- Enantioselective biocatalytic reduction of non-protected hydroxyacetophenones
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Direct enantioselective reduction of -, - and -hydroxyacetophenone without protection of the hydroxy moiety was carried out in the presence of (R)- and (S)-alcohol dehydrogenases as bio-catalysts. Whereas reduction of -hydroxyacetophenone gave only low to
- Neupert, Adrian,Ress, Tina,Wittmann, Jrgen,Hummel, Werner,Grger, Harald
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- Bioactive constituents from the rhizomes of Dioscorea septemloba Thunb
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Eight new compounds, dioscorosides G (1), H1 (2), H2 (3), dioscorol B (4), dioscorosides I (5), J (6), K1 (7), and K2 (8), together with twelve known ones (9–20) were obtained from the rhizomes of Dioscorea sept
- Zhang, Yi,Chao, Liping,Ruan, Jingya,Zheng, Chang,Yu, Haiyang,Qu, Lu,Han, Lifeng,Wang, Tao
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- Synthesis of (S)-1-(4-hydroxyphenyl)alcohols by eugenol dehydrogenase from Pseudomonas fluorescens E118
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(S)-1-(4-Hydroxyphenyl)ethanol and (S)-1-(4-hydroxyphenyl)propanol were synthesized with enantiomeric excesses of 96.6% and 95.2%, respectively, from the corresponding 4-alkylphenols by eugenol dehydrogenase from Pseudomonas fluorescens E118. The enantios
- Wieser, Marco,Furukawa, Hirotaka,Morita, Hiroshi,Yoshida, Toyokazu,Nagasawa, Toru
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- Synthesis and characterization of novel silica coated magnetic nanoparticles with tags of β-cyclodextrin: application as an eco-friendly and chiral micro-vessel catalyst in the enantioselective reduction of ketones
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In this work, we report the synthesis of a novel, green and recoverable organic–inorganic magnetic nanocomposite by grafting β-cyclodextrin on the surface of a silica-coated magnetic nanoparticle, Fe3O4@SiO2/Pr-β-CD. FT-IR spectroscopy, transmission electron microscopy, CHN analysis, thermogravimetric analysis, vibrating sample magnetometer and X-ray diffraction analyses confirmed its structure. The magnetic core–shell structured modified silica microsphere has been successfully used as a chiral micro-vessel catalyst for the enantioselective reduction of ketones by NaBH4. The described catalyst was regenerated and reused without any significant changes in the yield and enantiomeric excess.
- Jafari Nasab, Mina,Kiasat, Ali Reza
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- The reaction mechanism of chiral hydroxylation of p -OH and p -NH 2 substituted compounds by ethylbenzene dehydrogenase
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Ethylbenzene dehydrogenase (EbDH; enzyme commission (EC) number: 1.17.99.2) is a unique biocatalyst that hydroxylates alkylaromatic and alkylheterocyclic compounds to (S)-secondary alcohols under anaerobic conditions. The enzyme exhibits a high promiscuity catalyzing oxidation of over 30 substrates, inter alia, para-substituted alkylphenols and alkylanilines. Secondary alcohols with OH and NH2 substituents in the aromatic ring are highly valuable synthons for many biologically active compounds in the fine chemical industry. EbDH hydroxylates most of the studied compounds highly enantioselectively, except for five substrates that harbour OH and NH2 groups in the para position, which exhibit a significant decrease in the percent enantiomeric excess (% ee). This phenomenon is inconsistent with the previously suggested enzyme mechanism, but it may be linked to a stabilization of the carbocation intermediate by deprotonation of the OH or NH2 substituent in the active site that yields a transient quinone (imine) ethide species. This would initiate an alternative reaction pathway involving the addition of a water molecule to a C=C double bond. This hypothesis was cross-validated by density functional theory (DFT) cluster modelling of the alternative reaction pathway with 4-ethylphenol, as well as by experimental assessment of the pH dependency of enantiomeric excesses. The results reported herein suggest that the alternative reaction pathway may significantly contribute to the overall reaction if the carbocation intermediates are stabilized by deprotonation.
- Dudzik, Agnieszka,Kozik, Bartlomiej,Tataruch, Mateusz,Wojcik, Anna,Knack, Daniel,Borowski, Tomasz,Heider, Johann,Witko, Malgorzata,Szaleniec, MacIej
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- A Rational Active-Site Redesign Converts a Decarboxylase into a C=C Hydratase: "tethered Acetate" Supports Enantioselective Hydration of 4-Hydroxystyrenes
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The promiscuous regio- and stereoselective hydration of 4-hydroxystyrenes catalyzed by ferulic acid decarboxylase from Enterobacter sp. (FDC-Es) depends on bicarbonate bound in the active site, which serves as a proton relay activating a water molecule fo
- Payer, Stefan E.,Pollak, Hannah,Glueck, Silvia M.,Faber, Kurt
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- An Enantioconvergent Benzylic Hydroxylation Using a Chiral Aryl Iodide in a Dual Activation Mode
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The application of a triazole-substituted chiral iodoarene in a direct enantioselective hydroxylation of alkyl arenes is reported. This method allows the rapid synthesis of chiral benzyl alcohols in high yields and stereocontrol, despite its nontemplated nature. In a cascade activation consisting of an initial irradiation-induced radical C-H-bromination and a consecutive enantioconvergent hydroxylation, the iodoarene catalyst has a dual role. It initiates the radical bromination in its oxidized state through an in-situ-formed bromoiodane and in the second, Cu-catalyzed step, it acts as a chiral ligand. This work demonstrates the ability of a chiral aryl iodide catalyst acting both as an oxidant and as a chiral ligand in a highly enantioselective C-H-activating transformation. Furthermore, this concept presents an enantioconvergent hydroxylation with high selectivity using a synthetic catalyst.
- Abazid, Ayham H.,Clamor, Nils,Nachtsheim, Boris J.
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p. 8042 - 8048
(2020/09/21)
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- Deracemization of sec-alcohols through sequential application of C. Albicans and Ketoreductases
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A biocatalytic cascade process was developed using immobilized cells of the wild type yeast Candida albicans CCT 0776 in calcium alginate beads and a commercially available ketoreductase. The aim was to promote deracemization by stereoinversion of (±)-1-arylethanols in high substrate concentration (above 100 mmol L-1) to prepare the (R)-enantiomers of the alcohols (90-99percent), with a high enantiomeric excess (83-99percent) after 2 to 19 h. The (R)-1-(3-methoxyphenyl)ethanol, with 70percent yield and 91percent ee, obtained after 5 h was used to prepare (S)-1-(3-methoxyphenyl)-ethylamine with 60percent yield and 91percent ee after two steps, a key intermediate in the synthesis of (S)-rivastigmine.
- Nasário, Fábio D.,Moran, Paulo J.S.,Rodrigues, José Augusto R.
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p. 772 - 779
(2019/08/26)
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- Multienzyme One-Pot Cascade for the Stereoselective Hydroxyethyl Functionalization of Substituted Phenols
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The operability and substrate scope of a redesigned vinylphenol hydratase as a single biocatalyst or as part of multienzyme cascades using either substituted coumaric acids or phenols as stable, cheap, and readily available substrates are reported.
- Payer, Stefan E.,Pollak, Hannah,Schmidbauer, Benjamin,Hamm, Florian,Juri?i?, Filip,Faber, Kurt,Glueck, Silvia M.
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supporting information
p. 5139 - 5143
(2018/09/13)
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- Multigram Scale Enzymatic Synthesis of (R)-1-(4′-Hydroxyphenyl)ethanol Using Vanillyl Alcohol Oxidase
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The enantioselective oxyfunctionalisation of C?H bonds is a highly interesting reaction, as it provides access to chiral alcohols that are important pharmaceutical building blocks. However, it is hard to achieve using traditional methods. One way in which it can be achieved is through the action of oxidative enzymes. Although many reports of the oxyfunctionalisation capabilities of enzymes at an analytical scale have been published, reports on the use of enzymes to achieve oxyfunctionalisation on a synthetically relevant scale are fewer. Here, we describe the scale-up of the conversion of 4-ethylphenol to (R)-1-(4′-hydroxyphenyl)ethanol using the flavin-dependent enzyme vanillyl alcohol oxidase. The process was optimised by testing different reaction media and substrate and enzyme concentrations and by performing it under an oxygen atmosphere. Under optimised reaction conditions, 4.10 g (R)-1-(4′-hydroxyphenyl)ethanol at 97% ee was obtained from 10 g 4-ethylphenol (isolated yield 36%). These results highlight some of the challenges that can be encountered during scale-up of an enzymatic oxyfunctionalisation process to a synthetically relevant scale and will be of use for the development of enzymatic processes for the synthesis of industrially relevant compounds. (Figure presented.).
- Ewing, Tom A.,Kühn, Jasmin,Segarra, Silvia,Tortajada, Marta,Zuhse, Ralf,van Berkel, Willem J. H.
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supporting information
p. 2370 - 2376
(2018/06/20)
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- Deracemization of 1-phenylethanol via tandem biocatalytic oxidation and reduction
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(R)-1-Arylethanols and other secondary alcohols were prepared at high ee (>90%) by oxidative kinetic resolution using resting cells of the yeast Candida albicans CCT 0776. The deracemization process of 1-phenylethanol 1a catalyzed by the yeast was elucidated by studying each step separately. It was determined that the reaction occurred via cyclic deracemization, to give (R)-1a in 89% yield and with 98% ee. Finally, deracemization by stereoinversion of rac-1a was studied using a tandem process of C. albicans followed by Lactobacillus brevis CCT 3745. Inverting the sequence of these microorganisms produced an enantiomerically pure antipode.
- Nasário, Fábio D.,Cazetta, Tarcila,Moran, Paulo J.S.,Rodrigues, J. Augusto R.
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p. 404 - 409
(2016/05/19)
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- Hydroxy functionalization of non-activated Ci-H and Ci=C Bonds: New perspectives for the synthesis of alcohols through biocatalytic processes
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New perspectives through enzymes: Recent breakthroughs have been achieved in the selective hydroxy functionalization of non-activated Ci-H and Ci=C bonds. Enzymes turned out to be suitable catalysts for the ω-hydroxylation of (substituted) alkanes and regioselective hydroxylation of aromatic hydrocarbons with atmospheric oxygen as the oxidant, and the asymmetric addition of water to non-activated alkenes.
- Groeger, Harald
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p. 3067 - 3069
(2014/04/03)
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- Asymmetric enzymatic hydration of hydroxystyrene derivatives
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More than one activity: Owing to their hydratase activity, phenolic acid decarboxylases catalyze the regio- and stereoselective addition of H 2O across the C=C double bond of hydroxystyrene derivatives yielding (S)-4-(1-hydroxyethyl)phenols with up to 82 % conversion and 71 % ee. Based on structure analysis and molecular docking simulations, a catalytic mechanism for this novel enzymatic reaction is proposed. Copyright
- Wuensch, Christiane,Gross, Johannes,Steinkellner, Georg,Gruber, Karl,Glueck, Silvia M.,Faber, Kurt
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supporting information
p. 2293 - 2297
(2013/04/10)
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- Facile access to chiral alcohols with pharmaceutical relevance using a ketoreductase newly mined from Pichia guilliermondii
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Chiral secondary alcohols with additional functional groups are frequently required as important and valuable synthons for pharmaceuticals, agricultural and other fine chemicals. With the advantages of environmentally benign reaction conditions, broad reaction scope, and high stereoselectivity, biocatalytic reduction of prochiral ketones offers significant potential in the synthesis of optically active alcohols. A CmCR homologous carbonyl reductase from Pichia guilliermondii NRRL Y-324 was successfully overexpressed. Substrate profile characterization revealed its broad substrate specificity, covering aryl ketones, aliphatic ketones and ketoesters. Furthermore, a variety of ketone substrates were asymmetrically reduced by the purified enzyme with an additionally NADPH regeneration system. The reduction system exhibited excellent enantioselectivity (>99% ee) in the reduction of all the aromatic ketones and ketoesters, except for 2-bromoacetophenone (93.5% ee). Semi-preparative reduction of six ketones was achieved with high enantioselectivity (>99% ee) and isolation yields (>80%) within 12 h. This study provides a useful guidance for further application of this enzyme in the asymmetric synthesis of chiral alcohol enantiomers. Copyright
- Xu, Guochao,Yu, Huilei,Xu, Jianhe
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p. 349 - 354
(2013/08/22)
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- Immobilization of a modified tethered rhodium(III)-p-toluenesulfonyl-1,2- diphenylethylenediamine catalyst on soluble and solid polymeric supports and successful application to asymmetric transfer hydrogenation of ketones
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Catalyst immobilization through covalent attachment onto a support is one strategy to provide recyclable systems. Here, soluble and surface-functionalized solid polymers were used as supports for a modified tethered rhodium(III)-p-toluenesulfonyl-1,2-diphenylethylenediamine [Rh(III)-TsDPEN] complex. The supported catalysts were applied to the asymmetric transfer hydrogenation of phenyl ketones in aqueous solution of sodium formate. High ee values (up to 99%) and good activities were achieved. It was discovered that the solid polymer-supported catalyst could be recycled at least four times without a significant decrease of the activity when a mixture of sodium formate and formic acid was used as the hydrogen source. This catalytic system provides a promising approach towards an ecologically and economically rational production of enantioenriched building blocks.
- Dimroth, Jonas,Keilitz, Juliane,Schedler, Uwe,Schomaecker, Reinhard,Haag, Rainer
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supporting information; scheme or table
p. 2497 - 2506
(2011/02/23)
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- Immobilized Manihot esculenta preparation as a novel biocatalyst in the enantioselective acetylation of racemic alcohols
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The enzymatic preparation obtained from a discard of Manihot esculenta roots has been successfully immobilized on calcium alginate hydrogels. This preparation has been tested as a chiral biocatalyst in the enzymatic acylation of a set of racemic aromatic alcohols. Depending on the reaction conditions, excellent enantioselectivities can be achieved. Some parameters that can alter the biocatalytic properties of the enzyme, such as solvent, temperature, acyl donor and substrate structure have been studied exhaustively in order to establish a deeper knowledge of this novel biocatalyst.
- Machado, Luciana L.,Lemos, Telma L.G.,de Mattos, Marcos Carlos,de Oliveira, Maria da Conceicao F.,de Gonzalo, Gonzalo,Gotor-Fernandez, Vicente,Gotor, Vicente
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p. 1418 - 1423
(2008/12/20)
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- Biocatalytic asymmetric hydrogen transfer employing Rhodococcus ruber DSM 44541
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Nonracemic sec-alcohols of opposite absolute configuration were obtained either by asymmetric reduction of the corresponding ketone using 2-propanol as hydrogen donor or by enantioselective oxidation through kinetic resolution of the rac-alcohol using acetone as hydrogen acceptor employing whole lyophilized cells of Rhodococcus ruber DSM 44541. The microbial oxidation/reduction system exhibits not only excellent stereo- and enantioselectivity but also a broad substrate spectrum. Due to the exceptional tolerance of the biocatalyst toward elevated concentrations of organic materials (solvents, substrates and cosubstrates), the process is highly efficient. The simple preparation of the biocatalyst and its ease of handling turns this system into a versatile tool for organic synthesis.
- Stampfer, Wolfgang,Kosjek, Birgit,Faber, Kurt,Kroutil, Wolfgang
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p. 402 - 406
(2007/10/03)
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- Biocatalytic oxidation of 4-vinylphenol by Nocardia
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Nocardia species NRRL 5646 stereospecifically hydrates 4-vinylphenol (15) to S-1-(4′-hydroxyphenyl)ethanol (17), and further oxidizes 17 to 4′-hydroxyacetophenone (18). Labeled metabolites 17 and 18 obtained from incubations in D2O and H218O support initial enzymatic tautomerization of 15 to a reactive quinone methide (16), which adds water in the first reaction. Commitment to catalysis is high in the hydration reaction, while the alcohol dehydrogenation reaction appears to be reversible. The stereochemical features of water addition, alcohol oxidations, and ketone reductions with growing culture biocatalysis were established by chiral HPLC. Alcohol oxidations or ketone reductions in 12 000 × g supernatants preferentially require NADP+-NADPH,H+ as co-factors. The alcohol dehydrogenase has broad substrate specificity, favoring the oxidation of primary alkanols and 4-hydroxybenzyl alcohols.
- Lee, Kyung-Seon,Rosazza, John P.N.
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p. 582 - 588
(2007/10/03)
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- Efficient enantioselective reduction of ketones with Daucus carota root
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A novel and efficient reduction of various prochiral ketones such as acetopehones, α-azido aryl ketones, β-ketoesters, and aliphatic acyclic and cyclic ketones to the corresponding optically acive secondary alcohols with moderate to excellent chemical yield was achieved by using Daucus carota, root plant cells under extremely mild and environmentally benign conditions in aqueous medium, has been described. Many of these optically active alcohols are the potential chiral building blocks for the synthesis of pharmaceutically important molecules and asymmetric chiral ligands. Hence, this biocatalytic approach is found to be the most suitable for the preparation of a wide range of chiral alcohols and gave inspiration for the development of a new biotechnological process.
- Yadav,Nanda,Thirupathi Reddy,Bhaskar Rao
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p. 3900 - 3903
(2007/10/03)
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- Liquid crystal compounds having chiral ester head groups
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Liquid crystal compounds which show a ferroelectric phase and which exhibit high spontaneous polarization values and smectic behavior over a range of temperatures have the formula STR1 wherein R1 is alkyl of from 1 to 16 carbon atoms; alkoxy; haloalkyl; alkoxyalkyl, wherein the alkoxy substituent thereof comprises a chain of carbon atoms including one or more oxygen ether atoms; or alkoxyalkoxy, wherein the alkoxy substituent thereof comprises a chain of carbon atoms including one or more oxygen ether atoms; R2 is alkyl of from 1 to 4 carbon atoms; each of R3 and R4 is alkylene; n is an integer 1 or 2; and W is alkyl of from 1 to 12 carbon atoms or fluoroalkyl of the formula STR2 wherein each of X, Y and Z is hydrogen or fluorine, m is zero or an integer from 1 to 6, and at least one of X, Y and Z is fluorine when m is zero.
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- A Facile General Route to Enantiomeric 1-(4-Hydroxyphenyl)alkanols, and an Improved Synthesis of 4-Vinylphenol
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Optically pure 1-(4-hydroxyphenyl)alkanols, the phenolic hydroxy groups of which are protected, have been obtained by an improved resolution procedure.Since subsequent deprotection of these is accompanied by complete elimination to the phenolic styrenes, an efficient synthesis of 4-vinylphenol from the racemic protected alcohols by simultaneous deprotection and elimination at 0 deg C has been developed. The target chiral 1-(4-hydroxyphenyl)alkanols have been prepared by treatment of the O-protected 4-hydroxyphenyl alkyl ketone with the enantiomers of chlorodiisopinocampheylborane at 0 deg C, when asymmetric reduction and simultaneous deprotection gives the enantiomeric diols in >99.7percent e.e. and high chemical yield.
- Everhart, E. Thomas,Craig, J. Cymerman
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p. 1701 - 1707
(2007/10/02)
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