.,Polywka, Mario E. C.
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- Asymmetric reduction using N-methyl and N-benzyl oxazaborolidines based upon cis-1-amino-2-indanol: A preliminary mechanistic study
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(1R)-Amino-(2S)-indanol and its N-methyl and N-benzyl derived oxazaborolidines were investigated in the asymmetric reduction of acetophenone in order to obtain insight into the reaction mechanism. Optimisation studies carried out with B-methyl (1R)-amino-(2S)-indanol resulted in enantioselectivities of 84% (by GC) and these applied to a series of aromatic ketones with differing degrees of enantioselectivity.
- Jones, Simon,Atherton
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Read Online
- Unmasking the Hidden Carbonyl Group Using Gold(I) Catalysts and Alcohol Dehydrogenases: Design of a Thermodynamically-Driven Cascade toward Optically Active Halohydrins
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A concurrent cascade combining the use of a gold(I) N-heterocyclic carbene (NHC) and an alcohol dehydrogenase (ADH) is disclosed for the synthesis of highly valuable enantiopure halohydrins in an aqueous medium and under mild reaction conditions. The meth
- González-Granda, Sergio,Escot, Lorena,Lavandera, Iván,Gotor-Fernández, Vicente
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p. 2552 - 2560
(2022/02/16)
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- Cinchona-Alkaloid-Derived NNP Ligand for Iridium-Catalyzed Asymmetric Hydrogenation of Ketones
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Most ligands applied for asymmetric hydrogenation are synthesized via multistep reactions with expensive chemical reagents. Herein, a series of novel and easily accessed cinchona-alkaloid-based NNP ligands have been developed in two steps. By combining [Ir(COD)Cl]2, 39 ketones including aromatic, heteroaryl, and alkyl ketones have been hydrogenated, all affording valuable chiral alcohols with 96.0-99.9% ee. A plausible reaction mechanism was discussed by NMR, HRMS, and DFT, and an activating model involving trihydride was verified.
- Zhang, Lin,Zhang, Ling,Chen, Qian,Li, Linlin,Jiang, Jian,Sun, Hao,Zhao, Chong,Yang, Yuanyong,Li, Chun
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supporting information
p. 415 - 419
(2022/01/12)
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- Enantiocomplementary C–H Bond Hydroxylation Combining Photo-Catalysis and Whole-Cell Biocatalysis in a One-Pot Cascade Process
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Enantiocomplementary hydroxylation of alkyl aromatics through a one-pot photo-biocatalytic cascade reaction is described. The photoredox process is implemented in aqueous phase with O2 as oxidant and the subsequent (R)- or (S)-selective bioreduction is performed by whole cell system without the addition of the expensive cofactor (NADPH). This mild, operationally simple protocol transforms a wide variety of readily available aromatic compounds into valuable chiral alcohols with high yield (up to 90 %) and stereoselectivity (up to 99 %), thereby displaying important potentials in organic synthesis.
- Peng, Yongzhen,Li, Danyang,Fan, Jiajie,Xu, Weihua,Xu, Jian,Yu, Huilei,Lin, Xianfu,Wu, Qi
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p. 821 - 825
(2020/02/20)
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- Deep Eutectic Solvents as Media in Alcohol Dehydrogenase-Catalyzed Reductions of Halogenated Ketones
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The application of deep eutectic solvents (DESs) in biotechnological processes has gained an outstanding relevance, as they can be used as greener media to obtain higher productivities and selectivities. In the present contribution, an eutectic mixture composed of choline chloride (ChCl): glycerol (1 : 2 mol/mol) has been used as a reaction medium in combination with Tris?SO4 50 mM buffer pH 7.5, applied to the alcohol dehydrogenase (ADH)-catalyzed reduction of various carbonyl precursors of chiral halohydrins. These alcohols are key intermediates of biologically active compounds, and hence they are of industrial interest. In the presence of up to 50 % v/v of DES, these biotransformations were achieved up to 300–400 mM of the α-halogenated ketone substrate, getting access to the final compounds with excellent conversions (usually >90 %) and enantiomeric excess (ee >99 %). Among the different ADHs tested, two stereocomplementary enzymes (Lactobacillus brevis ADH and Rhodococcus ruber ADH) afforded the best results, so both alcohol enantiomers could be obtained in all the studied examples. Selected bioreductions were scaled up to 250 mg and 1 g, demonstrating the potential that DESs can offer as media in redox processes for substrates with low solubility in water.
- Ibn Majdoub Hassani, Fatima Zohra,Amzazi, Saaid,Kreit, Joseph,Lavandera, Iván
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p. 832 - 836
(2019/12/24)
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- Cascade bio-hydroxylation and dehalogenation for one-pot enantioselective synthesis of optically active β-halohydrins from halohydrocarbons
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A stereoselective hydroxylation and enantioselective dehalogenation cascade reaction was developed for the synthesis of optically active β-haloalcohols from halohydrocarbons. This cascade system employed P450 and halohydrin dehalogenase as two compatible biocatalysts, allowing a straightforward, greener and efficient access to β-halohydrins with excellent enantioselectivities (98-99%).
- Cui, Hai-Bo,Xie, Ling-Zhi,Wan, Nan-Wei,He, Qing,Li, Zhi,Chen, Yong-Zheng
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supporting information
p. 4324 - 4328
(2019/08/21)
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- Enhanced activity and modified substrate-favoritism of Burkholderia cepacia lipase by the treatment with a pyridinium alkyl-PEG sulfate ionic liquid
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Three types of pyridinium salts, i.e., 1-ethylpyridin-1-ium cetyl-PEG10 sulfate (PYET), 1-butylpyridin-1-ium cetyl-PEG10 sulfate (PYBU), and 1-(3-methoxypropyl)pyridin-1-ium cetyl-PEG10 sulfate (PYMP), have been prepared and evaluated for their activation property of Burkholderia cepacia lipase by comparison to the control IL-coated enzymes, 1-butyl-2,3-dimethylimidazolium cetyl-PEG10 sulfate-coated lipase PS (IL1-PS). Among the tested pyridinium salt-coated lipases, the PYET-coated lipase PS (PYET-PS) exhibited the best results; the transesterification of 1-(pyridin-2-yl)ethanol, 1-(pyridin-3-yl)ethanol, 1-(pyridin-4-yl)ethanol, or 4-phenylbut-3-en-2-ol proceeded faster than those of the IL1-PS-catalyzed reaction while maintaining an excellent enantioselectivity (E > 200). This improved efficiency was found to be dependent on the increased Kcat value.
- Kadotani, Shiho,Nokami, Toshiki,Itoh, Toshiyuki
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p. 441 - 447
(2019/01/04)
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- Exploring the Biocatalytic Scope of a Novel Enantioselective Halohydrin Dehalogenase from an Alphaproteobacterium
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A gene encoding halohydrin dehalogenase from an alphaproteobacterium (AbHHDH) was identified, cloned and over-expressed in Escherichia coli. AbHHDH was able to catalyze the stereoselective dehalogenation of prochiral and racemic halohydrins. It showed the highest enantioselectivity in the dehalogenation of 20?mM (R,S)-2-bromo-1-phenylethanol, which yielded (S)-2-bromo-1-phenylethanol with 99% ee and 34.5% yield. Moreover, AbHHDH catalyzed the azidolysis of epoxides with low to moderate (S)-enantioselectivity. The highest enantioselectivity (E = 18.6) was observed when (R,S)-benzyl glycidyl ether was used as the substrate. A sequential kinetic resolution catalyzed by HHDH was employed for the synthesis of chiral 1-chloro-3-phenoxy-2-propanol. We prepared enantiopure (S)-isomer with a high enantiopurity of ee > 99% and a yield of 30.7% (E-value: 21.3) by kinetic resolution of 20?mM substrate. The (S)-isomer with 99% ee readily obtained from 40 to 150?mM (R,S)-1-chloro-3-phenoxy-2-propanol. Taken together, the results of this study demonstrate the applicability of this HHDH for the production of optically active compounds. [Figure not available: see fulltext.].
- Xue, Feng,Ya, Xiangju,Xiu, Yuansong,Tong, Qi,Wang, Yuqi,Zhu, Xinhai,Huang, He
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p. 629 - 637
(2019/01/25)
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- Enantioselective Reduction of α,β-Unsaturated Ketones and Aryl Ketones by Perakine Reductase
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This report describes the enantioselective reduction of structurally diverse α,β-unsaturated ketones and aryl ketones by perakine reductase (PR) from Rauvolfia. This enzymatic reduction produces α-chiral allylic and aryl alcohols with excellent enantioselectivity and most of the products in satisfactory yields. Furthermore, the work demonstrates 1 mmol scale reactions for product delivery without any detrimental effect on yield and enantioselectivity. The catalytic mechanism, determined by 3D-structure-based modeling of PR and ligand complexes, is also described.
- Cai, Sheng,Shao, Nana,Chen, Yuanyuan,Li, Anbang,Pan, Jie,Zhu, Huajian,Zou, Hongbin,Zeng, Su,Sun, Lianli,Zhao, Jinhao
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supporting information
p. 4411 - 4414
(2019/05/22)
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- Two enantiocomplementary ephedrine dehydrogenases from arthrobacter sp. TS-15 with broad substrate specificity
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The recently identified pseudoephedrine and ephedrine dehydrogenases (PseDH and EDH, respectively) from Arthrobacter sp. TS-15 are NADH-dependent members of the oxidoreductase superfamily of short-chain dehydrogenases/reductases (SDRs). They are specific for the enantioselective oxidation of (+)-(S) N-(pseudo)ephedrine and (-)-(R) N-(pseudo)ephedrine, respectively. Anti-Prelog stereospecific PseDH and Prelog-specific EDH catalyze the regio- A nd enantiospecific reduction of 1-phenyl-1,2-propanedione to (S)-phenylacetylcarbinol and (R)-phenylacetylcarbinol with full conversion and enantiomeric excess of >99%. Moreover, they perform the reduction of a wide range of aryl-aliphatic carbonyl compounds, including ketoamines, ketoesters, and haloketones, to the corresponding enantiopure alcohols. The highest stability of PseDH and EDH was determined to be at a pH range of 6.0-8.0 and 7.5-8.5, respectively. PseDH was more stable than EDH at 25 °C with half-lives of 279 and 38 h, respectively. However, EDH is more stable at 40 °C with a 2-fold greater half-life than at 25 °C. The crystal structure of the PseDH-NAD+ complex, refined to a resolution of 1.83 ?, revealed a tetrameric structure, which was confirmed by solution studies. A model of the active site in complex with NAD+ and 1-phenyl-1,2-propanedione suggested key roles for S143 and W152 in recognition of the substrate and positioning for the reduction reaction. The wide substrate spectrum of these dehydrogenases, combined with their regio- A nd enantioselectivity, suggests a high potential for the industrial production of valuable chiral compounds.
- Shanati, Tarek,Lockie, Cameron,Beloti, Lilian,Grogan, Gideon,Ansorge-Schumacher, Marion B.
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p. 6202 - 6211
(2019/08/15)
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- Immobilized and free cells of geotrichum candidum for asymmetric reduction of ketones: Stability and recyclability
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Marine-derived fungus Geotrichum candidum AS 2.361 was previously reported by our group as an active strain for the enantioselective reduction of ketones. Although some other Geotrichum strains were also found from the terrestrial sources, information on their stability and reusability is scarce. Herein, the stabilities—in terms of pH tolerance, thermostability, and storage stability, and reusability—of G. candidum AS 2.361 were described for the asymmetric reduction of a series of aromatic ketones. Two differently immobilized cells (agar immobilization and calcium alginate immobilization) as well as free cells were prepared. For three substrates (1-(3-bromophenyl) ethan-1-one (1b), 1-(2-chlorophenyl) ethan-1-one (1d), and acetophenone (1g)) immobilized cells on agar showed a great improvement in the bioreduction activities compared to the free cells, increasing yields up to 97% with ee values of 99%. Cells immobilized on agar/calcium alginate could maintain more than 90% of the original activities within the assayed pH ranges of 3.5–11, while free cells were highly sensitive to alkaline and acidic conditions. Concerning thermostability, immobilized cells on agar kept 99% of their original activities after incubation at 60?C for 1 h, while almost no activity was detected for the free cells under the same condition. Immobilized cells were stable at 4?C for 80 days without any activity loss, while free cells started to decrease the activity after storage at 4?C for six days. The immobilized cells retained almost 99% activity after four reuse cycles, while free cells lost almost all the activities at on the third cycle.
- Liu, Hui,de Souza, Fayene Zeferino Ribeiro,Liu, Lan,Chen, Bi-Shuang
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- Ultrafast Iron-Catalyzed Reduction of Functionalized Ketones: Highly Enantioselective Synthesis of Halohydrines, Oxaheterocycles, and Aminoalcohols
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A molecularly defined chiral boxmi iron alkyl complex catalyzes the hydroboration of various functionalized ketones and provides the corresponding chiral halohydrines, oxaheterocycles (oxiranes, oxetanes, tetrahydrofurans, and dioxanes) and amino alcohols with excellent enantioselectivities (up to >99 %ee) and conversion efficiencies at low catalyst loadings (as low as 0.5 mol %). Turnover frequencies of greater than 40000 h?1 at ?30 °C highlight the activity of this earth-abundant metal catalyst which tolerates a large number of functional groups.
- Blasius, Clemens K.,Vasilenko, Vladislav,Gade, Lutz H.
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supporting information
p. 10231 - 10235
(2018/07/31)
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- Iridium-Catalyzed Asymmetric Hydrogenation of Halogenated Ketones for the Efficient Construction of Chiral Halohydrins
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Iridium-catalyzed asymmetric hydrogenation of prochiral halogenated ketones was successfully developed to prepare various chiral halohydrins with high reactivities and excellent enantioselectivities under basic reaction condition (up to >99% conversion, 99% yield, >99% ee). Moreover, gram-scale experiment was performed well in the presence of just 0.005 mol% (S/C=20 000) Ir/f-amphox catalyst with 99% yield and >99% ee. (Figure presented.).
- Yin, Congcong,Wu, Weilong,Hu, Yang,Tan, Xuefeng,You, Cai,Liu, Yuanhua,Chen, Ziyi,Dong, Xiu-Qin,Zhang, Xumu
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p. 2119 - 2124
(2018/04/30)
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- Acylative Kinetic Resolution of Alcohols Using a Recyclable Polymer-Supported Isothiourea Catalyst in Batch and Flow
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A polystyrene-supported isothiourea catalyst, based on the homogeneous catalyst HyperBTM, has been prepared and used for the acylative kinetic resolution of secondary alcohols. A wide range of alcohols, including benzylic, allylic, and propargylic alcohols, cycloalkanol derivatives, and a 1,2-diol, has been resolved using either propionic or isobutyric anhydride with good to excellent selectivity factors obtained (28 examples, s values up to 600). The catalyst can be recovered and reused by a simple filtration and washing sequence, with no special precautions needed. The recyclability of the catalyst was demonstrated (15 cycles) with no significant loss in either activity or selectivity. The recyclable catalyst was also used for the sequential resolution of 10 different alcohols using different anhydrides with no cross-contamination between cycles. Finally, successful application in a continuous flow process demonstrated the first example of an immobilized Lewis base catalyst used for the kinetic resolution of alcohols in flow.
- Neyyappadath, Rifahath Mon,Chisholm, Ross,Greenhalgh, Mark D.,Rodríguez-Escrich, Carles,Pericàs, Miquel A.,H?hner, Georg,Smith, Andrew D.
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p. 1067 - 1075
(2018/02/14)
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- Selective Asymmetric Transfer Hydrogenation of α-Substituted Acetophenones with Bifunctional Oxo-Tethered Ruthenium(II) Catalysts
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A practical method for the asymmetric transfer hydrogenation of α-substituted ketones was developed utilizing oxo-tethered N-sulfonyldiamine-ruthenium complexes. Reduction by HCO2H and HCO2K in a mixed solvent of EtOAc/H2O allowed for the selective synthesis of halohydrins from 2-bromoacetophenone (98%) and 2-chloroacetophenone (>99%), leading to suppressed undesired side reactions stemming from formylation under the typical reaction conditions using an azeotropic 5:2 mixture of HCO2H and Et3N. A range of functional groups, such as halogens, methoxy, nitro, dimethylamino, and ester groups, were well tolerated, highlighting the potential of this method. Nearly complete selectivity with a preferable ee was maintained even with a substrate/catalyst (S/C) ratio of 5000. This catalyst system was also effective for the asymmetric reduction of α-sulfonated ketones without eroding the leaving group. (Figure presented.).
- Yuki, Yamato,Touge, Taichiro,Nara, Hideki,Matsumura, Kazuhiko,Fujiwhara, Mitsuhiko,Kayaki, Yoshihito,Ikariya, Takao
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supporting information
p. 568 - 574
(2017/12/13)
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- N,O- vs N,C-Chelation in Half-Sandwich Iridium Complexes: A Dramatic Effect on Enantioselectivity in Asymmetric Transfer Hydrogenation of Ketones
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Cyclometalation of [Cp?IrCl2]2 with methyl (S)-2-phenyl-4,5-dihydrooxazole-4-carboxylate in the presence of NaOAc selectively led to a N,C- or N,O-chelated Cp?Ir(III) complex, depending on whether or not water was present in the reaction. While derived from the same precursor, these two complexes behaved in a dramatically different manner in asymmetric transfer hydrogenation (ATH) of ketones by formic acid, with the N,O-chelated complex being much more selective and active. The sense of asymmetric induction is also different, with the N,O-complex affording S while the N,C-analogue R alcohols. Further study revealed that the nature of the base additive considerably impacts the enantioselectivity and the effective HCOOH/amine ratios. These observations show the importance of ligand coordination mode and using the right base for ATH reactions.
- Zhou, Gang,Aboo, Ahmed H.,Robertson, Craig M.,Liu, Ruixia,Li, Zhenhua,Luzyanin, Konstantin,Berry, Neil G.,Chen, Weiping,Xiao, Jianliang
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p. 8020 - 8026
(2018/09/06)
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- Accessible Bifunctional Oxy-Tethered Ruthenium(II) Catalysts for Asymmetric Transfer Hydrogenation
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A concise synthesis of new oxy-tethered ruthenium complexes effective for the asymmetric transfer hydrogenation of aromatic ketones is described. The oxy-tether was constructed via a defluorinative etherification arising from an intramolecular nucleophilic substitution of a perfluorinated phenylsulfonyl substituent. The obtained tethered complexes exhibited desirable catalytic activity and selectivity, especially in the asymmetric transfer hydrogenation of functionalized aromatic ketones. The robustness and rigidity of the tether contribute to their superior catalytic performance relative to the nontethered prototype complex.
- Matsunami, Asuka,Ikeda, Marika,Nakamura, Hitomi,Yoshida, Minori,Kuwata, Shigeki,Kayaki, Yoshihito
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supporting information
p. 5213 - 5218
(2018/09/13)
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- Immobilization of Amano lipase from Pseudomonas fluorescens on silk fibroin spheres: an alternative protocol for the enantioselective synthesis of halohydrins
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The search for a new, efficient, cheaper and sustainable matrix for lipase immobilization is a growing area in biotechnology. Amano lipase from Pseudomonas fluorescens was immobilized on silk fibroin spheres and used in the enzymatic kinetic resolution of halohydrins, to obtain optically active epoxides (up to 99% ee), important precursors in the synthesis of derivative antifungal azoles. This paper reinforces the versatility of silk fibroin as a support for heterogeneous catalysts.
- Ferreira, Irlon M.,Yoshioka, Sergio A.,Comasseto, Jo?o V.,Porto, André L. M.
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p. 12650 - 12658
(2017/03/11)
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- Synthetically useful variants of industrial lipases from: Burkholderia cepacia and Pseudomonas fluorescens
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Industrial enzymes lipase PS (LPS) and lipase AK (LAK), which originate from Burkholderia cepacia and Pseudomonas fluorescens, respectively, are synthetically useful biocatalysts. To strengthen their catalytic performances, we introduced two mutations into hot spots of the active sites (residues 287 and 290). The LPS-L287F/I290A double mutant showed high catalytic activity and enantioselectivity for poor substrates for which the wild-type enzyme showed very low activity. The LAK-V287F/I290A double mutant was also an excellent biocatalyst with expanded substrate scope, which was comparable to the LPS-L287F/I290A double mutant. Thermodynamic parameters were determined to address the origin of the high enantioselectivity of the double mutant. The ΔΔH? term, but not the ΔΔS? term, was predominant, which suggests that the enantioselectivity is driven by a differential energy associated with intermolecular interactions around Phe287 and Ala290. A remarkable solvent effect was observed, giving a bell-shaped profile between the E values and the log&P or ? values of solvents with the highest E value in i-Pr2O. This suggests that an organic solvent with appropriate hydrophobicity and polarity provides the double mutant with some flexibility that is essential for excellent catalytic performance.
- Yoshida, Kazunori,Ono, Masakazu,Yamamoto, Takahiro,Utsumi, Takashi,Koikeda, Satoshi,Ema, Tadashi
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supporting information
p. 8713 - 8719
(2017/11/03)
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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 enantiomerically enriched aromatic β-hydroxynitriles and halohydrins by ketone reduction with recombinant ketoreductase KRED1-Pglu
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A NADPH-dependent benzil reductase (KRED1-Pglu) was used as recombinant enzyme for catalysing the reduction of different functionalised ketones. The reactions were carried out in the presence of a catalytic amount of NADP+and an enzyme-coupled transformation (oxidation of glucose catalysed by glucose dehydrogenase), for regenerating the cofactor and thus driving the reaction to completion. KRED1-Pglu showed remarkable versatility, being able to reduce different β-ketonitriles and α-haloketones at different pHs; notably, depending on the nature of the substrate, KRED1-Pglu can be used for efficient and clean enzymatic reduction, avoiding side-reactions due to the pH of the medium. The reduction generally occurred with high enantioselectivity, allowing the preparation of enantiomerically enriched β-hydroxynitriles and halohydrins in high yields; the stereochemical outcome of the reduction followed in all the cases the so-called Prelog's rule.
- Contente, Martina L.,Serra, Immacolata,Molinari, Francesco,Gandolfi, Raffaella,Pinto, Andrea,Romano, Diego
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p. 3974 - 3979
(2016/07/06)
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- A convenient enantioselective CBS-reduction of arylketones in flow-microreactor systems
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A convenient, versatile, and green CBS-asymmetric reduction of aryl and heteroaryl ketones has been developed by using the microreactor technology. The study demonstrates that it is possible to handle borane solution safely within microreactors and that the reaction performs well using 2-MeTHF as a greener solvent.
- De Angelis, Sonia,De Renzo, Maddalena,Carlucci, Claudia,Degennaro, Leonardo,Luisi, Renzo
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supporting information
p. 4304 - 4311
(2016/05/24)
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- Synthesis of enantiopure epoxide by 'one pot' chemoenzymatic approach using a highly enantioselective dehydrogenase
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Enantiopure α-phenethyl alcohols, including aromatic halohydrins, are important chiral building blocks. One of the best approaches to synthesise α-phenethyl alcohols is asymmetric reduction of prochiral ketones by alcohol dehydrogenases (ADHs). The obtained enantiopure halohydrin could be directly used to produce enantiopure epoxide through a base-induced ring-closure reaction, which is an attractive 'one pot' chemoenzymatic method for producing high-yield epoxide. In this study, a novel medium-chain dehydrogenase (KcDH) from Kuraishia capsulate CBS1993 was identified and characterised to show its broad substrate scope and excellent enantioselectivity. KcDH showed activities on 25 substrates of the 26 tested aromatic ketones and heteroaryl ketones, with an enantiomeric excess (ee) >99% and the highest relative activity observed with para-nitro acetophenone. Due to its high enantioselectivity for α-haloketones, a chemoenzymatic method for the synthesis of enantiopure styrene oxide (SO) and phenyl glycidyl ether (PGE) was developed through a base-induced ring-closure reaction on enantiopure halohydrin obtained with KcDH. (R)-SO and (S)-PGE were obtained in 86% and 94% analytical yield, respectively, and both epoxides were obtained with ee >99%. Thus, our results suggested that KcDH may be a promising biocatalyst for the production of multiple enantiopure α-phenethyl alcohols and epoxides.
- Wu, Kai,Chen, Lifeng,Fan, Haiyang,Zhao, Zhiqiang,Wang, Hualei,Wei, Dongzhi
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p. 899 - 904
(2016/02/05)
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- One-Pot cascade hydration-asymmetric transfer hydrogenation as a practical strategy to construct chiral β-adrenergic receptor blockers
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The facile construction of biologically active β-adrenergic receptor agonists/blockers and analogues is a great fundamental and practical challenge in medical chemistry. Herein, we report a hydration-asymmetric transfer hydrogenation cascade to realize the one-pot enantioselective transformation of aromatic haloalkynes into chiral aromatic halohydrins, which can be converted readily into chiral β-adrenergicreceptor blockers. Such a one-pot cascade process involves the Au-catalyzed hydration of aryl-substituted haloalkynes to aryl-substituted α-halomethyl ketones and the Ru-catalyzed asymmetric transfer hydrogenation of aryl-substituted α-halomethyl ketones to aryl-substituted 2-haloethanols. The significant benefits of this procedure are that it provides chiral aromatic halohydrins in high yields, with excellent enantioselectivities, and a wide variety of functional groups are tolerated under mild conditions. The study described herein offers a useful approach to construct chiral β-adrenergic blockers, which is an attractive practical organic transformation that is performed in a one-pot manner.
- Ye, Qunqun,Cheng, Tanyu,Zhao, Yuxi,Zhao, Junwei,Jin, Ronghua,Liu, Guohua
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p. 1801 - 1805
(2015/06/23)
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- Chiral terpene auxiliaries III: Spiroborate esters from (1R,2S,3R,5R)-3-amino-apopinan-2-ol as highly effective catalysts for asymmetric reduction of ketones with borane
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New spiroborate esters, derived from terpene amino alcohols, (S)-prolinol, and 2-aminoethanol, were employed as catalysts in the borane reduction of acetophenone and other aryl alkyl and halogenated ketones. The corresponding alcohols were obtained in high yields and with enantioselectivities up to 98% ee. The influence of the amino alcohol and the diol moieties of spiroborate on the reaction selectivity was examined. The catalyst load, the nature of the solvent, the borane source, and the reaction conditions were also investigated.
- ?wiklińska, Marta,Krzemiński, Marek P.,Tafelska-Kaczmarek, Agnieszka
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p. 1453 - 1458
(2015/12/09)
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- Enantioselective bioreductive preparation of chiral halohydrins employing two newly identified stereocomplementary reductases
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Two robust stereocomplementary carbonyl reductases (DhCR and CgCR) were identified through rescreening the carbonyl reductase toolbox. Five reductases were returned through the activity and enantioselectivity assay for α-chloro-1-acetophenone and ethyl 4-chloro-3-oxo-butanate (COBE). Three reductases were stable at elevated substrate loading. Enzymatic characterization revealed that DhCR and CgCR were more thermostable. As much as 330 g COBE in 1 L biphasic reaction mixture was reduced to (S)- and (R)-3-hydroxy-4-chlorobutyrate by DhCR and CgCR (coexpressed with glucose dehydrogenase), with 92.5% and 93.0% yields, >99% ee, and total turnover numbers of 53800 and 108000, respectively. Six other α-halohydrins were asymmetrically reduced to optically pure forms at a substrate loading of 100 g L-1. Our results indicate the potential of these two stereocomplementary reductases in the synthesis of valuable α-halohydrins for pharmaceuticals. This journal is
- Xu, Guo-Chao,Yu, Hui-Lei,Shang, Yue-Peng,Xu, Jian-He
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p. 22703 - 22711
(2015/03/14)
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- Identification of an ε-keto ester reductase for the efficient synthesis of an (R)-α-lipoic acid precursor
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Abstract A novel reductase (CpAR2) with unusually high activity toward an ε-keto ester, ethyl 8-chloro-6-oxooctanoate, was isolated from Candida parapsilosis. The asymmetric reduction of ethyl 8-chloro-6-oxooctanoate using Escherichia coli cells coexpressing CpAR2 and glucose dehydrogenase genes gave ethyl (R)-8-chloro-6-hydroxyoctanoate, a key precursor for the synthesis of (R)-α-lipoic acid, in high space-time yield (530 gL-1d-1) and with excellent enantiomeric excess (>99%). This bioprocess was shown to be viable on a 10-L scale. This method provides a greener and more cost-effective method for the industrial production of (R)-α-lipoic acid.
- Zhang, Yu-Jun,Zhang, Wen-Xia,Zheng, Gao-Wei,Xu, Jian-He
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supporting information
p. 1697 - 1702
(2015/06/02)
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- Easy to Synthesize, Robust Organo-osmium Asymmetric Transfer Hydrogenation Catalysts
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Asymmetric transfer hydrogenation (ATH) is an important process in organic synthesis for which the Noyori-type RuII catalysts [(arene)Ru(Tsdiamine)] are now well established and widely used. We now demonstrate for the first time the catalytic a
- Coverdale, James P. C.,Sanchez-Cano, Carlos,Clarkson, Guy J.,Soni, Rina,Wills, Martin,Sadler, Peter J.
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supporting information
p. 8043 - 8046
(2015/05/27)
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- Unusually Broad Substrate Profile of Self-Sufficient Cytochrome P450 Monooxygenase CYP116B4 from Labrenzia aggregata
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A new member of the CYP116B subfamily - P450LaMO - was discovered in Labrenzia aggregata by genomic data mining. It was successfully overexpressed in Escherichia coli, purified, and subsequently characterized spectroscopically, and its catalytic properties were assessed. Substrate profiling of the P450LaMO revealed that it was a versatile catalyst, exhibiting hydroxylation and epoxidation activities as well as O-dealkylation and asymmetric sulfoxidation activities. Diverse compounds, including alkylbenzenes, aromatic bicyclic molecules, and terpenoids, were shown to be hydroxylated by P450LaMO. Such diverse catalytic activities are uncommon for the bacterial P450s, and the P450LaMO -mediated stereoselective hydroxylation of inactivated C - H bonds - ubiquitous and relatively unreactive in organic molecules - is particularly unusual. The self-sufficient nature of P450LaMO, coupled with its broad substrate range, highlights it as an ideal template for directed evolution towards various applications.
- Yin, Yue-Cai,Yu, Hui-Lei,Luan, Zheng-Jiao,Li, Ren-Jie,Ouyang, Peng-Fei,Liu, Jing,Xu, Jian-He
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p. 2443 - 2449
(2015/03/03)
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- Unusually Broad Substrate Profile of Self-Sufficient Cytochrome P450 Monooxygenase CYP116B4 from Labrenzia aggregata
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A new member of the CYP116B subfamily - P450LaMO - was discovered in Labrenzia aggregata by genomic data mining. It was successfully overexpressed in Escherichia coli, purified, and subsequently characterized spectroscopically, and its catalytic properties were assessed. Substrate profiling of the P450LaMO revealed that it was a versatile catalyst, exhibiting hydroxylation and epoxidation activities as well as O-dealkylation and asymmetric sulfoxidation activities. Diverse compounds, including alkylbenzenes, aromatic bicyclic molecules, and terpenoids, were shown to be hydroxylated by P450LaMO. Such diverse catalytic activities are uncommon for the bacterial P450s, and the P450LaMO -mediated stereoselective hydroxylation of inactivated C-H bonds - ubiquitous and relatively unreactive in organic molecules - is particularly unusual. The self-sufficient nature of P450LaMO, coupled with its broad substrate range, highlights it as an ideal template for directed evolution towards various applications.
- Yin, Yue-Cai,Yu, Hui-Lei,Luan, Zheng-Jiao,Li, Ren-Jie,Ouyang, Peng-Fei,Liu, Jing,Xu, Jian-He
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p. 2443 - 2449
(2015/08/24)
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- Highly enantioselective acylation of chlorohydrins using Amano AK lipase from P. fluorescens immobilized on silk fibroin-alginate spheres
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Aromatic, allylic, and aliphatic compounds containing a chlorohydrin group were selected as substrates for the enzymatic kinetic resolution mediated by Amano AK lipase from Pseudomonas fluorescens immobilized in silk friboin-alginate spheres. Thus, the en
- Ferreira, Irlon M.,Nishimura, Rodolfo H.V.,Souza, Ana B. Dos A.,Clososki, Giuliano C.,Yoshioka, Sergio A.,Porto, André L.M.
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supporting information
p. 5062 - 5065
(2015/01/09)
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- Asymmetric transfer hydrogenation of aromatic ketones catalyzed by new chiral C2-symmetric bis(sulfonyl) tetraaza ligands complexed with [Ru(η6-p-cymene)Cl2]2 in water
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In this report, a new series of C2-symmetric bis(sulfonyl) tetraaza ligands were synthesized from (1S,2S)-1,2-diarylethylenediamine analogues and tested in the asymmetric transfer hydrogenation (ATH) of aromatic ketones by complexing with [Ru(η6-p-cymene)Cl2]2 employing sodium formate as hydrogen source in neat water. A moderate to excellent conversion (~99.8 %) and overall satisfying enantioselectivity (~92.8 %) were obtained with varied electronic and steric effects of the substituents on ligands and substrates.
- Liu, Xungao,Zhang, Tian,Hu, Yingying,Shen, Liang
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p. 1289 - 1295
(2014/07/21)
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- Genomic mining-based identification of novel stereospecific aldo-keto reductases toolbox from Candida parapsilosis for highly enantioselective reduction of carbonyl compounds
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Biocatalytic reduction of prochiral ketones offers significant potential in synthesis of optically active alcohols. However, so far the application of aldo-keto reductases (AKRs) in asymmetric reduction has been hampered due to limited availability of AKRs with high enantioselectivity and catalytic efficiency. Based on the genome sequence of Candida parapsilosis, a versatile bioresource for asymmetric reduction, eight open reading frames encoding putative AKRs were discovered and expressed, and the resulted enzymes (CPARs), comprising an AKR toolbox, were evaluated toward various carbonyl substrates. The CPARs were active to the selected substrates, especially 2-hydroxyacetophenone and ethyl 4-chloro-3-oxobutyrate. Additionally, most of them were obviously enantioselective to the substrates and gave alcohol products with optical purity up to 99%e.e. Of the enzymes, CPAR4 was outstanding with excellent enantioselectivity and broad substrate spectrum. All these positive features demonstrate that genomic mining is powerful in searching for novel and efficient biocatalysts of desired reactions for pharmaceuticals and fine chemicals synthesis.
- Guo, Rongyun,Nie, Yao,Mu, Xiao Qing,Xu, Yan,Xiao, Rong
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- Synthesis and catalytic applications of an extended range of tethered ruthenium(II)/η6-arene/diamine complexes
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A series of novel enantiopure Ru(II) complexes containing a chiral diamine and η6-arene connected by a tethering group have been prepared and were evaluated in the asymmetric reductions of a range of ketones. Changes to the level of steric hindrance and the addition of an electron-withdrawing functionality on the sulfonyl group have a significant effect on the reactivity and enantioselectivity of the catalysts.
- Hodgkinson, Roy,Jurk, Vclav,Zanotti-Gerosa, Antonio,Nedden, Hans Günter,Blackaby, Andrew,Clarkson, Guy J.,Wills, Martin
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supporting information
p. 5517 - 5524
(2015/02/19)
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- Synthesis of chiral 2-(anilinophenylmethyl)pyrrolidines and 2-(anilinodiphenylmethyl)pyrrolidine and their application to enantioselective borane reduction of prochiral ketones as chiral catalysts
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Chiral diamines, 2-(anilinophenylmethyl)pyrrolidines and 2-(anilinodiphenylmethyl)pyrrolidine, were prepared from N-(tert-butoxycarbonyl) pyrrolidine or (S)-proline as a starting material, respectively. These chiral diamines were efficient for the catalytic enantioselective borane reduction of acetophenone. Using (S)-2-(anilinodiphenylmethyl)pyrrolidine, chiral secondary alcohols were obtained from prochiral ketones with good to excellent enantiomeric excesses (up to 98% ee).
- Hosoda, Naoya,Kamito, Hideaki,Takano, Miki,Takebe, Yoshitaka,Yamaguchi, Yoshitaka,Asami, Masatoshi
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p. 1739 - 1746
(2013/03/13)
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- Preparative access to medicinal chemistry related chiral alcohols using carbonyl reductase technology
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Libraries of highly enantioenriched secondary alcohols in both enantiomeric forms were synthesised by enzymatic reduction of their parent ketones using selectAZyme carbonyl reductase (CRED) technology. Commercially available CREDs were able to reduce a range of substrate classes efficiently and with very high enantioselectivity. Matching substrate classes to small subsets of CREDs enabled the fast development of preparative bioreductions and the rapid generation of 100-1500 mg samples of chiral alcohols in typically >95% ee and the majority in ≥99.0% ee. The conditions for small scale synthesis were then scaled up to 0.5 kg to deliver one of the chiral alcohols, (S)-1-(4-bromophenyl)-2-chloroethanol, in 99.8% ee and 91% isolated yield.
- Rowan, Andrew S.,Moody, Thomas S.,Howard, Roger M.,Underwood, Toby J.,Miskelly, Iain R.,He, Yanan,Wang, Bo
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p. 1369 - 1381
(2013/12/04)
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- Highly enantioselective double reduction of phenylglyoxal to (R)-1-phenyl-1,2-ethanediol by one NADPH-dependent yeast carbonyl reductase with a broad substrate profile
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The activity and enantioselectivity of a carbonyl reductase from Pichia pastoris GS115 were evaluated with a series of carbonyl compounds including aryl aldehydes, ketones, α- and β-ketoesters. This recombinant enzyme possessed a broad substrate profile with the ability of reducing both aldehydes and ketones. Especially, the enzyme catalyzed the double reduction of phenylglyoxal to (R)-1-phenyl-1,2-ethanediol with 99% yield and 99% ee by coupling with d-glucose dehydrogenase for the regeneration of cofactor NADPH, representing the first example of effective reduction of both aldehyde and ketone functional groups in one molecule by using only one enzyme. Furthermore, this study provides valuable information for guiding the future application of this versatile biocatalyst.
- Li, Zhe,Liu, Weidong,Chen, Xi,Jia, Shiru,Wu, Qiaqiang,Zhu, Dunming,Ma, Yanhe
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p. 3561 - 3564
(2013/04/24)
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- Multi-enzymatic biosynthesis of chiral β-hydroxy nitriles through co-expression of oxidoreductase and halohydrin dehalogenase
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To establish a system for the efficient one bacterial multi-enzymatic biosynthesis of both (R)- and (S)-β-hydroxy nitriles, we co-expressed alcohol dehydrogenases with opposite stereoselectivities, cofactor regeneration enzymes, and a halohydrin dehalogenase in Escherichia coli. By researching cofactor recycling and various co-expression strategies and by selecting and engineering the halohydrin dehalogenase, we engineered two E. coli strains, which were subsequently used in a cascade of reactions to produce chiral β-hydroxy nitriles with high enantiomeric excess directly from prochiral α-halo ketones. Three valuable pharmaceutical intermediates were prepared by means of this catalytic system, and substrate conversion reached about >99%. More importantly, the system is of low cost because there is no need for expensive cofactors or for expression and purification of the component enzymes. Copyright
- Chen, Shao-Yun,Yang, Chen-Xi,Wu, Jian-Ping,Xu, Gang,Yang, Li-Rong
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p. 3179 - 3190
(2013/12/04)
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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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- Immobilization of marine fungi on silica gel, silica xerogel and chitosan for biocatalytic reduction of ketones
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The scanning electron microscopy (SEM) analysis showed that whole living hyphal of marine fungi Aspergillus sclerotiorum CBMAI 849 and Penicillium citrinum CBMAI 1186 were immobilized on support matrices of silica gel, silica xerogel and/or chitosan. P. citrinum immobilized on chitosan catalyzed the quantitative reduction of 1-(4-methoxyphenyl)-ethanone (1) to the enantiomer (S)-1-(4-methoxyphenyl)-ethanol (3b), with excellent enantioselectivity (ee > 99%, yield = 95%). Interestingly, ketone 1 was reduced with moderate selectivity and conversion to alcohol 3b (ee = 69%, c 40%) by the free mycelium of P. citrinum. This free mycelium of P. citrinum catalyzed the production of the (R)-alcohol 3a, the antipode of the alcohol produced by the immobilized cells. P. citrinum immobilized on chitosan also catalyzed the bioreduction of 2-chloro-1-phenylethanone (2) to 2-chloro-1-phenylethanol (4a,b), but in this case without optical selectivity. These results showed that biocatalytic reduction of ketones by immobilization hyphal of marine fungi depends on the xenobiotic substrate and the support matrix used.
- Rocha, Lenilson Coutinho,De Souza, Adriano Lopes,Rodrigues Filho, Ubirajara Pereira,Campana Filho, Sergio Paulo,Sette, Lara Duraes,Porto, Andre Luiz Meleiro
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p. 160 - 165
(2012/11/06)
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- Efficient synthesis of (R)-2-chloro-1-(3-chlorophenyl)ethanol by permeabilized whole cells of candida ontarioensis
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(R)-2-Chloro-1-(3-chlorophenyl)ethanol is a key pharmaceutical intermediate in the synthesis of β3-adrenoceptor receptor (β;3-AR) agonists. The asymmetric reduction of 2-chloro-1-(3-chlorophenyl)ethanone to (R)-2-chloro-1-(3-chlorophenyl)ethanol catalyzed by resting cells of Candida ontarioensis was studied. At a substrate concentration of 10 g/L, the microbial cells showed excellent catalytic activity under the optimum reaction conditions, giving the product in 99.9% ee and 99.0% yield. After cetyltrimethylammonium bromide-pretreatment, the activity of permeabilized Candida ontarioensis cells was increased by more than 2-fold and the product could be produced over the significantly shortened reaction period of 24 h in 99.9% ee and 97.5%yield at a substrate concentration of 30 g/L. This work provides a practical approach for the efficient preparation of the important chiral intermediate (R)-2-chloro-1-(3-chlorophenyl) ethanol.
- Ni, Ye,Zhang, Beihua,Sun, Zhihao
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scheme or table
p. 681 - 687
(2012/08/08)
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- Preparation of microgel-supported chiral catalysts and their application in the asymmetric hydrogenation of aromatic ketones
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An enantiomerically pure chiral monomer (S,S)-2 was prepared and copolymerized with styrene and four different cross-linkers to produce four distinct microgel-supported chiral TsDPEN derivatives. These chiral copolymers were allowed to form complexes with
- Deng, Jia,Lu, Cuifen,Yang, Guichun,Chen, Zuxing
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experimental part
p. 378 - 382
(2012/08/13)
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- Chiral epoxides via borane reduction of 2-haloketones catalyzed by spiroborate ester: Application to the synthesis of optically pure 1,2-hydroxy ethers and 1,2-azido alcohols
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An enantioselective borane-mediated reduction of a variety of 2-haloketones with 10% spiroaminoborate ester 1 as catalyst is described. By a simple basic workup of 2-halohydrins, optically active epoxides are obtained in high yield and with excellent enantiopurity (up to 99% ee). Ring-opening of oxiranes with phenoxides or sodium azide is investigated under different reaction conditions affording nonracemic 1,2-hydroxy ethers and 1,2-azido alcohols with excellent enantioselectivity (99% ee) and in good to high chemical yield. 2011 American Chemical Society.
- Huang, Kun,Wang, Haiyang,Stepanenko, Viatcheslav,De Jesus, Melvin,Torruellas, Carilyn,Correa, Wildeliz,Ortiz-Marciales, Margarita
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supporting information; experimental part
p. 1883 - 1886
(2011/06/20)
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- Efficient reduction of ethyl 2-oxo-4-phenylbutyrate at 620 ?l -1 by a bacterial reductase with broad substrate spectrum
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A β-ketoacyl-ACP reductase (FabG) gene from Bacillus sp. ECU0013 was heterologously overexpressed in Escherichia coli and the encoded protein was purified to homogeneity. The recombinant reductase could reduce a broad spectrum of prochiral ketones including aromatic ketones and keto esters and showed the highest activity in the asymmetric reduction of ethyl 2-oxo-4-phenylbutyrate (OPBE). Using E. coli cells coexpressing both FabG and glucose dehydrogenase (GDH) genes, as much as 620 ?L-1 of OPBE was almost stoichiometrically converted to ethyl (S)-2-hydroxy-4-phenylbutyrate [(S)-HPBE] with excellent (>99%) enantiomeric excess. More importantly, the process could be performed smoothly without external addition of an expensive cofactor as usually done and could be scaled up very easily. All these positive features demonstrate the applicability of this reductase for the large-scale production of optically active α-hydroxy acids/esters.
- Ni, Yan,Li, Chun-Xiu,Zhang, Jie,Shen, Nai-Dong,Bornscheuer, Uwe T.,Xu, Jian-He
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supporting information; experimental part
p. 1213 - 1217
(2011/07/09)
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- Asymmetric transfer hydrogenation of prochiral ketones in aqueous media with chiral water-soluble and heterogenized bifunctional catalysts of the RhCp*-type ligand
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Asymmetric transfer hydrogenation (ATH) of prochiral aromatic ketones was carried out with a water-soluble complex of RhIIICp* and mononitrobenzenesulfonamide bidentate ligand (1R,2R)-N-(2-aminocyclohexyl)-4- nitrobenzenesulfonamide 1 derived from chiral cyclohexane-1,2-diamine. Aqueous sodium formate was used as the hydride source. The reaction afforded the chiral alcohols in good enantioselectivities (79-93%) and yields (>99%). The modified monosulfonamide ligand was also covalently immobilized on solid phase such as silica, resin, and mesoporous SBA-15 silica and then explored as a catalyst with RhIIICp* in the ATH of acetophenone. Copyright
- Barron-Jaime, Angelica,Narvaez-Garayzar, Oscar F.,Gonzalez, Jorge,Ibarra-Galvan, Valentin,Aguirre, Gerardo,Parra-Hake, Miguel,Chavez, Daniel,Somanathan, Ratnasamy
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experimental part
p. 178 - 184
(2011/11/06)
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- Application of proline-functionalised 1,2-diphenylethane-1,2-diamine (DPEN) in asymmetric transfer hydrogenation of ketones
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A series of enantiomerically pure ligands containing a combination of proline and DPEN groups have been prepared and employed in the asymmetric transfer hydrogenation of ketones. In the case of cyclic ketones, alcohols with ee values of up to 98% were obtained.
- Manville, Charles V.,Docherty, Gordon,Padda, Ranbir,Wills, Martin
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experimental part
p. 6893 - 6901
(2012/01/06)
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- MPV reduction using AlIII-calix[4]arene Lewis acid catalysts: Molecular-level insight into effect of ketone binding
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Catalytic Meerwein-Ponndorf-Verley (MPV) reduction using Al III-calix[4]arene complexes is investigated as a model system that requires the bringing together of two different chemical species, ketone and alkoxide, within a six-membered transition state. Two-point versus one-point ketone binding is demonstrated to be the most salient feature that controls MPV catalysis rate. A 7.7-fold increase in rate is observed when comparing reactants consisting of a bidentate Cl-containing ketone and sterically and electronically similar but looser-binding ketones, which are substituted with H and F. The one-point and two-point nature of ketone binding for the various ketones investigated is independently assessed using a combination of structural data derived from single-crystal X-ray diffraction and DFT-based molecular modeling. Using MPV catalysis with inherently chiral calix[4]arenes, the effect of multiple point reactant binding on enantioselectivity is elucidated. A higher denticity of ketone binding appears to increase the sensitivity of the interplay between chiral active site structure and MPV reduction enantioselectivity.
- Nandi, Partha,Matvieiev, Yuriy I.,Boyko, Vyacheslav I.,Durkin, Kathleen A.,Kalchenko, Vitaly I.,Katz, Alexander
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experimental part
p. 42 - 49
(2011/12/13)
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- Asymmetric transfer hydrogenation of prochiral ketones catalyzed by aminosulfonamide-ruthenium complexes in ionic liquid
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Chiral aminosulfonamides containing imidazolium group were used as ligands for the ruthenium(II)-catalyzed asymmetric transfer hydrogenation of prochiral ketones in ionic liquid, affording good to excellent conversions and enantiomeric excesses. The catalytic system could be easily recovered and reused several times. Versita Sp. z o.o.
- Zhou, Zhongqiang,Sun, Yong,Zhang, Aiqing
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experimental part
p. 175 - 179
(2012/04/04)
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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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- Candida tropicalis CE017: A new Brazilian enzymatic source for the bioreduction of aromatic prochiral ketones
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The reactivity and stereoselectivity showed by a new strain of Candida tropicalis in the reduction of prochiral ketones have been compared with the ones previously attained in our laboratory using microorganisms from the Brazilian biodiversity. In this manner, Candida tropicalis has demonstrated its versatility as stereoselective agent in the bioreduction of a series of aromatic ketones. These prochiral compounds were converted into their corresponding optically alcohols with moderate to excellent stereopreference depending on the substrate structure. Among ketones tested, nitroacetophenones were enzymatically reduced to enantiopure (S)-alcohol with complete conversion.
- Vieira, Gizelle A. B.,De Freitas Araujo, Daniel M.,Lemos, Telma L. G.,De Mattos, Marcos Carlos,Da Conceic?a?o F. De Oliveira, Maria,Melo, Va?nia M. M.,De Gonzalo, Gonzalo,Gotor-Ferna?ndez, Vicente,Gotor, Vicente
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experimental part
p. 1509 - 1516
(2010/11/04)
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