- A one-step method for covalent bond immobilization of biomolecules on silica operated in aqueous solution
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A simple, one-step method for covalent bond immobilization of biomolecules on silica operated in water is described. In the approach, an NHS-ester linked methallylsilane is utilized as a bifunctional linker to couple the biomolecule to the silica surface. Weak organic acid such as acetic acid activates the silica surface enough to react with bifunctional linker without destroying activity of biomolecule.
- Sim, Yong-Kyun,Jung, Heetae,Kim, Su Hyun,Park, Jung-Woo,Park, Woo-Jin,Jun, Chul-Ho
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Read Online
- Discovery and Redesign of a Family VIII Carboxylesterase with High (S)-Selectivity toward Chiral sec-Alcohols
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Highly enantioselective lipase has been widely utilized in the preparation of versatile enantiopure chiral sec-alcohols through kinetic or dynamic kinetic resolution. Lipase is intrinsically (R)-selective, and it is difficult to obtain (S)-selective lipase. Recent crystal structures of a family VIII carboxylesterase have revealed that the spatial array of its catalytic triad is the mirror image of that of lipase but with a catalytic triad that is distinct from lipase. We, therefore, hypothesized that the family VIII carboxylesterase may exhibit (S)-enantioselectivity toward sec-alcohols similar to (S)-selective serine protease, whose catalytic triad is also spatially arrayed as its mirror image. In this study, a homologous enzyme (carboxylesterase from Proteobacteria bacterium SG_bin9, PBE) of a known family VIII carboxylesterase (pdb code: 4IVK) was prepared, which showed not only moderate (S)-selectivity toward sec-alcohols such as 3-butyn-2-ol and 1-phenylethyl alcohol but also (R)-selectivity toward particular sec-alcohols among the substrates explored. Furthermore, the (S)-selectivity of PBE has been significantly improved by rational redesign based on molecular modeling. Molecular modeling identified a binding pocket composed of Ser381, Ala383, and Arg408 for the methyl substituent of (R)-1-phenylethyl acetate and suggested that larger residues may increase the enantioselectivity by interfering with the binding of the slow-reacting enantiomer. As predicted, substituting Ser381with larger residues (Phe, Tyr, and Trp) significantly improved the (S)-selectivity of PBE toward all sec-alcohols explored, even the substrates toward which the wild-type PBE exhibits (R)-selectivity. For instance, the enantioselectivity toward 3-butyn-2-ol and 1-phenylethyl alcohol was improved from E = 5.5 and 36.1 to E = 2001 and 882, respectively, by single mutagenesis (S381F).
- Park, Areum,Park, Seongsoon
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p. 2397 - 2402
(2022/02/17)
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- Two Approaches for CAL-B-Catalyzed Enantioselective Deacylation of a Set of α-Phenyl Ethyl Esters: Organic Solvent with Sodium Carbonate and Micro-aqueous Medium
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Herein, we report an efficient enantioselective cleavage of the acyl- moiety of a set of α- phenyl ethyl esters with different chain-lengths catalyzed by lipase B from Candida antarctica (CAL-B) by comparing two reactional approaches: anhydrous media with sodium carbonates and micro-aqueous medium. The deacylation is performed in organic solvent, in the presence of Na2CO3 in the first case, and by addition of a drop of phosphate buffer solution pH 7 in the second. The results show the high efficiency of the deacylation in the presence of the sodium carbonate for the enzymatic resolution of all the esters and that in term of reactivity (31% ≤ conv ≤ 50%) and selectivity (E > 200). While, during the hydrolysis in micro-aqueous media, the conversion is strongly affected by the length of the acyl-chain side, the conversion decreases from conv = 50% with the 1-phenylethyl acetate 1a to conv = 19% with 1-phenyethyl dodecanoate 6a, and this, even if the selectivity remains high (E > 89). In both conditions, the lipase CAL-B shows a high enantioselectivities in favor of (R)-1-phenyl ethanol enantiomer (conv > 45%, E > 200) but the reactivity is modulated by the form and the size of the acyl-chain side. Graphic Abstract: [Figure not available: see fulltext.].
- Razi, Samra,Zeror, Saoussen,Merabet-Khelassi, Mounia,Kolodziej, Emilie,Toffano, Martial,Aribi-Zouioueche, Louisa
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p. 2603 - 2611
(2021/01/15)
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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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- Facile covalent bio-conjugation of hydroxyapatite
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Hydroxyapatite, which is a major component of the bone system in the human body, is an attractive material for bio-applications because it is nontoxic as well as biocompatible. In addition, many proteins are readily adsorbed on the surface of hydroxyapatite. The protein adsorption properties of hydroxyapatite have been employed for many bio-applications such as protein purification and nanomedical application. Nevertheless, the applications are not appropriate for proteins possessing hydrophobic surfaces because the surface of hydroxyapatite is charged. For applications with hydrophobic proteins, a covalent conjugation would be an alternative approach instead of physical adsorption. However, only a few examples of the covalent conjugation of proteins onto the surface of hydroxyapatite have been reported due to the lack of a convenient method for covalent conjugation. Herein, we report a facile process for the covalent conjugation of proteins on hydroxyapatite. We have successfully activated the surface of hydroxyapatite by a simple treatment with a peptide coupling reagent (for instance, N,N′-dicyclohexyl carbodiimide, N,N′-diisopropylcarbodiimide, or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide). Then, we directly conjugated enhanced green fluorescent protein (EGFP) as a model protein, and the conjugation was confirmed by a fluorescent microscope. We also employed the method for a hydrophobic surface protein, lipase. In this case, we found that a linker compound is required for the conjugation of lipase because of the distinct polarities of the surfaces of hydroxyapatite and lipase. The conjugated lipase on hydroxyapatite exhibited higher activity in organic solvents than the free form of lipase by a factor of up to 30 and can be recycled without a significant loss of the activity.
- Jeon, Minjeong,Jung, Suhyun,Park, Seongsoon
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p. 14870 - 14875
(2018/09/29)
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- Improved Enantioselectivity of Subtilisin Carlsberg towards Secondary Alcohols by Protein Engineering
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Generally, the catalytic activity of subtilisin Carlsberg (SC) for transacylation reactions with secondary alcohols in organic solvent is low. Enzyme immobilization and protein engineering was performed to improve the enantioselectivity of SC towards secondary alcohols. Possible amino-acid residues for mutagenesis were found by combining available literature data with molecular modeling. SC variants were created by site-directed mutagenesis and were evaluated for a model transacylation reaction containing 1-phenylethanol in THF. Variants showing high E values (>100) were found. However, the conversions were still low. A second mutation was made, and both the E values and conversions were increased. Relative to that shown by the wild type, the most successful variant, G165L/M221F, showed increased conversion (up to 36 %), enantioselectivity (E values up to 400), substrate scope, and stability in THF.
- Dorau, Robin,G?rbe, Tamás,Svedendahl Humble, Maria
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p. 338 - 346
(2017/12/26)
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- Easy and simple SiO2 immobilization of lipozyme CaLB-L: Its use as a catalyst in acylation reactions and comparison with other lipases
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In this study, lipase from Candida antarctica B (Lipozyme CaLB-L) was successfully immobilized on SiO2 through adsorption and used to obtain (R)-(+)-esters derived from (R,S)-1-phenylethanol. The new immobilized enzyme was compared with commercially immobilized lipases (Novozyme 435, Lipozyme 435 and Pseudomonas cepacia (PSC-II and PSD-I)). Lipozyme CaLB-L adsorbed onto SiO2 was found to be a good catalyst and, under optimal conditions, esters could be obtained with conversion 44percent, enantiomeric excess of product (eep) > 99percent, enantiomeric excess of substract (ees) 77percent and enantiomeric ratio (E) > 200. The lipase maintained enantioselectivity under adverse conditions, such as in organic solvents, with an excess of substrate and at different temperatures. The immobilized lipase could be reused five times with no significant loss of the activity.
- Mittersteiner, Mateus,Machado, Tayani M.,De Jesus, Paulo Cesar,Brondani, Patrícia B.,Scharf, Dilamara R.,Wendhausen, Renato
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p. 1185 - 1192
(2017/06/07)
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- New air-stable iron catalyst for efficient dynamic kinetic resolution of secondary benzylic and aliphatic alcohols
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We herein report a catalyst system for the dynamic kinetic resolution of secondary alcohols by combining the enzymatic resolution with an iron-catalyzed racemization. A new air-stable tricarbonyl (cyclopentadienone)iron complex is identified as the active racemization catalyst for this transformation without any additive. Various substrates including benzylic, heteroaromatic, aliphatic alcohols can be used and afford the corresponding esters in good yields and with excellent enantioselectivities.
- Yang, Qiong,Zhang, Na,Liu, Mingke,Zhou, Shaolin
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p. 2487 - 2489
(2017/06/01)
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- Efficient O-Acylation of Alcohols and Phenol Using Cp2TiCl as a Reaction Promoter
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A method has been developed for the conversion of primary, secondary, and tertiary alcohols, and phenol, into the corresponding esters at room temperature. The method uses a titanium(III) species generated from a substoichiometric amount of titanocene dichloride together with manganese(0) as a reductant, as well as methylene diiodide. It involves a transesterification from an ethyl ester, or a reaction with an acyl chloride. A radical mechanism is proposed for these transformations.
- Durán-Pe?a, María Jesús,Botubol-Ares, José Manuel,Hanson, James R.,Hernández-Galán, Rosario,Collado, Isidro G.
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supporting information
p. 3584 - 3591
(2016/07/28)
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- An extremely efficient and green method for the acylation of secondary alcohols, phenols and naphthols with a deep eutectic solvent as the catalyst
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The typical deep eutectic solvent [CholineCl][ZnCl2]3, easily prepared from choline chloride and zinc chloride, is green and useful for the acylation of secondary alcohols, phenols, and naphthols with acid anhydrides. Its efficiency allows the acylation of sterically hindered secondary alcohols and acid anhydrides to proceed in high yield under mild condition. The catalyst is cheap, easy to handle, conveniently synthesized in a single step, and recyclable for several times without significant loss of catalytic activity.
- Nguyen, Hai Truong,Tran, Phuong Hoang
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p. 98365 - 98368
(2016/10/31)
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- Highly Productive and Enantioselective Enzyme Catalysis under Continuous Supported Liquid–Liquid Conditions Using a Hybrid Monolithic Bioreactor
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Enzyme-containing ionic liquids (ILs) were immobilized in cellulose-2.5-acetate microbeads particles embedded in a porous monolithic polyurethane matrix. This bioreactor was used under continuous liquid-liquid conditions by dissolving the substrates in a nonpolar organic phase immiscible with the ILs, thereby creating a biphasic system. Lipases (candida antarctica lipase B, CALB, candida rugosa lipase, CRL) were used to catalyze the enantioselective transesterification of racemic (R,S)-1-phenylethanol with vinyl butyrate and vinyl acetate, the esterification of (+/-)-2-isopropyl-5-methylcyclohexanol with propionic anhydride and the amidation of (R,S)-1-phenylethylamine with ethyl methoxyacetate. With this unique setup, very high productivities, that is, turnover numbers (TONs) up to 5.1×106 and space-time yields (STYs) up to 28 g product L?1 h?1, exceeding the corresponding values for batch-type reactions by a factor of 3100 and 40, respectively, were achieved while maintaining or even enhancing enantioselectivity compared to batch reactions via kinetic resolution. To our best knowledge, this is the first continuously operated bioreactor using supported liquid-liquid conditions that shows these features in the synthesis of chiral esters and amides.
- Sandig, Bernhard,Buchmeiser, Michael R.
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p. 2917 - 2921
(2016/11/02)
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- Low-temperature enzymatic hydrolysis resolution in mini-emulsion media
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A low-temperature mini-emulsion medium for the enzymatic resolution of 1-phenylethanol is described for the first time. The enzymatic hydrolysis resolution of 1-phenylethyl esters with different chain-lengths in the presence of Candida antarctica lipase B in mini-emulsion media was shown to be significantly controlled by temperature. In this system, the direct effect of temperature on the mini-emulsion size was observed. For the longer 1-phenylethyl ester, 1-phenylethyl dodecanoate, the enzymatic resolution was promoted exclusively at low temperatures. The preparative mini-emulsion enzymatic reaction of 1-phenylethyl dodecanoate at 4°C afforded the isolation of (R)-phenylethanol with a yield of 36 % with an ee of 99 %. (S)-Phenylethanol was isolated with a 51 % yield with an ee of 79 %.
- Louren?o, Nuno M.T.,Matias, Sara C.,Altas, Margarida C.,Fonseca, Luis P.
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p. 810 - 816
(2015/03/31)
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- Combinatorial library based engineering of candida antarctica lipase a for enantioselective transacylation of sec-alcohols in organic solvent
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A method for determining lipase enantioselectivity in the transacylation of sec-alcohols in organic solvent was developed. The method was applied to a model library of Candida antarctica lipase A (CalA) variants for improved enantioselectivity (E values)
- Wikmark, Ylva,Svedendahl Humble, Maria,B?ckvall, Jan-E.
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supporting information
p. 4284 - 4288
(2015/04/14)
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- A general protein purification and immobilization method on controlled porosity glass: Biocatalytic applications
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A general combined purification and immobilization method to facilitate biocatalytic process development is presented. The support material, EziG, is based on controlled porosity glass (CPG) or polymer-coated versions thereof (HybCPG) and binds protein affinity tags. Biocatalytic reactions in aqueous and organic media with seven enzymes of biocatalytic interest are shown. This journal is the Partner Organisations 2014.
- Engelmark Cassimjee,Kadow,Wikmark,Svedendahl Humble,Rothstein,Rothstein,B?ckvall
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supporting information
p. 9134 - 9137
(2014/08/05)
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- Core-Shell Composite as the Racemization Catalyst in the Dynamic Kinetic Resolution of Secondary Alcohols
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Beta-Silicalite-1 core-shell microcomposites with controllable shell thickness were synthesized and used as racemization catalysts in the one-pot dynamic kinetic resolution (DKR) of secondary alcohols by using lipase-catalyzed transesterification. The inert Silicalite-1 shell covered the external acidic sites of the Beta zeolite core, suppressing dehydration and non-enantioselective transesterification of the alcohol. The alcohols could penetrate the Silicalite-1 shell to access the acidic sites at the core Beta for racemization, however, the enzymatically formed (R)-esters were excluded owing to their larger size. As a result, the high ee of the (R)-ester products was conserved and dehydration side products were minimized. Owing to the shape selective nature of the composite racemization catalyst, small and readily available acyl donors could be used in the enzyme-catalyzed transesterification to obtain the esters with high enantiopurity. The DKR of 1-phenylethanol with isopropenyl acetate using an optimized core-shell catalyst, CS-60, gave 92% selectivity to ester formation and the desired (R)-1-phenylethyl acetate was formed with 94% ee.
- Wang, Jie,Do, Dong-Minh,Chuah, Gaik-Khuan,Jaenicke, Stephan
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p. 247 - 254
(2013/03/13)
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- Molecular recognition driven catalysis using polymeric nanoreactors
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The concept of using polymeric micelles to catalyze organic reactions in water is presented and compared to surfactant based micelles in the context of molecular recognition. We report for the first time enzyme-like specific catalysis by tethering the catalyst in the well-defined hydrophobic core of a polymeric micelle.
- Cotanda, Pepa,O'Reilly, Rachel K.
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supporting information
p. 10280 - 10282,3
(2020/09/09)
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- Functionalized organocatalytic nanoreactors: Hydrophobic pockets for acylation reactions in water
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The effect of covalently attaching 4-(dimethylamino)pyridine (DMAP) functionality to the hydrophobic core of a polymeric micelle in water has been investigated in the context of acylation reactions employing non-water-soluble substrates. For this purpose a novel temperature-responsive polymeric micelle has been synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization techniques. The reactivity of the tethered organocatalyst within the nanostructure was found to be extremely high, improving in some cases the acylation rates up to 100 times compared to those for unsupported DMAP in organic solvents. Moreover, the catalytic nanoreactors have been demonstrated to be capable of reuse up to 6 times while maintaining high activity.
- Cotanda, Pepa,Lu, Annhelen,Patterson, Joseph P.,Petzetakis, Nikos,O'Reilly, Rachel K.
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scheme or table
p. 2377 - 2384
(2012/06/29)
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- Enabling industrial biocatalytic processes by application of silicone-coated enzyme preparations
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Composite particles of the commercial lipase preparation NZ435 and silicone (silcoat-NZ435) have recently been described as promising biocatalysts for synthetic use. In this study, their actual potential for enhanced performance in industrial applications was evaluated, focusing on scenarios where carrier disintegration and catalyst leaching constitute key limitations. All three investigated model reactions, the syntheses of myristyl myristate, poly(ethylene glycol) 400-coconut fatty acid monoester and ethylene oxide and propylene oxide copolymer (EO/PO)-oleic acid diester, were considerably improved in terms of the maximal number of reaction cycles performed with the same batch of catalyst, and consequently in terms of the obtainable product amount. The total turnover numbers (TTN) increased by a factor up to 50, making the realization of this type of reactions in an industrial process more feasible. The utility of silcoat-NZ435 for stereoselective transformations was demonstrated with the enantioselective acylation of 1-phenylethanol with vinyl butyrate, in which full retention of the excellent stereoselectivity of native NZ435 was observed. Moreover, it was demonstrated for the first time that the methodology by which silcoat-catalysts are obtained can be successfully transferred to alternative carriers and enzymes (e.g., protease, esterase and laccase), opening a broad field for the implementation and advancement of biocatalysis in industrial processes. Copyright
- Nieguth,Eckstein,Wiemann,Thum,Ansorge-Schumacher
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experimental part
p. 2522 - 2528
(2011/11/29)
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- Facile preparation of recyclable biocatalyst-decorated magnetic nanobeads in aqueous media
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A facile process was developed to manufacture biocatalyst-conjugated magnetic nanobeads, which afford no loss of the intrinsic activity and enantioselectivity of biocatalysts. Up to 90% of their activities remained after six-time recycling in aqueous media.
- Sim, Yong Kyun,Jung, Suhyun,Lim, Jung Yun,Kim, Juhyun,Kim, Seong-Ho,Song, Bong Keun,Kim, Bum Tae,Lee, Hyuk,Park, Seongsoon
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supporting information; experimental part
p. 1041 - 1043
(2011/03/20)
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- Dynamic kinetic resolution of secondary aromatic alcohols with new efficient acyl donors
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A new and efficient dynamic kinetic resolution (DKR) process of secondary aromatic alcohols by using long carbon-chain esters as acyl donors has been developed. During the process, the transesterification catalyzed by CD8604 was found to be the main reason for the decrease in enantiomeric excess (ee). Using complex acyl donors, such as 4-chlorophenyl valerate, we could effectively inhibit the resin-catalyzed transesterification, and an excellent ee value (>99%) at high yield (>99%) was achieved. The mechanism for the inhibition of resin-catalyzed transesterification is believed to be the formation of micro-micelles in the pores of CD8604. It is noteworthy that the system can be reused more than 20 times without a loss of yield or ee value.
- Xu, Gang,Chen, Yongjun,Wu, Jianping,Cheng, Yongmei,Yang, Lirong
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experimental part
p. 1373 - 1378
(2011/11/06)
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- Ruthenium pincer-catalyzed acylation of alcohols using esters with liberation of hydrogen under neutral conditions
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Acylation of secondary alcohols using non-activated esters, in particular symmetrical esters (such as ethyl acetate), is achieved under neutral conditions with the liberation of molecular hydrogen. This unprecedented, environmentally benign reaction is homogenously catalyzed by a dearomatized ruthenium pincer PNN complex. Copyright
- Gnanaprakasam, Boopathy,Ben-David, Yehoshoa,Milstein, David
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supporting information; experimental part
p. 3169 - 3173
(2011/02/23)
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- Dynamic kinetic resolution of secondary alcohols combining enzyme-catalyzed iransesterification and zeolite-catalyzed racemization
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Hydrophobic zeolite beta containing low concentrations of Zr or Al was found to be a good catalyst for the racemization of 1-phenylethanol. The formation of styrene as a side product could be minimized by reducing the metal concentration in the zeolite be
- Zhu, Yongzhong,Fow, Kam-Loon,Chuah, Gaik-Khuan,Jaenicke, Stephan
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p. 541 - 547
(2007/10/03)
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- (S)-Selective kinetic resolution and chemoenzymatic dynamic kinetic resolution of secondary alcohols
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(S)-Selective kinetic resolution was achieved through the use of a commercially available protease, which was activated with a combination of two different surfactants. The kinetic resolution (KR) process was optimized with respect to activation of the protease and to the acyl donor. The KR proved to be compatible with a range of functionalized sec-alcohols, giving good to high enantiomeric ratio values (up to >200). The enzymatic resolution was combined with a ruthenium-catalyzed racemization to give an (S)-selective dynamic kinetic resolution (DKR) of sec-alcohols. The DKR process works under very mild reaction conditions to give the corresponding esters in high yields and with excellent enantioselectivities.
- Boren, Linnea,Martin-Matute, Belen,Xu, Yongmei,Cordova, Armando,Baeckvall, Jan-E.
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p. 225 - 232
(2007/10/03)
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- Efficient dynamic kinetic resolution of secondary alcohols with a novel tetrafluorosuccinato ruthenium complex
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Dynamic kinetic resolution (DKR) of a series of secondary alcohols has been conducted with a novel dinuclear ruthenium complex, bearing tetrafluorosuccinate and (rac)-BINAP ligands as the racemization catalyst. Novozym 435 has been used as the enzyme, and isopropyl butyrate as the acyl donor. Five substrates underwent DKR successfully: an aliphatic and an aromatic secondary alcohol, an aromatic alcohol with an electron-withdrawing substituent on the phenyl ring, an aromatic alcohol bearing an electron-donating substituent on the ring and a heteroaromatic secondary alcohol. The catalyst performed optimally at 70 °C. Typically the reaction reached complete conversion within 1 day with 0.1 mol % of racemization catalyst relative to the substrate. The addition of the ketone corresponding to the substrate stabilizes the active Ru complex and, therefore, increases the rate of the reaction.
- van Nispen, Sjoerd F.G.M.,van Buijtenen, Jeroen,Vekemans, Jef A.J.M.,Meuldijk, Jan,Hulshof, Lumbertus A.
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p. 2299 - 2305
(2007/10/03)
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- Removal of the acyl donor residue allows the use of simple alkyl esters as acyl donors for the dynamic kinetic resolution of secondary alcohols
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The dynamic kinetic resolution of secondary alcohols using a lipase and a ruthenium catalyst as developed by Baeckvall required some improvements to make it suitable for its use in an industrial process. The use of p-chlorophenyl acetate as acyl donor is not desirable in view of the toxicity of the side product. We herein report that simple alkyl esters can be used as acyl donors if the alcohol or ketone residue formed during the enzymatic acylation is continuously removed during the reaction. The addition of a ketone speeds up the racemisation process and allowed us to reduce the amounts of enzyme and ruthenium catalyst. The scope of this method was explored and a suitable range of acyl donors found. Various benzylic and aliphatic alcohols were reacted using isopropyl butyrate or methyl phenylacetate as acyl donor and in most cases the ester was isolated in >95% yield and 99% ee. Furthermore, it was demonstrated that the alcohol by-products of the enzymatic resolution could be used as the hydrogen source in the asymmetric reductive transesterification of ketones.
- Verzijl, Gerard K.M.,De Vries, Johannes G.,Broxterman, Quirinus B.
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p. 1603 - 1610
(2007/10/03)
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- PROCESS FOR THE PREPARATION OF ENANTIOMERICALLY ENRICHED ESTERS AND ALCOHOLS
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The invention relates to a process for the preparation of an enantiomerically enriched ester, in which a mixture of the enantiomers of the corresponding chiral secondary alcohol in the presence of a racemisation catalyst for the substrate is subjected to an enantioselective acylation with the aid of an acyl donor and a stereoselective acylation catalyst upon which the enantiomerically enriched ester and an acyl donor residue are formed, in the presence of a carbonyl compound and wherein the racemisation catalyst comprises at least one ligand and a metal M chosen from group IIIa, IIIb, IVb of the periodic system, preferably Al.
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Page/Page column 19
(2010/02/10)
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- An S-selective lipase was created by rational redesign and the enantioselectivity increased with temperature
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(Chemical Equation Presented) Higher activity with larger pockets: The figure shows a superposition of intermediates that occur in acyl transfer to (S)-1-phenylethanol catalyzed by Candida antarctica lipase B (CALB). Wild-type CALB cannot accomodate the p
- Magnusson, Anders O.,Takwa, Mohamad,Hamberg, Anders,Hult, Karl
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p. 4582 - 4585
(2007/10/03)
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- METHOD OF PREPARATION OF OPTICALLY ACTIVE ALCOHOLS
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The present invention relates to a method for preparing chiral alcohol having optical activity. More specifically, the present invention relates to a method for preparing (S)-chiral alcohol with a high yield and a high optical purity by mixing achiral substrates such as racemic alcohol or ketone with metal catalyst and protein hydrolase to perform a dynamic kinetic resolution reaction.
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Page/Page column 20-21
(2010/02/10)
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- Mapping the substrate selectivity and enantioselectivity of esterases from thermophiles
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To identify potential applications of nineteen esterases from thermophiles, we mapped their substrate selectivity and enantioselectivity using a library of 50 esters. We measured the selectivities colorimetrically using Quick E, which uses pH indicators to detect hydrolysis and a chromogenic reference compound as an internal control. The substrate selectivity mapping revealed one esterase, E018b, with a strong preference for acetyl esters (14- to 25-fold over hexanoate). The enantioselectivity mapping revealed a number of cases of high enantioselectivity. Thirteen of the 19 esterases showed moderate or better enantioselectivity (>19) toward 1-phenethyl butyrate favoring the (R)-enantiomer and two esterases (E008, E013) showed moderate or better enantioselectivity (>20) toward methyl 2-chloropropionate favoring the (S)-enantiomer. Three esterases (E001, E004, E005) showed high (>46) enantioselectivity toward menthyl acetate favoring the (R)-enantiomer. This rapid mapping of the selectivity simplifies the characterization of new enzymes.
- Somers, Neil A.,Kazlauskas, Romas J.
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p. 2991 - 3004
(2007/10/03)
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- (S)-selective dynamic kinetic resolution of secondary alcohols by the combination of subtilisin and an aminocyclopentadienylruthenium complex as the catalysts
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A new procedure for the dynamic kinetic resolution (DKR) of racemic alcohols into single enantiomers is described. This procedure employs surfactant-treated subtilisin as an (S)-selective resolving catalyst and an aminocyclopentadienylruthenium complex as a racemizing catalyst. The DKR is performed best in the presence of an acyl donor such as trifluoroethyl butyrate in THF at room temperature. Eight simple secondary alcohols have been efficiently resolved with high optical purities and good yields. The subtilisin-based DKR is complementary in stereoselectivity to its lipase-based counterpart. For an acyl-carrying alcohol, both subtilisin- and lipase-based DKRs have proceeded equally well to give a pair of enantiomeric products (>99.5% ee each) with opposite optical rotations in high yields (94-95%). Copyright
- Kim, Mahn-Joo,Chung, Yong Il,Choi, Yoon Kyung,Lee, Han Ki,Kim, Daeho,Park, Jaiwook
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p. 11494 - 11495
(2007/10/03)
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- Highly enantioselective aminoacylase-catalyzed transesterification of secondary alcohols
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The aminoacylase (N-acyl-L-amino acid amidohydrolase; E.C. 3.5.1.14) from Aspergillus melleus, a readily available inexpensive enzyme, catalyzes the transesterification of a wide range of chiral secondary arylalkanols with essentially absolute stereoselectivity (E> 500). Moreover, the productivities obtained with 1-phenylethanol, 1-phenylpropanol, 1-(1-naphthyl)ethanol and 1- (2-naphthyl)ethanol were substantially higher than those in the corresponding lipase-catalyzed transesterifications. (C) 2000 Elsevier Science Ltd.
- Bakker,Spruijt,Van Rantwijk,Sheldon
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p. 1801 - 1808
(2007/10/03)
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- Improved enzyme activity and enantioselectivity in organic solvents by methyl-β-cyclodextrin
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The use of enzymes in organic solvents to introduce chirality to a number of relevant organic compounds has been well documented. However, there are still major drawbacks in such applications, in particular the frequently much lower enzyme activity under nonaqueous conditions. In addition, the reaction outcome (substrate enantioselectivity and reaction rates) cannot be accurately predicted. To overcome these limitations, herein we introduce methyl-β-cyclodextrin (MβCD) as a new macrocyclic additive to simultaneously enhance the activity and enantioselectivity of dehydrated subtilisin Carlsberg suspended in neat organic solvents. MβCD was efficient in dramatically increasing the activity and significantly improving the enantioselectivity of subtilisin in co-lyophilizates when compared to the powder lyophilized from buffer alone. The initial rate determined for the transesterification between sec-phenethyl alcohol and vinyl butyrate increased by up to 164-fold and the enantioselectivity could be doubled. In addition, marked solvent effects were noted. To investigate the possible relationship between enzyme structure and these kinetic data, the secondary structure of subtilisin was investigated by Fourier transform infrared (FTIR) spectroscopy under all relevant conditions. Using the α-helix content determined from the amide I vibrational band as the main quantitative parameter, we found that MβCD is partially efficient in ameliorating dehydration-induced structural perturbations. Suspension of the subtilisin - MβCD co-lyophilizate in the various solvents revealed solvent-induced structural perturbations in some of them (e.g., acetonitrile), while no such changes were observed in others (e.g., THF and 1,4-dioxane). For the first time the results demonstrated that enantioselectivity and structural intactness in the various solvents were clearly related. Increase in the enzyme activity in contrast is mainly caused by increased structural mobility of subtilisin in the solvents by MβCD. We conclude that it is important to carefully select the additive and the solvent system to achieve high enantioselectivity and activity in such applications. Simultaneous improvement of both enzyme properties requires careful optimization of the enzyme formulation and proper selection of a suitable solvent. FTIR spectroscopy has proven to be a very valuable methodology to structurally guide such an optimization procedure.
- Griebenow, Kai,Laureano, Yanira Diaz,Santos, Angelica M.,Clemente, Ileana Montanez,Rodriguez, Luiz,Vidal, Michael W.,Barletta, Gabriel
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p. 8157 - 8163
(2007/10/03)
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- Application of structure-based thermodynamic calculations to the rationalization of the enantioselectivity of subtilisin in organic solvents
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The effect of organic solvents on the selectivity of lyophilized or CLEC (cross-linked enzyme crystals)-subtilisin in the resolution of sec-phenethyl alcohol and trans-sobrerol was studied. A theoretical model, that tries to predict solvent effects on ena
- Colombo, Giorgio,Ottolina, Gianluca,Carrea, Giacomo,Bernardi, Anna,Scolastico, Carlo
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p. 1205 - 1214
(2007/10/03)
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- Biocatalysis in Organic Synthesis. 9. Highly Enantioselective Kinetic Resolution of Secondary Alcohols Catalyzed by Acylase
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A new catalytic activity of the enzyme acylase I (AA-I) from Aspergillus species has been found. Although this enzyme had previously been used only in the hydrolysis of N-acylamino acids, we have found that it is a highly efficient catalyst for transesterifications using vinyl esters as acyl donors. The method has been applied to the kinetic resolution of a variety of secondary alcohols.
- Faraldos, Juan,Arroyo, Elisa,Herradón, Bernardo
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p. 367 - 370
(2007/10/03)
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- Cross-linked crystals of subtilisin: Versatile catalyst for organic synthesis
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Cross-linked enzyme crystals (CLECs) of subtilisin exhibit excellent activity in aqueous and various organic solvents. This catalyst is more stable than the native enzyme in both aqueous and mixed aqueous/organic solutions. Subtilisin-CLEC was shown to be a versatile catalyst. It was used for the syntheses of peptides and peptidomimetics, mild hydrolysis of amino acid and peptide amides, enantio- and regioselective reactions, and transesterifications.
- Wang, Yi-Fong,Yakovlevsky, Kirill,Zhang, Bailing,Margolin, Alexey L.
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p. 3488 - 3495
(2007/10/03)
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- Oxidative Transformations of Aldazines and Ketazines with Organic Peroxyacids
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Oxidation of aromatic aldazines and ketazines with various peroxycarboxylic acids was investigated.It was found that one part of azine molecule 2 was converted into carbonyl compound 1 or related acid 3 while the second part was transformed into carboxylic ester 4 related to peroxyacid used as an oxidant.It was revealed that aromatic azines could be used as a source of diazaarylmethanes and mechanisms of reactions studied were postulated. aldazines, carboxylic esters, ketazines, oxidation, peroxycarboxylic acids
- Mlochowski, J.,Giurg, M.
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p. 2333 - 2342
(2007/10/02)
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- Anhydrides as Acylating Agents in Lipase-Catalyzed Stereoselective Esterification of Racemic Alcohols
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A new enzymatic method for the resolution of optically active alcohols from racemates is reported.It involves lipase-catalyzed esterification in organic solvents, with acetic, propionic, or butyric anhydrides as acylating agents.Lipase Amano P, from Pseudomonas fluorescens, adsorbed on Celite 577, was employed as stereoselective catalyst.Under these reaction conditions, the enzyme is not chemically modified by the anhydrides.A number of primary and secondary alcohols have been obtained in high optical purity by this procedure.
- Bianchi, Daniele,Cesti, Pietro,Battistel, Ezio
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p. 5531 - 5534
(2007/10/02)
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- Resolution of Racemic Mixtures via Lipase Catalysis in Organic Solvents
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Yeast lipase and porcine pancreatic lipase have been found to vigorously function in nearly anhydrous organic solvents and catalyze the reactions of esterification and transesterification, respectively, in highly stereoselective manner.With use of these enzymatic processes, a number of optically active alcohols, carboxylic acids, and their esters have been prepared on a gram scale.
- Kirchner, Gerald,Scollar, Mark P.,Klibanov, Alexander M.
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p. 7072 - 7076
(2007/10/02)
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- Preparative Production of Optically Active Esters and Alcohols Using Esterase-Catalyzed Stereospecific Transesterification in Organic Media
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A novel enzymatic approach to the production of optically active alcohols and esters from racemates is developed.It involves the use of esterase catalyzed transesterifications carried out in biphasic aqueous-organic mixtures.Water-insoluble substrates constitute the organic phase, while the enzyme is located in the aqueous phase.Since the fraction of the latter phase can be made very low, such an arrangement solves the problem of both the competition of an alcohol (the nucleophile) with water in the enzymatic reaction and poor solubility of most organic esters and alcohols in water.By use of porous supports (Sepharose or Chromosorb) filled with aqueous solutions of hog liver carboxyl esterase as a stereoselective catalyst and methyl propionate as a matrix ester, the following optically active alcohols and their propionic esters were produced on a preparative scale: 3-methoxy-1-butanol, 3-methyl-1-pentanol, 3,7-dimethyl-1-octanol, and β-citronellol.To overcome a rather narrow substrate specificity of hog liver carboxyl esterase, a nonspecific lipase from yeast (Candida cylindracea) also was employed as a stereoselective transesterification catalyst.Using an aqueous solution of this enzyme confined to the pores of Chromosorb and tributyrin as a matrix ester, we have prepared gram amounts of the following optically active alcohols and their butyric esters: 2-butanol, sec-phenethyl alcohol, 2-octanol, 1-chloro-2-propanol and 2,3-dichloro-1-propanol (subsequently nonenzymatically converted to optically active propylene oxide and epichlorohydrin, respectively), 6-methyl-5-hepten-2-ol, and 1,2-butanediol.
- Cambou, Bernard,Klibanov, Alexander M.
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p. 2687 - 2692
(2007/10/02)
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