- Causes of unreproducibility of C. rugosa Lipase-catalyzed reactions in slightly hydrated organic media
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Lipase activity, measured as hydrolysis of tributyrin is a valid assay to quantify the lipase activity of a lyophilized crude lipase in hydrolysis reactions but it is not useful to predict the catalytic activity in lipase- catalyzed reactions in organic media. Three factors control the catalytic activity in these media: i) relative proportion of isoenzymes; ii) amount of water in the lyophilized crude enzyme and iii) amount of lipase protein in the commercial powder. Thus we propose two simple reaction tests: i) heptyl oleate synthesis (specific of lipases), ii) enantioselective esterification of (R) or (S) 2-(3-benzoyl)phenyl propionic acid. This methodology is applied to different crude lipases of Candida rugosa, obtained in different fermenter conditions and shows the origin of the unreproducibility of the synthetic data.
- Dominguez De Maria, Pablo,Sinisterra Gago, Jose V.
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- Enhancing the enantioselectivity of lipase in transesterification by substrate matching: an enzyme memory based approach.
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The substrate matching strategy is described as a new approach for effectively enhancing the lipase enantioselectivity in organic solvent. In the lipase-catalyzed transesterifications of 3a-c, higher enantioselectivities have been achieved using 1a-c, res
- Lee,Choi,Kim
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- A method for the synthesis of pyridine-based C2-symmetrical chiral nucleophilic organocatalysts via Pd-catalyzed coupling
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A one step Pd-catalyzed coupling methodology involving a reaction between a chiral diamine and a 2-bromo-4-(alkylamino)pyridine, was developed for the synthesis of novel C2-symmmetrical chiral compounds with chemical yields of up to 87%. The or
- Yazicio?lu, Emre Y.,Tanyeli, Cihangir
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- Multicomponent thermosensitive systems for biocatalysts
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Composite matrices based on macroporous silica modified by N-vinylcaprolactam copolymers with diallyldimethylammonium chloride and with 2-hydroxyethyl methacrylate were obtained. Lipase from Pseudomonas fluorescens was immobilized on the obtained material
- Kapustin,Vikhrov,Gorokhova,Generalova,Kalyazina,Murzabekova,Zubov
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- A Practical NMR-Based High-Throughput Assay for Screening Enantioselective Catalysts and Biocatalysts
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Two NMR-based approaches for highthroughput screening of enantioselective catalysts and biocatalysts are described. One version makes use of pseudo-enantiomers or pseudo-meso-compounds based on 13C-labeling. A throughput of at least 1400 ee determinations per day is possible by using an appropriate flow-through cell and an autosampler. The other approach is based on traditional diastereomer formation using a chiral reagent or complexing agent. The ee values are accurate to within ±2% and ±5% of the true values.
- Reetz, Manfred T.,Eipper, Andreas,Tielmann, Patrick,Mynott, Richard
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- A mechanistic investigation of the kinetic resolution of secondary aromatic alcohols using a ferrocene-based planar chiral 4-(dimethylamino)pyridine catalyst
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A detailed computational and kinetic analysis of the acetylation of 1-phenylethanol with acetic anhydride catalyzed by planar chiral 4-(dimethylamino)pyridine (DMAP) catalyst (-)-1 is presented. The study includes a computational investigation of the pote
- Mesas-Sánchez, Laura,Dinér, Peter
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- Enzymatic resolution of alcohols coupled with ruthenium-catalyzed racemization of the substrate alcohol
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A specifically designed acyl donor, an efficient enzyme, and a stable and reliable ruthenium catalyst are fundamental for the resolution of the racemic alcohols described here (see scheme on the right). For R1 = Ph and R2 = Me, 100% conversion into the corresponding acetate was achieved with greater than 99.5% cc.
- Larsson,Persson,Backvall
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- Immobilization of burkholderia cepacia on pristine or functionalized multi?walled carbon nanotubes and application on enzymatic resolution of (RS)?1?phenylethanol
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The immobilization of Burkholderia cepacia lipase (BCL) on pristine or functionalized multi-walled carbon nanotubes (MWCNTs) was studied in the resolution of (RS)-1-phenylethanol. For the functionalization, three treatments were used, these being in Hsub
- Dias, Michele R. G.,De Pauloveloso, Alysson,Do Amaral, Lilian F. M.,Betim, Rhaísa T.,Nascimento, Maria G.,Piliss?o, Cristiane
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- Kinetics and Mechanism of Nucleophilic Displacements with Heterocycles as Leaving Groups. Part 12. Regio- and Stereo-chemistry of Nucleophilic Displacement and Solvolysis Reactions of N(α-Methylallyl)- and N-(α-Phenylethyl)-pyridiniums
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N-(α-Methylallyl)pyridiniums rearrange to the N-(γ-methylallyl) analogues in a process analogous to ion return.In the tricyclic series the process (9) -> (4) occurs spontaneously.In the monocyclic series (1) can be isolated and thermally rearranged into (2); this rearrangement is intramolecular.N-(α-Phenylethyl)pyridinium solvolyse in HOAc-NEt3 with predominant inversion of configuration (90percent).In the 2,4,6-triphenyl series this occurs spontaneously.The isolated 1-(α-phenylethyl)-2-isopropyl-4,6-diphenylpyridinium solvolyses in chlorobenzene with first-order kinetics and with racemisation.
- Katritzky, Alan R.,Ou, Yu Xiang,Musumarra, Giuseppe
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- Palladium catalysts supported on N-functionalized hollow vapor-grown carbon nanofibers: The effect of the basic support and catalyst reduction temperature
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The basic N-functionalized vapor-grown carbon nanofibers (N-VGCF) were synthesized by post-treating oxidized VGCFs in gaseous NH3 at high temperature (ammonolysis) prior to Pd addition by sol immobilization. The catalysts were characterized by nitrogen adsorption, hydrogen temperature programmed desorption, adsorption microcalorimetry and by SEM and TEM. Catalytic activity was evaluated in a model reaction, synthesis of (R)-1-phenylethyl acetate starting from hydrogenation of acetophenone to racemic 1-phenylethanol over Pd supported on N-VGCFs, at 70 °C under atmospheric hydrogen pressure in toluene, followed by acylation over an immobilized lipase in the same reaction pot. The main parameters investigated in this work were the role of the basic N-VGCF supports as well as the reduction procedure of the supported Pd catalysts (Pd-N-VGCF). The results revealed that the catalytic activity of the Pd-N-VGCF catalysts was highly dependent on the reduction procedure. The highest desired product yield, 35%, was obtained over a Pd-N-VGCF catalyst when the support was treated at 400 °C with gaseous ammonia prior to Pd addition.
- Sahin, Serap,M?ki-Arvela, P?ivi,Tessonnier, Jean-Philippe,Villa, Alberto,Reiche, Sylvia,Wrabetz, Sabine,Su, Dangsheng,Schl?gl, Robert,Salmi, Tapio,Murzin, Dmitry Yu.
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- A practical high-throughput screening system for enantioselectivity by using FTIR spectroscopy
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For the first time FTIR spectroscopy has been applied to the measurement of enantiomeric purity. The underlying concept is based on the use of pseudo-enantiomers that are 13C-labeled at appropriate positions. Upon applying Lambert-Beer's law in
- Tielmann, Patrick,Boese, Matthias,Luft, Martin,Reetz, Manfred T.
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- 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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- PQXdpap: Helical Poly(quinoxaline-2,3-diyl)s Bearing 4-(Dipropylamino)pyridin-3-yl Pendants as Chirality-Switchable Nucleophilic Catalysts for the Kinetic Resolution of Secondary Alcohols
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Helically chiral poly(quinoxaline-2,3-diyl)s bearing 4-(dipropylamino)pyridin-3-yl pendants at the 5-position of the quinoxaline ring (PQXdpap) exhibited high catalytic activities and moderate to high selectivities (up to s = 87) in the acylative kinetic resolution of secondary alcohols. The solvent-dependent helical chirality switching of PQXdpap between pure toluene and a 1:1 mixture of toluene and 1,1,2-trichloroethane enabled the preparation of either compound of a pair of enantiomerically pure alcohols (>99% ee) from a single catalyst.
- Murakami, Ryo,Suginome, Michinori,Yamamoto, Takeshi
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supporting information
p. 8711 - 8716
(2021/11/24)
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- Lipase from pseudomonas cepacia immobilized into ZIF-8 as bio-catalyst for enantioselective hydrolysis and transesterification
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Enzyme immobilization in MOFs offers retained enzyme integrity and activity, enhanced stability, and reduced leaching. In this work, Pseudomonas cepacia lipase (PCL) was successfully immobilized into the Zeolitic imidazolate framework-8 (ZIF-8) by physical adsorption. The amounts of PCL in the immobilized enzyme (PCL?ZIF-8) was determined to be 16.7 % (200.5 mg PCL/g ZIF-8). Furthermore, the immobilized enzyme was applied as efficient bio-catalyst for enantioselective hydrolysis of 2-phenylpropionic acid (2-PPA) ester enantiomers and enantioselective transesterification of 1-phenylethanol enantiomers. The enzymatic activity of the immobilized enzyme was three times more than that of free PCL in enantioselective hydrolysis system, and the enantiomeric excess was maintained above 99 %. There was no significant difference in enzyme activity between immobilized PCL and free PCL in transesterification system. In addition, the immobilized enzyme showed good reusability in both hydrolysis (30.57 % of initial activity, 4 cycle) and transesterification reaction systems (64.38 % of initial activity, 6 cycle).
- Liu, Yu,Ou, Jian,Tang, Kewen,Xu, Weifeng,Yuan, Xin,Zhang, Panliang
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p. 132 - 140
(2021/01/06)
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- Pickering-Droplet-Derived MOF Microreactors for Continuous-Flow Biocatalysis with Size Selectivity
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Enzymatic microarchitectures with spatially controlled reactivity, engineered molecular sieving ability, favorable interior environment, and industrial productivity show great potential in synthetic protocellular systems and practical biotechnology, but their construction remains a significant challenge. Here, we proposed a Pickering emulsion interface-directed synthesis method to fabricate such a microreactor, in which a robust and defect-free MOF layer was grown around silica emulsifier stabilized droplet surfaces. The compartmentalized interior droplets can provide a biomimetic microenvironment to host free enzymes, while the outer MOF layer secludes active species from the surroundings and endows the microreactor with size-selective permeability. Impressively, the thus-designed enzymatic microreactor exhibited excellent size selectivity and long-term stability, as demonstrated by a 1000 h continuous-flow reaction, while affording completely equal enantioselectivities to the free enzyme counterpart. Moreover, the catalytic efficiency of such enzymatic microreactors was conveniently regulated through engineering of the type or thickness of the outer MOF layer or interior environments for the enzymes, highlighting their superior customized specialties. This study provides new opportunities in designing MOF-based artificial cellular microreactors for practical applications.
- Liang, Linfeng,Shi, Hu,Tian, Danping,Wang, Jun-Hao,Xue, Nan,Yang, Hengquan,Zhang, Xiaoming
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supporting information
p. 16641 - 16652
(2021/10/20)
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- PHANE-TetraPHOS, the First D2 Symmetric Chiral Tetraphosphane. Synthesis, Metal Complexation, and Application in Homogeneous Stereoselective Hydrogenation
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PHANE-TetraPHOS, a new D2 symmetric tetraphosphane based on the [2.2]paracyclophane scaffold, has been synthesized and characterized. The peculiarity of this system is the presence of four homotopic diphenylphosphane groups, exchangeable through C2 symmetry operations and consequently indistinguishable. Their spatial arrangement allows the simultaneous complexation of two metal atoms. Enantiomeric purity was attained at tetra-phosphane oxide level by fractional crystallization of the diastereomeric adducts obtained from the racemate with enantiopure dibenzoyltartaric acids. Alkaline treatment of diastereomerically pure adducts followed by exhaustive P?O groups reduction with HSiCl3 gave both PHANE-TetraPHOS antipodes in an enantiopure state. They were tested as rhodium ligands in the homogeneous enantioselective hydrogenation of some benchmark unsaturated compounds. Catalytic activity and enantiodiscrimination ability were found comparable to those exhibited by the complexes of the parent bidentate ligand PHANEPHOS, but only half a mole of precious chiral ligand was employed.
- Benincori, Tiziana,Cirilli, Roberto,Pierini, Marco,Rizzo, Simona,Terraneo, Giancarlo,Vaghi, Luca
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p. 2367 - 2374
(2021/06/25)
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- Acylative Dynamic Kinetic Resolution of Secondary Alcohols: Tandem Catalysis by HyperBTM and B?ckvall's Ruthenium Complex
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Non-enzymatic dynamic kinetic resolution (DKR) of secondary alcohols by enantioselective acylation using an isothiourea-derived HyperBTM catalyst and racemization of slowly reacting alcohol by B?ckvall's ruthenium complex is reported. The DKR approach fea
- Kinens, Artis,Balkaitis, Simonas,Ahmad, Omar K.,Piotrowski, David W.,Suna, Edgars
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p. 7189 - 7202
(2021/05/29)
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- Evaluation of gem-Diacetates as Alternative Reagents for Enzymatic Regio-and Stereoselective Acylation of Alcohols
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Geminal diacetates have been used as sustainable acyl donors for enzymatic acylation of chiral and nonchiral alcohols. Especially, it was revealed that geminal diacetates showed higher reactivity than vinyl acetate for hydrolases that are sensitive to acetaldehyde. Under optimized conditions for enzymatic acylation, several synthetically relevant saturated and unsaturated acetates of various primary alcohols were obtained in very high yields up to 98% without E/Z isomerization of the double bond. Subsequently, the acyl donor was recreated from the resulting aldehyde and reused constantly in acylation. Therefore, the developed process is characterized by high atomic efficiency. Moreover, it was shown that acylation using geminal diacetates resulted in remarkable regioselectivity by discriminating among the primary and secondary hydroxyl groups in 1-phenyl-1,3-propanediol providing exclusively 3-acetoxy-1-phenyl-propan-1-ol in good yield. Further, enzymatic kinetic resolution (EKR) and chemoenzymatic dynamic kinetic resolution (DKR) protocols were developed using geminal diacetate as an acylating agent, resulting in chiral acetates in high yields up to 94% with enantiomeric excesses exceeding 99%.
- Koszelewski, Dominik,Brodzka, Anna,Madej, Arleta,Trzepizur, Damian,Ostaszewski, Ryszard
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p. 6331 - 6342
(2021/05/06)
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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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- Enantioselective resolution of (±)-1-phenylethyl acetate using the immobilized extracellular proteases from deep-sea Bacillus sp. DL-1
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Bacillus sp. DL-1 was isolated from the deep sea of the Western Pacific Ocean and behaved very good resistance to NaCl. The extracellular proteases of Bacillus sp. DL-1 were found to exhibit excellent enantioselectivity for the kinetic resolution of (±)-1-phenylethyl acetate. To improve the stability of the enzyme, the immobilized extracellular proteases were preparated by using 60 g kieselguhr and 1-L crude fermentation broth containing extracellular proteases of Bacillus sp. DL-1, shaking at 25 °C, 200 r/min for 10 h. Every gram of kieselguhr adsorbed 25.7 mg extracellular protease and the enzymatic activity recovery was 79.86%. The immobilized proteases preserved about 35.8% of its activity after 6 repeated uses, which were also used as biocatalyst to asymmetrically hydrolyse (±)-1-phenylethyl acetate for the preparation of (R)-1-phenylethanol and (S)-1-phenylethyl acetate with high optical purities. The effects of pH, temperature, enzyme concentration, substrate concentration, reaction time and additives (metal ions/surfactants) on the resolution were investigated by single factor experiments. Under the optimal reaction conditions (10 mM (±)-1-phenylethyl acetate, 40 mg/mL immobilized extracellular proteases, pH 7.5 (Tris-HCl), 5% (v/v) methanol and 45 °C for 2 h), (R)-1-phenylethanol was generated with the e.e.p being > 97%, and the yield being 53%, respectively. Analogously, under the optimal reaction conditions (10-mM (±)-1-phenylethyl acetate, 360 mg/mL immobilized extracellular proteases, pH 6.0 (PB), 5% (v/v) DMSO and 35 °C for 1.5 h), (S)-1-phenylethyl acetate was generated with the e.e.s being over 99% and the yield being 79%, respectively. Compared with the extracellular proteases from Bacillus sp. DL-2, the immobilized extracellular proteases from Bacillus sp. DL-1 exhibited higher hydrolytic activity and could asymmetrically hydrolyse (±)-1-phenylethyl acetate by using higher substrate concentrations, shorter reaction times to obtain higher yields. Notably, the extracellular proteases of Bacillus sp. DL-1 were demonstrated to behave the same enantio-preference as those of most other reported esterases/lipases. Proteases from deep-sea Bacillus sp. DL-1 are promising biocatalysts for the synthesis of valuable chiral chemicals.
- Dong, Lu,Qi, Shujuan,Jia, Jianwei,Zhang, Yun,Hu, Yunfeng
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- Lipase-oxovanadium heterogeneous catalysis system: a robust protocol for the dynamic kinetic resolution of sec-alcohols
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Herein, we present a robust and eco-friendly dynamic kinetic resolution (DKR) protocol for secondary alcohols using a combined heterogeneous catalytic CAL?B/VOSO4 system at 50 °C in the relatively green solvent heptane. This catalytic system is
- De Almeida, Laiza A.,Marcondes, Thayna H.,Milagre, Cintia D. F.,Milagre, Humberto M. S.
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p. 2849 - 2858
(2020/04/09)
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- METHODS OF MAKING HIGH ENANTIOSELECTIVE SECONDARY ALCOHOLS
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A new process to synthesis of compound OBI-3424 R-form and S-form products is provided. The "R-form" compound OBI-3423 was first synthesized with 48% overall yield from compound OBI-3424-5 by installation of the labile phosphate motif at later stage. The stereo chemistry is established by 5 steps chemo-enzyme combination synthesis to afford 99% optical purity, After then, the "S-form" compound OBI-3424 is prepared with improving overall yield of 54% from compound OBI-3424-5. The stereo chemistry is established by 4 steps combination of chemo-enzyme synthesis with excellent optical purity of 99%.
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Paragraph 0111; 0115
(2020/09/08)
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- Thermal and Mechanical Stability of Immobilized Candida antarctica Lipase B: an Approximation to Mechanochemical Energetics in Enzyme Catalysis.
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Very recently, several successful enzymatic processes performed with mechanical activation have been disclosed; that is, despite the mechanical stress caused by High-Speed Ball-Milling, immobilized enzymes can retain activity. In the present study, the effect of thermal and mechanical stress was examined as potential inducers of enzymatic denaturation, when using either free, immobilized, or ground immobilized enzyme. The recorded observations show a remarkable stability of ground immobilized enzyme. Moreover, ground biocatalyst turns out to exhibit an increase of one order of magnitude in the efficiency of the catalytic process, maintaining excellent enantiodiscrimination, without significant activity loss even after four milling cycles. These observations rule out enzyme inactivation as direct consequence of the milling process. Additionally, boosted enzyme efficiency was used to optimize a relatively inefficient chiral amine resolution reaction, achieving a 25 % faster biotransformation (in 45 min) and yielding essentially enantiopure products (ee>99%, E>500).
- Pérez-Venegas, Mario,Tellez-Cruz, Miriam M.,Solorza-Feria, Omar,López-Munguía, Agustín,Castillo, Edmundo,Juaristi, Eusebio
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p. 803 - 811
(2019/12/11)
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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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- CALB immobilized onto magnetic nanoparticles for efficient kinetic resolution of racemic secondary alcohols: Long-term stability and reusability
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In this study, an immobilization strategy for magnetic cross-linking enzyme aggregates of lipase B from Candida antarctica (CALB) was developed and investigated. Magnetic particles were prepared by conventional co-precipitation. The magnetic nanoparticles were modified with 3-aminopropyltriethoxysilane (APTES) to obtain surface amino-functionalized magnetic nanoparticles (APTES–Fe3O4) as immobilization materials. Glutaraldehyde was used as a crosslinker to covalently bind CALB to APTES–Fe3O4. The optimal conditions of immobilization of lipase and resolution of racemic 1-phenylethanol were investigated. Under optimal conditions, esters could be obtained with conversion of 50%, enantiomeric excess of product (eep) > 99%, enantiomeric excess of substrate (ees) > 99%, and enantiomeric ratio (E) > 1000. The magnetic CALB CLEAs were successfully used for enzymatic kinetic resolution of fifteen secondary alcohols. Compared with Novozym 435, the magnetic CALB CLEAs exhibited a better enantioselectivity for most substrates. The conversion was still greater than 49% after the magnetic CALB CLEAs had been reused 10 times in a 48 h reaction cycle; both ees and eep were close to 99%. Furthermore, there was little decrease in catalytic activity and enantioselectivity after being stored at ?20 ?C for 90 days.
- Xing, Xiu,Jia, Jun-Qi,Zhang, Jing-Fan,Zhou, Zi-Wen,Li, Jun,Wang, Na,Yu, Xiao-Qi
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- Pickering Emulsion-Derived Liquid-Solid Hybrid Catalyst for Bridging Homogeneous and Heterogeneous Catalysis
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We describe a novel method to prepare a liquid-solid hybrid catalyst via interfacial growth of a porous silica crust around Pickering emulsion droplets, which allowed us to overcome the current limitations of both homogeneous and heterogeneous catalysts. The inner micron-scaled liquid (for example, ionic liquids) pool of the resultant catalyst can host free homogeneous molecular catalysts or enzymes to create a true homogeneous catalysis environment. The porous silica crust of the hybrid catalyst has excellent stability, which makes it amenable to packing directly in fixed-bed reactors for continuous flow catalysis. As a proof of concept, the enzymatic kinetic resolution of racemic alcohols, CrIII(salen) complex-catalyzed asymmetric ring opening of epoxides and Pd-catalyzed Tsuji-Trost allylic substitution reactions were used to verify the generality and versatility of our strategy for bridging homogeneous and heterogeneous catalysis. The hybrid catalyst-based continuous flow system exhibited a 1.6a16-fold enhancement in activity relative to homogeneous counterparts even over 1500 h, and the afforded enantioselectivities were completely equal to those obtained in the homogeneous counterpart systems. Interestingly, the catalytic efficiency can be tuned through rational engineering of the porous crust and the dimensions of the liquid pool, resulting in features of an innovatively designed catalyst. This contribution provides a new method to design efficient catalysts that can bridge the conceptual and technical gaps between homogeneous and heterogeneous catalysis.
- Zhang, Xiaoming,Hou, Yiting,Ettelaie, Rammile,Guan, Ruqun,Zhang, Ming,Zhang, Yabin,Yang, Hengquan
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supporting information
p. 5220 - 5230
(2019/03/11)
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- LipG9-mediated enzymatic kinetic resolution of racemates: Expanding the substrate-scope for a metagenomic lipase
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Enzymes are the main biocatalysts of biological systems and nowadays they play an important role in asymmetric organic synthesis. Microorganisms are the main source for enzymes, however, just a very small portion of them are culturable at lab conditions and, as an alternative, metagenomics approaches allow new enzymes to be accessed from so-called “non-culturable” microorganisms. Several classes of metagenomic enzymes have been described in literature. Nevertheless, studies about their potential for asymmetric biotransformation are underexploited. Therefore, we present our recent efforts to establish the substrate-scope of LipG9, a metagenomic lipase, in enzymatic kinetic resolution (EKR) of chiral substances. LipG9 was previously isolated, immobilized and successfully applied in EKR of aliphatic alcohols. In this study, a series of resolvable chiral substances were assayed with LipG9, and secondary benzyl alcohols/esters were preferentially resolved in a much superior enantioselectivity (E > 200) than those described for aliphatic alcohols (E from 4 to 63). In an opposite way, Im-LipG9 did not present activity for tertiary alcohols, amines and lactones. When compared to commercial lipases, Im-LipG9 enantioselectivity was superior to Candida rugosa lipase and equivalent to Candida antarctica lipase B. Thus, the chemo and enantioselectivity of LipG9 in EKR reactions were identified and its potential for asymmetric synthetic approaches was demonstrated.
- Thomas, Juliana Christina,Alnoch, Robson Carlos,Costa, Allen Carolina dos Santos,Bandeira, Pamela Taisline,Burich, Martha Daniela,Campos, Suelem Kluconski,de Oliveira, Alfredo Ricardo Marques,de Souza, Emanuel Maltempi,Pedrosa, Fabio de Oliveira,Krieger, Nadia,Piovan, Leandro
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- Enzyme-Decorated Covalent Organic Frameworks as Nanoporous Platforms for Heterogeneous Biocatalysis
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Sustainability in chemistry heavily relies on heterogeneous catalysis. Enzymes, the main catalyst for biochemical reactions in nature, are an elegant choice to catalyze reactions due to their high activity and selectivity, although they usually suffer from lack of robustness. To overcome this drawback, enzyme-decorated nanoporous heterogeneous catalysts were developed. Three different approaches for Candida antarctica lipase B (CAL-B) immobilization on a covalent organic framework (PPF-2) were employed: physical adsorption on the surface, covalent attachment of the enzyme in functional groups on the surface and covalent attachment into a linker added post-synthesis. The influence of the immobilization strategy on the enzyme uptake, specific activity, thermal stability, and the possibility of its use through multiple cycles was explored. High specific activities were observed for PPF-2-supported CAL-B in the esterification of oleic acid with ethanol, ranging from 58 to 283 U mg?1, which was 2.6 to 12.7 times greater than the observed for the commercial Novozyme 435.
- Oliveira, Felipe L.,de Souza, Stefania P.,Bassut, Jonathan,álvarez, Heiddy M.,Garcia-Basabe, Yunier,Alves de Souza, Rodrigo O. M.,Esteves, Pierre M.,Gon?alves, Raoni S. B.
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supporting information
p. 15863 - 15870
(2019/11/16)
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- Base-Free Dynamic Kinetic Resolution of Secondary Alcohols with a Ruthenium-Lipase Couple
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We report the dynamic kinetic resolution (DKR) of various secondary alcohols by the combination of a ruthenium catalyst and an anionic surfactant-activated lipoprotein lipase. The DKR reactions performed under totally base-free conditions at room temperature provided the products of excellent enantiopurities (91-99% ee or greater) in high yields (92-99%). More importantly, the DKR of α-arylallyl alcohols was achieved for the first time with high yields (87-91%).
- Yun, Inyeol,Park, Jin Yong,Park, Jaiwook,Kim, Mahn-Joo
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p. 16293 - 16298
(2019/12/27)
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- Stereodivergent Protein Engineering of a Lipase to Access All Possible Stereoisomers of Chiral Esters with Two Stereocenters
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Enzymatic stereodivergent synthesis to access all possible product stereoisomers bearing multiple stereocenters is relatively undeveloped, although enzymes are being increasingly used in both academic and industrial areas. When two stereocenters and thus four stereoisomeric products are involved, obtaining stereodivergent enzyme mutants for individually accessing all four stereoisomers would be ideal. Although significant success has been achieved in directed evolution of enzymes in general, stereodivergent engineering of one enzyme into four highly stereocomplementary variants for obtaining the full complement of stereoisomers bearing multiple stereocenters remains a challenge. Using Candida antarctica lipase B (CALB) as a model, we report the protein engineering of this enzyme into four highly stereocomplementary variants needed for obtaining all four stereoisomers in transesterification reactions between racemic acids and racemic alcohols in organic solvents. By generating and screening less than 25 variants of each isomer, we achieved >90% selectivity for all of the four possible stereoisomers in the model reaction. This difficult feat was accomplished by developing a strategy dubbed "focused rational iterative site-specific mutagenesis" (FRISM) at sites lining the enzyme's binding pocket. The accumulation of single mutations by iterative site-specific mutagenesis using a restricted set of rationally chosen amino acids allows the formation of ultrasmall mutant libraries requiring minimal screening for stereoselectivity. The crystal structure of all stereodivergent CALB variants, flanked by MD simulations, uncovered the source of selectivity.
- Xu, Jian,Cen, Yixin,Singh, Warispreet,Fan, Jiajie,Wu, Lian,Lin, Xianfu,Zhou, Jiahai,Huang, Meilan,Reetz, Manfred T.,Wu, Qi
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supporting information
p. 7934 - 7945
(2019/05/22)
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- Enhancement of activity and reusability of lipase immobilized on magnetic mesoporous silica for the resolution of racemic secondary alcohols
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Magnetic mesoporous silica (MMS) composites with an average mesopore size (~2.98 nm), large surface area (404–442 m2/g), and high saturated magnetization (17.7–33.5 emu/g) were successfully prepared by hydrothermal crystallization in the presence of monodisperse Fe3O4 microspheres. The as-synthesized composites served as supports for lipase from Burkholderia cepacia (BCL) immobilization in isooctane via interfacial activation and were then employed as biocatalysts for the transesterification resolution of racemic aromatic secondary alcohols to synthesize chiral intermediates. The catalytic performance of the immobilized BCL (BCL/MMS) was notably improved compared to that of the non-immobilized BCL, with the total conversion and enantiomeric excess reaching 50 and 99% of the maximum theoretical values, respectively. Furthermore, the magnetic BCL/MMS possessing the same textural properties and enzyme loading exhibited decreasing catalytic capability as their saturated magnetization value increased. Moreover, BCL/MMS could also be readily recycled from the reaction system by applying an external magnetic field so as to facilitate its reuse up to five cycles with retaining up to 90% of the initial activity. Its high activity, easy recovery, and excellent operational stability make the BCL/MMS a potential green catalyst for the synthesis of optically active intermediates.
- Xue, Ping,Hu, Chun-Miao,Yan, Xiang-Hui,Fang, Guo-Li,Shen, Hong-Fang
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p. 427 - 433
(2018/11/25)
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- Highly Focused Library-Based Engineering of Candida antarctica Lipase B with (S)-Selectivity Towards sec-Alcohols
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Candida antarctica lipase B (CALB) is one of the most extensively used biocatalysts in both academia and industry and exhibits remarkable (R)-enantioselectivity for various chiral sec-alcohols. Considering the significance of tailor-made stereoselectivity in organic synthesis, a discovery of enantiocomplementary lipase mutants with high (R)- and (S)-selectivity is valuable and highly desired. Herein, we report a highly efficient directed evolution strategy, using only 4 representative amino acids, namely, alanine (A), leucine (L), lysine (K), tryptophan (W) at each mutated site to create an extremely small library of CALB variants requiring notably less screening. The obtained best mutant with three mutations W104V/A281L/A282K displayed highly reversed (S)-selectivity towards a series of sec-alcohol with E values up to 115 (conv. 50%, ee 94%). Compared with the previously reported (S)-selective CALB variant, W104A, a single mutation provided less selectivity, while the synergistic effects of three mutations in the best variant endow better (S)-selectivity and a broader substrate scope than the W104A variant. Structural analysis and molecular dynamics simulation unveiled the source of reversed enantioselectivity. (Figure presented.).
- Cen, Yixin,Li, Danyang,Xu, Jian,Wu, Qiongsi,Wu, Qi,Lin, Xianfu
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supporting information
p. 126 - 134
(2018/12/05)
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- Enantioselective resolution of (±)-1-phenylethyl acetate by extracellular proteases from deep-sea bacterium Bacillus sp. DL-2
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Chiral 1-phenylethanol and its ester derivative are important chiral chemicals in diverse industries and the preparation of those optically pure enantiomers is of great importance. One bacterium, Bacillus sp. DL-2, whose extracellular proteases could efficiently asymmetrically hydrolyse (±)-1-phenylethyl acetate, was isolated from the deep sea of the Western Pacific. After the immobilization of extracellular proteases and the optimization of enzymatic reactions, (R)-1-phenylethanol was prepared with the enantiomeric excess (e.e.) being 97% and the yield being 41%, respectively. The optimal resolution reaction condition for the preparation of (R)-1-phenylethanol using immobilized extracellular proteases was found to be 5-mM (±)-1-phenylethyl acetate, 360 mg/mL immobilized extracellular proteases, pH 6.5, and 20 °C for 2 h. (S)-1-phenylethyl acetate was generated through enzymatic kinetic resolution with the e.e. being as high as 99% and the yield being 71%, respectively. The optimal resolution reaction condition for the preparation of (S)-1-phenylethyl acetate was found to be 2.5-mM (±)-1-phenylethyl acetate, 440 mg/mL immobilized extracellular proteases, pH 7.5, and 35 °C for 10 h. Our report is the first report about the kinetic resolution of (±)-1-phenylethyl acetate using proteases and the enantio-preference of the proteases was found to be the same as those of most other esterases/lipases. Also notably, the optical purity of (S)-1-phenylethyl acetate generated through kinetic resolution using the proteases of Bacillus sp. DL-2 was the highest report so far. Proteases from deep-sea Bacillus sp. DL-2 are new contributions to the biocatalyst library for the preparation of valuable chiral alcohols and chiral esters through kinetic resolution.
- Dong, Lu,Xu, Yongkai,Zhang, Yun,Sun, Aijun,Hu, Yunfeng
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p. 466 - 478
(2019/06/13)
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- Enzymatic chemical transformations of aldehydes, ketones, esters and alcohols using plant fragments as the only biocatalyst: Ximenia americana grains
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The present study demonstrated the ability of Ximenia american as a biocatalyst in reduction, hydrolysis and esterification reactions. The reduction reactions of aldehydes and ketones, ester hydrolysis and esterification of alcohols were carried out with interesting results. Reduction of ketones afforded yields of 6–60% with ee in the range of 35–>99% and that of aldehydes in yields of 51–99%. On the other hand, ester hydrolysis afforded yields of 58–98% with ee in the range 34–87%, while esterification of alcohols in 18–99% yields. Experimental conditions for all reactions have been defined using standard substrates as indicated in results and discussion. Some of the products are the potential building blocks for the synthesis of molecules which are of pharmaceutical and agrochemical importance.
- da Silva, Romézio Alves Carvalho,de Mesquita, Bruna Marques,de Farias, Iolanda Frota,do Nascimento, Patrícia Georgiana Garcia,de Lemos, Telma Leda Gomes,Queiroz Monte, Francisco José
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p. 187 - 194
(2018/01/05)
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- Structural Investigations on Enantiopure P–OP Ligands: A High-Performing P–OP Ligand for Rhodium-Catalysed Hydrogenations
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A second generation of phosphine–phosphite (P–OP) ligands, incorporating a more sterically bulky phosphite group than previous P–OP ligand designs, gave very efficient catalysts for the Rh-catalysed asymmetric hydrogenation of a diverse array of substrate
- Fernández-Pérez, Héctor,Balakrishna, Bugga,Vidal-Ferran, Anton
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p. 1525 - 1532
(2018/04/20)
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- Expanding the Substrate Specificity of Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase by a Dual Site Mutation
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Here, we report the asymmetric reduction of selected phenyl-ring-containing ketones by various single- and dual-site mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). The further expansion of the size of the substrate binding pocket in the mutant W110A/I86A not only allowed the accommodation of substrates of the single mutants W110A and I86A within the expanded active site but also expanded the substrate range of the enzyme to ketones bearing two sterically demanding groups (bulky–bulky ketones), which are not substrates for the TeSADH single mutants. We also report the regio- and enantioselective reduction of diketones with W110A/I86A TeSADH and single TeSADH mutants. The double mutant exhibited dual stereopreference to generate the Prelog products most of the time and the anti-Prelog products in a few cases.
- Musa, Musa M.,Bsharat, Odey,Karume, Ibrahim,Vieille, Claire,Takahashi, Masateru,Hamdan, Samir M.
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p. 798 - 805
(2018/02/21)
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- Ester Synthesis in Water: Mycobacterium smegmatis Acyl Transferase for Kinetic Resolutions
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The acyl transferase from Mycobacterium smegmatis (MsAcT) catalyses transesterification reactions in aqueous media because of its hydrophobic active site. Aliphatic cyanohydrin and alkyne esters can be synthesised in water with excellent and strikingly opposite enantioselectivity [(R);E>37 and (S);E>100, respectively]. When using this enzyme, the undesired hydrolysis of the acyl donor is an important factor to take into account. Finally, the choice of acyl donor can significantly influence the obtained enantiomeric excesses. (Figure presented.).
- de Leeuw, Nicolas,Torrelo, Guzman,Bisterfeld, Carolin,Resch, Verena,Mestrom, Luuk,Straulino, Emanuele,van der Weel, Laura,Hanefeld, Ulf
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p. 242 - 249
(2017/11/16)
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- Remarkably improved stability and enhanced activity of a: Burkholderia cepacia lipase by coating with a triazolium alkyl-PEG sulfate ionic liquid
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Three types of triazolium cetyl-PEG10 sulfate ionic liquid were synthesized and their activation of Burkholderia cepacia lipase was investigated; both the reaction rate and enantioselectivity depended on the cationic part of the coating ILs and 1-butyl-3-methyl-1,2,3-triazolium cetyl-PEG10 sulfate (Tz1)-coated lipase PS, which is especially suitable for the transesterification of 1-(pyridin-2-yl)ethanol, 1-(pyridin-3-yl)ethanol, and 1-(pyridin-4-yl)ethanol, among 12 types of tested secondary alcohol. The most important result was obtained when these enzymes were stored in an IL ([N221MEM][Tf2N]) solvent: Tz1-PS showed an amazing stability and it exhibited an excellent activity after 2 years when the enzyme was stored in [N221MEM][Tf2N].
- Nishihara,Shiomi,Kadotani,Nokami,Itoh
-
supporting information
p. 5250 - 5256
(2017/11/09)
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- Magnetic Attachment of Lipase Immobilized on Bacteriogenic Iron Oxide Inside a Microtube Reactor for the Kinetic Resolution of Secondary Alcohols
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A PTFE microtube reactor was constructed with lipase immobilized on magnetized bacteriogenic iron oxide, which was retained inside of the tube by attraction to an external magnet. The reactor was used for the lipase-promoted kinetic resolution of secondary alcohols and gave sufficient catalytic activity, which was maintained during long-term flow over 14 days.
- Mandai, Kyoko,Fukuda, Takehiro,Miyazaki, Yuki,Hashimoto, Hideki,Mandai, Hiroki,Ema, Tadashi,Takada, Jun,Suga, Seiji
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supporting information
p. 805 - 810
(2017/04/06)
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- CO2-expanded bio-based liquids as novel solvents for enantioselective biocatalysis
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For the first time, CO2-expanded bio-based liquids were reported as novel and sustainable solvents for biocatalysis. Herein, it was found that by expansion with CO2, 2-methyltetrahydrofuran (MeTHF), and other bio-based liquids, which were not favorable solvents for immobilized Candida antarctica lipase B (Novozym 435) catalyzed transesterification, were tuned into excellent reaction media. Especially, for the kinetic resolution of challenging bulky secondary substrates such as rac-1-adamantylethanol, the lipase displayed very high activity with excellent enantioselectivity (E value > 200) in CO2-expanded MeTHF (MeTHF concentration 10% v/v, 6 MPa), whereas there was almost no activity observed in conventional organic solvents.
- Hoang, Hai Nam,Nagashima, Yoshihiro,Mori, Shuichi,Kagechika, Hiroyuki,Matsuda, Tomoko
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p. 2984 - 2989
(2017/04/26)
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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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- 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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- Dual-Surface Functionalization of Metal-Organic Frameworks for Enhancing the Catalytic Activity of Candida antarctica Lipase B in Polar Organic Media
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One of the most attractive characteristics of metal organic frameworks (MOFs) is their diversity in use as functional materials, because their diversity means that the appropriate MOFs for the required applications can be readily generated from numerous elemental compounds. In addition, post-synthetic modifications of MOFs further expand their diversity. We describe a combined approach involving a typical post-synthetic modification and our previously reported surface modification to introduce multicompounds on MOFs. This method has been used to alter the local environments of a target biocatalyst and has enhanced the activity of the biocatalyst in polar organic media. It has been known that lipases are more active in nonpolar organic solvents than in polar ones. Hence, it can be hypothesized that surrounding lipase molecules with nonpolar compounds possibly increases the activity of lipases in polar organic solvents such as acetonitrile. A series of fatty acids (C12-C22) were conjugated with the amino groups of 2-amino-1,4-benzene dicarboxylate (NH2-BDC) in UiO-66-NH2 (ZrMOF) and then Candida antarctica lipase B (CAL-B) was covalently bonded to the pendent carboxylate groups on the surface of ZrMOF. The introduction of fatty acids around the covalently conjugated CAL-B molecules on ZrMOF improved the activity in acetonitrile by a factor of up to 13.
- Jung, Suhyun,Park, Seongsoon
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p. 438 - 442
(2017/06/05)
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- Dynamic kinetic resolution of aromatic: Sec -alcohols by using a heterogeneous palladium racemization catalyst and lipase
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Microwave-assisted one-pot dynamic kinetic resolution of aromatic secondary alcohols is successfully conducted by using a recyclable chemoenzymatic catalyst combination. This design concept will attract more attention in the foreseeable future for the synthesis of chiral drugs and their building blocks.
- Xu, Yuanfeng,Wang, Meng,Feng, Bo,Li, Ziyang,Li, Yuanhua,Li, Hexing,Li, Hui
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p. 5838 - 5842
(2017/12/26)
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- Immobilization engineering-How to design advanced sol-gel systems for biocatalysis?
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An immobilization engineering approach using bioinformatics and experimental design tools was applied to improve the sol-gel enzyme entrapment methodology. This strategy was used for the immobilization of lipase B from Candida antarctica (CaLB), a versatile enzyme widely used even on the industrial scale. The optimized entrapment of CaLB in sol-gel matrices is reported by the response-surface methodology enabling efficient process development. The immobilized CaLBs characterized by functional efficiency and enhanced recovery provided economical and green options for flow chemistry. Various ternary mixtures of sol-gel precursors allowed the creation of tailored entrapment matrices best suited for the enzyme and its targeted substrate. The sol-gel-entrapped forms of CaLB were excellent biocatalysts in the kinetic resolutions of secondary alcohols and secondary amines with aromatic or aliphatic substituents both in batch and continuous-flow biotransformations.
- Weiser, Diána,Nagy, Flóra,Bánóczi, Gergely,Oláh, Márk,Farkas, Attila,Szilágyi, András,László, Krisztina,Gellért, ákos,Marosi, Gy?rgy,Kemény, Sándor,Poppe, László
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supporting information
p. 3927 - 3937
(2017/08/22)
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- Asymmetric Chemoenzymatic Reductive Acylation of Ketones by a Combined Iron-Catalyzed Hydrogenation–Racemization and Enzymatic Resolution Cascade
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A general and practical process for the conversion of prochiral ketones into the corresponding chiral acetates has been realized. An iron carbonyl complex is reported to catalyze the hydrogenation–dehydrogenation–hydrogenation of prochiral ketones. By merging the iron-catalyzed redox reactions with enantioselective enzymatic acylations a wide range of benzylic, aliphatic and (hetero)aromatic ketones, as well as diketones, were reductively acylated. The corresponding products were isolated with high yields and enantioselectivities. The use of an iron catalyst together with molecular hydrogen as the hydrogen donor and readily available ethyl acetate as acyl donor make this cascade process highly interesting in terms of both economic value and environmental credentials.
- El-Sepelgy, Osama,Brzozowska, Aleksandra,Rueping, Magnus
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p. 1664 - 1668
(2017/04/27)
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- Bidentate Phosphine–Phosphoramidite Ligands of the BettiPhos Family for Rh-Catalyzed Asymmetric Hydrogenation
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Phosphine–phosphoramidites comprising a stereogenic phosphorus atom at the phosphoramidite moiety and a Betti base as chiral backbone have been synthesized. Individual diastereomers have been benchmarked as ligands in the Rh-catalyzed asymmetric hydrogenation of dimethyl itaconate to study the interplay of the different elements of chirality. The privileged diastereomer was applied to Rh-catalyzed asymmetric hydrogenation of several functionalized olefins, leading to high enantioselectivities between 91 and 97 % ee, which confirms the effectiveness of the BettiPhos ligand family in asymmetric catalysis.
- Schmitz, Christian,Holthusen, Katharina,Leitner, Walter,Franciò, Giancarlo
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p. 4111 - 4116
(2017/08/07)
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- Synthesis and application of a novel asymmetric azo reagent: 1-(tert-butyl)-2-(4-chlorobenzyl) azodicarboxylate (tBCAD)
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A series of novel asymmetric azo reagents, 1-(tert-butyl)-2-(4-substituted benzyl) azodicarboxylate, were prepared. The synthetic process has the advantage of simpleness, easy operation, mild reaction condition and high yield. The 1-(tert-butyl)-2-(4-chlorobenzyl) azodicarboxylate (tBCAD) was selected for its stability and convenience to handle, and its precursor can be recycled by recrystallization with toluene. The tBCAD and DIAD were applied to a wide variety of Mitsunobu reactions. The experimental results showed that the performance of tBCAD in Mitsunobu reaction was comparable to that of DIAD, while the stability of tBCAD was much better than DIAD. Thus, tBCAD can be a novel, stable, effective azo-reagent for the Mitsunobu reaction.
- Xie, Jian,Xu, Cai,Dai, Qianjin,Wang, Xiaozhong,Xu, Gang,Chen, Yingqi,Dai, Liyan
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p. 5321 - 5326
(2017/08/04)
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- Chemoenzymatic Dynamic Kinetic Resolution of Secondary Alcohols Using an Air- and Moisture-Stable Iron Racemization Catalyst
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Herein, we report on a metalloenzymatic dynamic kinetic resolution of sec-alcohols employing an iron-based racemization catalyst together with a lipase. The iron catalyst was evaluated in racemization and then used in dynamic kinetic resolution of a numbe
- Gustafson, Karl P. J.,Guemundsson, Arnar,Lewis, Kayla,B?ckvall, Jan-E.
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supporting information
p. 1048 - 1051
(2017/02/05)
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- The effect of the migrating group structure on enantioselectivity in lipase-catalyzed kinetic resolution?of?1-phenylethanol
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We have studied the effects of the acyl moiety on the enantioselectivity of three lipases: Candida antarctica B, Pseudomonas cepacia and Candida cylindracea, frequently used in kinetic resolutions by acylation or hydrolysis. The size of the acyl group was examined using various enol esters during the transesterification of 1-phenylethanol and the hydrolysis of the corresponding phenylethylesters. C. antarctica-B lipase showed the highest selectivity in the transesterification of 1-phenylethanol with isopropenyl and vinyl acetate, vinyl decanoate, vinyl laurate, (E?>?200). The esters 1-phenyl -ethyl-acetate, decanoate and laurate are also hydrolyzed with high selectivities (E?>?150) with CAL-B. The results can be correlated to the three-dimensional form of each lipase. The effect of the migrating group on the reactivity and selectivity of the lipases are discussed for both reactions.
- Melais, Nedjma,Aribi-Zouioueche, Louisa,Riant, Olivier
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p. 971 - 977
(2016/08/08)
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- Bimetallic Nanoshells as Platforms for Metallo- and Biometallo-Catalytic Applications
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The use of gold, silver, platinum and palladium for preparation of bimetallic nanoshells (AgAu, AgPt, and AgPdNSs, respectively) and their use for metallo- and bio-metallo catalytic applications have been described. Bimetallic nanoshells (metallo-catalysts) were employed for silane oxidation to silanols and hydrogen (H2) production. Fast and efficient oxidation of several silanes was observed after only 1 h at room temperature, by employing AgPd NSs as catalyst, acetone as solvent, and water as oxidant. Interestingly, bio-metallo-catalysts (NSs-CALB) prepared from lipase attachment to the bimetallic nanoshells, displayed promising bi-catalytic activities (enzymatic: transesterification; metallic: silane oxidation).
- Kisukuri, Camila M.,Palmeira, Dayvson J.,Rodrigues, Thenner S.,Camargo, Pedro H.C.,Andrade, Leandro H.
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p. 171 - 179
(2016/01/25)
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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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- Merging Iron Catalysis and Biocatalysis—Iron Carbonyl Complexes as Efficient Hydrogen Autotransfer Catalysts in Dynamic Kinetic Resolutions
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A dual catalytic iron/lipase system has been developed and applied in the dynamic kinetic resolution of benzylic and aliphatic secondary alcohols. A detailed study of the Kn?lker-type iron complexes demonstrated the hydrogen autotransfer of alcohols to proceed under mild reaction conditions and allowed the combination with the enzymatic resolution. Different racemic alcohols were efficiently converted to chiral acetates in good yields and with excellent enantioselectivities.
- El-Sepelgy, Osama,Alandini, Nurtalya,Rueping, Magnus
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supporting information
p. 13602 - 13605
(2016/10/21)
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- Immobilization of Candida Antarctica lipase B on epoxy modified silica by sol-gel process
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An epoxy-functionalized silica support was prepared through 3-glycidoxypropyltrimethoxylsilane(KH560)modified silica sol in the presence of triblock copolymer F127 (F-560-S). The surface chemistry, micromorphology and pore structure of the supports were characterized by TG, FTIR, SEM and N2 adsorption-desorption, which showed that the BET surface areas and pore volumes of epoxy-activated supports increased with the addition of F127. The Candida Antarctica Lipase B (CALB) was immobilized on the resulting carrier by covalent link. The lipase absorbed amounts were 58 mg/g support and 375 mg/g support on the normal silica (N-S) and modified silica (F-560-S), respectively. The immobilized lipases were examined as biocatalysts for transesterification of 1-phenethanol and vinyl acetate in nonaqueous medium. Solvents and temperature were investigated for influence of morphology and KH560 on the immobilized lipase. The catalytic activity of the CALB immobilized on F-560-S was improved in various solvents, especially in polar solvents. The immobilized CALBs maintained high activity, while the control experiment using free lipase gave very low ester production in the temperature range of 0-60 °C. Furthermore improved thermal stability of CALB immobilized on F-560-S compared to the CALB on N-S was observed. The CALB immobilized on F-560-S exhibited high operational stability in organic media which still retained 88.3% of its original activity for 12 h consecutive 7 runs.
- Ma, Hong-Zhi,Yu, Xiao-Wei,Song, Cong,Xue, Qing-Lan,Jiang, Bo
-
-
- Tailoring the spacer arm for covalent immobilization of Candida antarctica lipase B - Thermal stabilization by bisepoxide-activated aminoalkyl resins in continuous-flow reactors
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An efficient and easy-to-perform method was developed for immobilization of CaLB on mesoporous aminoalkyl polymer supports by bisepoxide activation. Polyacrylate resins (100-300 μm; ~50 nm pores) with different aminoalkyl functional groups (ethylamine: EA and hexylamine: HA) were modified with bisepoxides differing in the length, rigidity and hydrophobicity of the units linking the two epoxy functions. After immobilization, the different CaLB preparations were evaluated using the lipase-catalyzed kinetic resolution (KR) of racemic 1-phenylethanol (rac-1) in batch mode and in a continuous-flow reactor as well. Catalytic activity, enantiomer selectivity, recyclability, and the mechanical and long-term stability of CaLB immobilized on the various supports were tested. The most active CaLB preparation (on HA-resin activated with 1,6-hexanediol diglycidyl ether - HDGE) retained 90% of its initial activity after 13 consecutive reaction cycles or after 12 month of storage at 4°C. The specific rate (rflow), enantiomer selectivity (E) and enantiomeric excess (ee) achievable with the best immobilized CaLB preparations were studied as a function of temperature in kinetic resolution of rac-1 performed in continuous-flow packed-bed bioreactors. The optimum temperature of the most active HA-HDGE CaLB in continuous-flow mode was 60°C. Although CaLB immobilized on the glycerol diglycidyl ether (GDGE)-activated EA-resin was less active and less selective, a much higher optimum temperature (80°C) was observed with this form in continuous-flow mode KR of rac-1.
- Abaházi, Emese,Lestál, Dávid,Boros, Zoltán,Poppe, László
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- Mechanochemical Enzymatic Kinetic Resolution of Secondary Alcohols under Ball-Milling Conditions
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Mechanosynthesis is a valuable technique, offering attractive alternatives for the preparation of organic, inorganic, and organometallic products. Surprisingly, mechanochemical enzymatic transformations have only scarcely been studied until now. Here, we demonstrate the use of lipase B from Candida antarctica (CALB) in acylative kinetic resolutions of secondary alcohols in mixer and planetary mills. Despite the mechanical stress caused by the high-speed ball milling, the biocatalyst proved highly effective, stable, and, in part, recyclable under the applied mechanochemical conditions. Best milling practice: The compatibility of lipase B from Candida antarctica (CALB) in acylative kinetic resolutions of secondary alcohols in mixer and planetary mills has been explored. Despite the mechanical stress caused by the high-speed ball milling, the biocatalyst was found to be very effective, stable, and, in part, recyclable under the applied mechanochemical conditions.
- Hernández, José G.,Frings, Marcus,Bolm, Carsten
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p. 1769 - 1772
(2016/06/01)
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- The assignment of the configuration for α-hydroxy acid esters using a CEC strategy
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A simple and efficient 1H NMR method for determining the absolute configuration of chiral α-hydroxy acid esters using a competing enantioselective conversion (CEC) strategy was developed. The α-hydroxy acid esters were acylated in the presence
- Peng, Ruixue,Lin, Lili,Zhang, Yuheng,Wu, Wangbin,Lu, Yan,Liu, Xiaohua,Feng, Xiaoming
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p. 5258 - 5262
(2016/07/06)
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