- Application of robust ketoreductase from Hansenula polymorpha for the reduction of carbonyl compounds
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Enzyme-catalysed asymmetric reduction of ketones is an attractive tool for the production of chiral building blocks or precursors for the synthesis of bioactive compounds. Expression of robust ketoreductase (KRED) from Hansenula polymorpha was upscaled and applied for the asymmetric reduction of 31 prochiral carbonyl compounds (aliphatic and aromatic ketones, diketones and β-keto esters) to the corresponding optically pure hydroxy compounds. Biotransformations were performed with the purified recombinant KRED together with NADP+ recycling glucose dehydrogenase (GDH, Bacillus megaterium), both overexpressed in Escherichia coli BL21(DE3). Maximum activity of KRED for biotransformation of ethyl-2-methylacetoacetate achieved by the high cell density cultivation was 2499.7 ± 234 U g–1DCW and 8.47 ± 0.40 U·mg–1E, respectively. The KRED from Hansenula polymorpha is a very versatile enzyme with broad substrate specificity and high activity towards carbonyl substrates with various structural features. Among the 36 carbonyl substrates screened in this study, the KRED showed activity with 31, with high enantioselectivity in most cases. With several ketones, the Hansenula polymorpha KRED catalysed preferentially the formation of the (R)-secondary alcohols, which is highly valued.
- Petrovi?ová, Tatiana,Gyuranová, Dominika,Pl?, Michal,Myrtollari, Kamela,Smonou, Ioulia,Rebro?, Martin
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- A Colorimetric Method for Quantifying Cis and Trans Alkenes Using an Indicator Displacement Assay
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A colorimetric indicator displacement assay (IDA) amenable to high-throughput experimentation was developed to determine the percentage of cis and trans alkenes. Using 96-well plates two steps are performed: a reaction plate for dihydroxylation of the alkenes followed by an IDA screening plate consisting of an indicator and a boronic acid. The dihydroxylation generates either erythro or threo vicinal diols from cis or trans alkenes, depending upon their syn- or anti-addition mechanisms. Threo diols preferentially associate with the boronic acid due to the creation of more stable boronate esters, thus displacing the indicator to a greater extent. The generality of the protocol was demonstrated using seven sets of cis and trans alkenes. Blind mixtures of cis and trans alkenes were made, resulting in an average error of ±2 % in the percentage of cis or trans alkenes, and implementing E2 and Wittig reactions gave errors of ±3 %. Furthermore, we developed variants of the IDA for which the color may be tuned to optimize the response for the human eye.
- Valenzuela, Stephanie A.,Crory, Hannah S. N.,Yao, Chao-Yi,Howard, James R.,Saucedo, Gabriel,de Silva, A. Prasanna,Anslyn, Eric V.
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p. 13819 - 13823
(2021/05/17)
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- Highly efficient and recyclable chiral Pt nanoparticle catalyst for enantioselective hydrogenation of activated ketones
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Thermoregulated phase-separable chiral Pt nanoparticle catalyst exhibited excellent ee (>99%) in the enantioselective hydrogenation of activated ketones for preparing chiral α-hydroxy acetals and chiral 1,2-diols. More importantly, the chiral catalyst could be easily separated by phase separation and directly reused in the next cycle without any loss in catalytic activity and enantioselectivity, even in the gram-scale reaction. The leaching of Pt was under the detection limit of the instrument.
- Xue, Xiuru,Chen, Pu,Xu, Peng,Wang, Yanhua
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- Reactivity of the CH-bonds of 2-butanol in liquid-phase oxidation
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The kinetics of product accumulation is studied in the azodiisobutyronitrile-initiated oxidation of 2-butanol. The relative reactivity for all types of the CH-bonds of 2-butanol is determined for reactions with peroxyl radicals at 60°C. It is established that the hydroxyl functional group of 2-butanol activates the CHbond in position 2 (α) and deactivates CH-bonds in positions 1, 3 (β), and 4 (γ), compared to the corresponding CH-bonds of saturated hydrocarbons.
- Puchkov,Nepomnyashchikh, Yu. V.
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p. 2337 - 2343
(2017/11/09)
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- Gold-Nanoparticle-Catalyzed Silaboration of Oxetanes and Unactivated Epoxides
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Supported gold nanoparticles catalyze the unprecedented insertion of a silylborane into the C-O bond of oxetanes and unactivated epoxides, forming γ- or β-silyloxy boronates in good to excellent yields. In the silaboration process the boron moiety is acting as a nucleophile and the silyl as an electrophile. No external additives or ligands are required, while the catalytic system is recyclable and reusable.
- Vasilikogiannaki, Eleni,Louka, Anastasia,Stratakis, Manolis
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p. 3895 - 3902
(2016/12/22)
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- Catalytic hydrogenation of cyclic carbonates: A practical approach from CO2 and epoxides to methanol and diols
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As an economical, safe and renewable carbon resource, CO2 turns out to be an attractive C1 building block for making organic chemicals, materials, and carbohydrates.[1] From the viewpoint of synthetic chemistry,[2] the utilization of CO2 as a feedstock for the production of industrial products may be an option for the recycling of carbon.[3] On the other hand, the transformation of chemically stable CO2 represents a grand challenge in exploring new concepts and opportunities for the academic and industrial development of catalytic processes.[4] The catalytic hydrogenation of CO2 to produce liquid fuels such as formic acid (HCO 2H)[5] or methanol[6] is a promising solution to emerging global energy problems. Methanol, in particular, is not only one of the most versatile and popular chemical commodities in the world, with an estimated global demand of around 48 million metric tons in 2010, but is also considered as the key to weaning the world off oil in the future.[6e, f] Although the production of methanol has already been industrialized by the hydrogenation of CO with a copper/zinc-based heterogeneous catalyst at high temperatures (250-300°C) and high pressures (50-100 atm),[6e, 7] the development of a practical catalytic system for the hydrogenation of CO2 into methanol still remains a challenge, as high activation energy barriers have to be overcome for the cleavage of the C=O bonds of CO2, albeit with favorable thermodynamics.[8] Heterogeneous catalysis for the hydrogenation of CO 2 into CH3OH has been extensively investigated, and Cu/Zn-based multi-component catalyst was found to be highly selective with a long life, but under relatively harsh reaction conditions (250 °C, 50 atm).[3b, 6d] Therefore, the production of methanol from CO2 by direct hydrogenation under mild conditions is still a great challenge for both academia and industry.
- Han, Zhaobin,Rong, Liangce,Wu, Jiang,Zhang, Lei,Wang, Zheng,Ding, Kuiling
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supporting information
p. 13041 - 13045
(2013/03/13)
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- Direct proline-catalyzed asymmetric α-aminoxylation of aldehydes and ketones
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The direct proline-catalyzed asymmetric α-aminoxylation of aldehydes and ketones has been developed using nitrosobenzene as an oxygen source, affording α-anilinoxy-aldehydes and -ketones with excellent enantioselectivity. Reaction conditions have been optimized, and low temperature (-20 °C) was found to be a key for the successful α-aminoxylation of aldehydes, while slow addition of nitrosobenzene is essential for that of ketones. The scope of the reaction is presented.
- Hayashi, Yujiro,Yamaguchi, Junichiro,Sumiya, Tatsunobu,Hibino, Kazuhiro,Shoji, Mitsuru
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p. 5966 - 5973
(2007/10/03)
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- Chemoenzymatic preparation of (2S,3S)- and (2R,3R)-2,3-butanediols and their esters from mixtures of d,l- and meso-diols
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An efficient method of preparing the pure enantiomers of 2,3-butanediol from commercially available mixtures of the d,l- and meso-isomers was developed. It furnished (2S,3S)-2,3-butanediol with >99% e.e. and a >99.5/0.5 diastereomeric ratio and (2R,3R)-2,3-butanediol in 95% e.e. and >95/5 diastereomeric ratio.
- Liu, Rong,Hoegberg, Hans-Erik
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p. 771 - 778
(2007/10/03)
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- Asymmetric hydrosilylation of ketones using trans-chelating chiral peralkylbisphosphine ligands bearing primary alkyl substituents on phosphorus atoms
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Asymmetric hydrosilylation of simple ketones with diphenylsilane proceeded at -40 °C in the presence of a rhodium complex (0.001 - 0.01 molar amount) coordinated with a trans-chelating chiral bisphosphine ligand bearing linear alkyl substituents on the phosphorus atoms, (R,R)-(S,S)-Et-, Pr-, or BuTRAP, giving the corresponding optically active (S)- secondary alcohols with up to 97% ee. The asymmetric hydrosilylation using TRAP ligands with bulkier P-substituents resulted in much lower enantioselectivities. The EtTRAP-rhodium catalyst was also effective for asymmetric hydrosilylation of keto esters with a coordination site for a rhodium atom (up to 98% ee). Optically active symmetrical diols were obtained with up to 99% ee from the corresponding diketones via the asymmetric reduction using 2.5 molar amounts of diphenylsilane.
- Kuwano, Ryoichi,Sawamura, Masaya,Shirai, Junya,Takahashi, Masatoshi,Ito, Yoshihiko
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p. 485 - 496
(2007/10/03)
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- Diastereoselectivity in the reduction of acyclic carbonyl compounds with diisopropoxytitanium(III) tetrahydroborate
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Diisopropoxytitanium(III) tetrahydroborate, ((i)PrO)2TiBH4, formed in situ in dichloromethane from diisopropoxytitanium dichloride and benzyltriethylammonium tetrahydroborate (1:2) reduces α-hydroxyketones/1,2- diketones and β-hydroxyketones/1,3-diketones to the corresponding diols with high stereoselectivity. In the case of α-hydroxyketones and 1,2-diketones, the anti isomer is the major product while reduction of β-hydroxyketones and 1,3-diketones leads to the syn isomer as the major product.
- Ravikumar,Sinha, Surajit,Chandrasekaran
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p. 5841 - 5844
(2007/10/03)
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- An improved synthesis of chiral diols via the asymmetric catalytic hydrogenation of prochiral diones
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The rates of the asymmetric hydrogenation of prochiral diketones catalyzed by Ru(BINAP) catalysts were substantially accelerated in the presence of small amounts of a strong acid.
- Fan, Qing-Hua,Yeung, Chi-Hung,Chan, Albert S. C.
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p. 4041 - 4045
(2007/10/03)
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- Resolution of Diols with C2-Symmetry by Lipase Catalysed Transesterification
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S-Ethyl thiooctanoate was used as acyl donor in the transesterification of 2,3-butanediol (1), 2,4-pentanediol (2), and 2,5-hexanediol (3), catalysed by a lipase from Candida antarctica.Mixtures of all stereoisomers were used as substrates in each case. 2,5-Hexanediol was transesterified with high stereoselectivity and the (2S,5S)-2,5-hexanediol was isolated in good yield with >99percent ee.The diester of (2R,5R)-2,5-hexanediol was formed in good yield and was hydrolysed to yield the (2R,5R)-2,5-hexanediol of high enantiomeric excess (>99percent ee).Similar results were obtainedfor 2,4-pentanediol with >99percent ee for both enantiomers.The stereoselectivity for 2,3-butanediol was lower than for 2 and 3, giving 89percent ee for the R,R-enantiomer and 34percent ee for the S,S-enantiomer.
- Mattson, Anders,Oehrner, Niklas,Hult, Karl,Norin, Torbjoern
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p. 925 - 930
(2007/10/02)
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- Stereoselectivity in the Hydride Reduction of Acyclic Diketones (1,2-, 1,3-, 1,4-, and 1,5-Induction)
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Diketones 2, 5, 9, and 19 as well as hemiketal 22 react with lithium aluminum hydride to give mixtures of d,l- and meso-diols.The stereochemical assignment of the diols can be obtained either by direct comparison with authentic samples (1,2-diols) or by NMR differentiation of diastereotopic groups (1,3- and 1,5-diols) or by stereospecific cyclization to the sila-heterocycles 12 and 13 (1,4-diols).The 1,2- and 1,4-diketones preferably produce meso-diols, whereas 1,3- and 1,5-diketones mostly lead to d,l-isomers.These alternating stereoselectivities can be explained by a stepwise reduction generating complexes of types 24 - 27 which are attacked by excess hydride via a diastereoface differentiating mode.
- Maier, Guenther,Roth, Cornelia,Schmitt, Reinhart K.
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p. 704 - 721
(2007/10/02)
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- SYNTHESIS BASED ON 2-BUTENE OXIDE.
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2-Butene oxide is likely in the very near future to become an important starting material for a number of large-scale synthesis. This article describes the preparation of saturated products by the catalytic reduction by hydrogen of 2-butene oxide to secondary butyl alcohol and conversion of the latter into methyl ethyl ketone. Also discussed is the preparation of unsaturated products by isomerization of 2-butene oxide to methylvinylcarbinol in presence of trilithium phosphate.
- Farberov,Bondarenko,Obukhov,Stepanova,Srednev,Vasil'eva
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p. 2385 - 2388
(2007/10/02)
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- PHOTOCHEMICAL REACTION OF ALCOHOLS-I IRRADIATION OF ALIPHATIC ALCOHOLS
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The UV irradiation of aliphatic alcohols gave α-glycols as the principal products.The values of the dl-α-glycol to meso-α-glycol ratios obtained in each example were analyzed.The stereochemical course of the formation of α-glycols, their conformations and configurations were established on basis of 1H NMR data.
- Balsells, R. Erra,Frasca, A. R.
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p. 245 - 255
(2007/10/02)
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- Gas-Phase Acid-Induced Nucleophilic Displacement Reactions. 5. Quantitative Evaluation of Neighboring-Group Participation in Bifunctional Compounds
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A previous radiolytic study on the stereochemistry of gas-phase nuclephilic displacement on several classes of positively charged intermediates, formed from the attack of gaseous acids (CH5+, C2H5+, CH3FCH3+, etc.) on suitable substrates, is now completed with the assessment of the detailed mechanism and the relative extent of the other major reaction pathways accompanying them.The analysis of the stereoisomeric distribution of the neutral end products allows a quantitative evaluation of the gas-phase neighboring-group participation in such systems.A participating-group ability trend of OH >> Br >/= Cl is found, which is appreciably dependent on the nature of the leaving group and the configuration of the starting substrate.The evaluation of the adjacent-group "effective concentration" in these gaseous systems provides the first direct evidence for a gas-phase anchimerically assisted ionic reaction, involving a three-membered ring formation.The results obtained in the gas phase differ significantly from those concerning related solvolytic processes.
- Angelini, Giancarlo,Speranza, Maurizio
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p. 3800 - 3806
(2007/10/02)
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- Gas-Phase Acid-Induced Nucleophilic Displacement Reactions. Stereochemistry of Inter- and Intramolecular Substitutions at Saturated Carbon
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The stereochemistry of gas-phase nucleophilic displacement by water on a number of positively charged intermediates was investigated under different experimental conditions.The ionic intermediates were generated in the gas phase at atmospheric pressure by attack of radiolytically formed Broensted (CH5+, C2H5+) and Lewis (C2H5+, CH3FCH3+) acids on selected mono- and bifunctional substrates.Isolation and identification of their neutral substituted products allowed us to demonstrate that, under the used experimental conditions, gas-phase acid-induced inter- and intramolecular nucleophilic displacement reactions occur via predominant (64-98percent) inversion of configuration at the reaction center.The yield and the stereoisomeric distribution of the substituted products were found to depend on either the nature of the gaseous acid used to generate the charged intermediates or the concentration of the added base (NH3 or H2O).Product distribution from bifunctional substrates is characterized by the presence of minor amounts of substituted derivatives retaining the original configuration of their neutral precursors.Their formation is ascribed to the occurence of an extensive neighboring group participation effect (an HO-3 process) on the displacement reaction, resulting in a double inversion of the reaction centers.A mechanistic model is proposed for gas-phase nucleophilic substitutions at atmospheric pressures, and compared with those from the related low-pressure ICR (ion cyclotrone resonance mass spectrometry) and solution-chemistry studies.
- Speranza, Maurizio,Angelini, Giancarlo
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p. 3115 - 3120
(2007/10/02)
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