- 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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- 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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- 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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- 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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- Chiral ferrocene-indole diphosphine ligand as well as preparation method and application thereof
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The invention relates to a chiral ferrocene-indole diphosphine ligand as well as a preparation method and application thereof. The specific preparation method comprises the following steps: dissolving an indole compound and a chiral ferrocene phosphine ac
- -
-
Paragraph 0071-0072
(2021/05/22)
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- Chiral ferrocene phosphine-indole aminophosphine ligand as well as preparation method and application thereof
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The invention discloses a chiral ferrocene phosphine-indole aminophosphine ligand as well as a preparation method and application thereof. The preparation method comprises the following steps: dissolving a chiral ferrocene phosphine-indole intermediate in
- -
-
Paragraph 0050-0051
(2021/05/22)
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- Development of environmentally friendly lipase-catalysed kinetic resolution of (R,S)-1-phenylethyl acetate using aqueous natural deep eutectic solvents
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Over the past decade, natural deep eutectic solvents (NADES) have become promising green solvent from both environmental and technological perspectives. The number of structural combinations encompassed by NADES is tremendous; thus, NADES with unique physicochemical properties can be designed for a particular purpose, such as for efficient biocatalytic processes. The aim of this work was to prepare several NADES based on renewable sources (biomass energy) and to apply these solvents in the industrially interesting process of lipase-catalysed (R)-1-phenylethanol synthesis. Based on experimental data on lipase behaviour in the tested NADES, choline chloride:glycerol (ChGly) was selected as the most promising solvent for the given reaction. The resulting (R)-1-phenylethanol was also successfully isolated and purified from the reaction mixture using liquid-liquid extraction with ethyl acetate, whilst ChGly was recycled and reused. (R)-1-phenylethanol and unreacted (S)-1-phenylethyl acetate were purified on silica gel columns with yields of 81.91 %. The biocatalyst was also successfully recycled and reused in 4 cycles. Based on laboratory-scale optimum conditions, (R)-1-phenylethanol synthesis performed in a 500 mL batch reactor achieved reaction conversions comparable to those obtained with millilitre-scale biocatalytic reactions. The downstream process was also performed on a preparative scale with a yield of 49.48 %.
- Cvjetko Bubalo, Marina,Jurinjak Tu?ek, Ana,Maros, Izabela,Pani?, Manuela,Radoj?i? Redovnikovi?, Ivana,Radovi?, Mia
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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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- 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-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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- 18O-Labeled chiral compounds enable the facile determination of enantioselectivity by mass spectroscopy
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The synthesis of 18O-labeled enantioenriched compounds and their facile evaluation system to determine enantiomeric excess (ee) using mass spectroscopy was described. Equimolar mixture of 18O-labeled and non-labeled pseudo-enantiomers were used as a substrate for enzyme-catalyzed kinetic resolution. Ees determined by mass spectroscopy showed good agreement with those by HPLC. Our method would be a promising tool for fast evaluation of ee and contribute to development of enantioselective transformations.
- Mandai, Kyoko,Tsuchihashi, Yuta,Ashikari, Yosuke,Yoshida, Jun-ichi,Nagaki, Aiichiro
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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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- 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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- 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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- 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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- Benzoate Surfactants for Enhancing the Activity of Lipoprotein Lipase from Burkholderia Species in Organic Solvent
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Two benzoate surfactants were synthesized and examined as the additives for enhancing the activity of a lipoprotein lipase from Burkholderia species (BSLPL) in organic solvent. It was found that the benzoate surfactants enhanced the turnover number (kcat) by four orders of magnitude and the catalytic efficiency (kcat/Km) by three orders of magnitude. These results strongly suggest that the favorable interaction between the aromatic rings of surfactant tails and the hydrophobic residues around the active site of enzyme may help BSLPL maintain highly active open conformation in organic solvent.
- Oh, Yeonock
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p. 1093 - 1097
(2019/11/05)
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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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- 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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p. 1876 - 1884
(2018/09/04)
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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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- Pore Environment Control and Enhanced Performance of Enzymes Infiltrated in Covalent Organic Frameworks
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In the drive toward green and sustainable methodologies for chemicals manufacturing, biocatalysts are predicted to have much to offer in the years to come. That being said, their practical applications are often hampered by a lack of long-term operational stability, limited operating range, and a low recyclability for the enzymes utilized. Herein, we show how covalent organic frameworks (COFs) possess all the necessary requirements needed to serve as ideal host materials for enzymes. The resultant biocomposites of this study have shown the ability boost the stability and robustness of the enzyme in question, namely lipase PS, while also displaying activities far outperforming the free enzyme and biocomposites made from other types of porous materials, such as mesoporous silica and metal-organic frameworks, exemplified in the kinetic resolution of the alcohol assays performed. The ability to easily tune the pore environment of a COF using monomers bearing specific functional groups can improve its compatibility with a given enzyme. As a result, the orientation of the enzyme active site can be modulated through designed interactions between both components, thus improving the enzymatic activity of the biocomposites. Moreover, in comparison with their amorphous analogues, the well-defined COF pore channels not only make the accommodated enzymes more accessible to the reagents but also serve as stronger shields to safeguard the enzymes from deactivation, as evidenced by superior activities and tolerance to harsh environments. The amenability of COFs, along with our increasing understanding of the design rules for stabilizing enzymes in an accessible fashion, gives great promise for providing "off the shelf" biocatalysts for synthetic transformations.
- Sun, Qi,Fu, Chung-Wei,Aguila, Briana,Perman, Jason,Wang, Sai,Huang, Hsi-Ya,Xiao, Feng-Shou,Ma, Shengqian
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supporting information
p. 984 - 992
(2018/02/07)
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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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- 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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- 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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- 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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- 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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- Kinetic resolution of secondary carbinols by a chiral N,N-4-dimethylaminopyridine derivative containing a 1,1′-binaphthyl unit: Hydrogen bonding affects catalytic activity and enantioselectivity
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We developed an acylative kinetic resolution of secondary carbinols using a binaphthyl-based N,N-4-dimethylaminopyridine (DMAP) derivative 1d with tert-Alcohol substituents. The reaction proceeded with a wide range of carbinols with moderate to high selectivity (s) (up to s = 79.5). Kinetic studies revealed that catalyst 1d was more catalytically active than the corresponding bis-methyl ether 1d′ or DMAP. Hydrogen bonding between tert-Alcohols of the catalyst and secondary carbinols was responsible for the enhanced reaction rate and high enantioselectivity.
- Fujii, Kazuki,Mitsudo, Koichi,Mandai, Hiroki,Suga, Seiji
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p. 1081 - 1092
(2016/10/11)
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- Removing the Active-Site Flap in LipaseA from Candida antarctica Produces a Functional Enzyme without Interfacial Activation
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A mobile region is proposed to be a flap that covers the active site of Candida antarctica lipaseA. Removal of the mobile region retains the functional properties of the enzyme. Interestingly interfacial activation, required for the wild-type enzyme, was not observed for the truncated variant, although stability, activity, and stereoselectivity were very similar for the wild-type and variant enzymes. The variant followed classical Michaelis-Menten kinetics, unlike the wild type. Both gave the same relative specificity in the transacylation of a primary and a secondary alcohol in organic solvent. Furthermore, both showed the same enantioselectivity in transacylation of alcohols and the hydrolysis of alcohol esters, as well as in the hydrolysis of esters chiral at the acid part.
- Wikmark, Ylva,Engelmarkcassimjee, Karim,Lihammar, Richard,B?ckvall, Jan-E.
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p. 141 - 145
(2016/01/26)
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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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- Immobilization and characterization of a new regioselective and enantioselective lipase obtained from a metagenomic library
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In previous work, a new lipase and its cognate foldase were identified and isolated from a metagenomic library constructed from soil samples contaminated with fat. This new lipase, called LipG9, is a true lipase that shows specific activities that are comparable to those of well-known industrially-used lipases with high activity against long-chain triglycerides. In the present work, LipG9 was co-expressed and co-immobilized with its foldase, on an inert hydrophobic support (Accurel MP1000). We studied the performance of this immobilized LipG9 (Im-LipG9) in organic media, in order to evaluate its potential for use in biocatalysis. Im-LipG9 showed good stability, maintaining a residual activity of more than 70% at 50°C after incubation in n-heptane (log P 4.0) for 8 h. It was also stable in polar organic solvents such as ethanol (log P -0.23) and acetone (log P -0.31), maintaining more than 80% of its original activity after 8 h incubation at 30°C. The synthesis of ethyl esters was tested with fatty acids of different chain lengths in n-heptane at 30°C. The best conversions (90% in 3 h) were obtained for medium and long chain saturated fatty acids (C8, C14 and C16), with the maximum specific activity, 29 U per gram of immobilized preparation, being obtained with palmitic acid (C16). Im-LipG9 was sn-1,3-specific. In the transesterification of the alcohol (R,S)-1-phenylethanol with vinyl acetate and the hydrolysis of the analogous ester, (R, S)-1-phenylethyl acetate, Im-LipG9 showed excellent enantioselectivity for the R-isomer of both substrates (E> 200), giving an enantiomeric excess (ee) of higher than 95% for the products at 49% conversion. The results obtained in this work provide the basis for the development of applications of LipG9 in biocatalysis.
- Alnoch, Robson Carlos,Martini, Viviane Paula,Glogauer, Arnaldo,Costa, Allen Carolina Dos Santos,Piovan, Leandro,Muller-Santos, Marcelo,De Souza, Emanuel Maltempi,Pedrosa, Fábio De Oliveira,Mitchell, David Alexander,Krieger, Nadia
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- Substrate specificity of an esterase from the archaeon Sulfolobus tokodaii bearing a GGG(A)X motif
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A GGG(A)X-type esterase (Est0071) from an archaeon catalyzes asymmetric hydrolysis of prochiral bulky malonic diesters in good enantioselectivity. The selectivity of Est0071 was for the opposite enantiomer to that previously shown for pig liver esterase, and the resulting enantiomeric excess of the products was higher. Est0071 could also catalyze the hydrolysis of various acetates of secondary alcohols, and showed moderate enantioselectivity in these reactions.
- Wada, Reina,Ozaki, Masanaru,Kumon, Takashi,Ohta, Hiromichi,Miyamoto, Kenji
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p. 188 - 190
(2015/11/09)
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- Kinetic resolution of secondary alcohols with Burkholderia cepacia lipase immobilized on a biodegradable ternary blend polymer matrix as a highly efficient and heterogeneous recyclable biocatalyst
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The present work reports a highly efficient and biocatalytic heterogeneous protocol for kinetic resolution (KR) of racemic secondary alcohols with vinyl acetate as an acyl donor, using the biocatalyst Burkholderia cepacia lipase (BCL) immobilized on a biodegradable ternary blend support through polylactic acid (PLA)/polyvinyl alcohol (PVA)/chitosan (CHI); (PLA/PVA/CHI-BCL). The KR reaction with various substituted aromatic, heterocyclic racemic secondary alcohols gave enantiomerically pure alcohol and its enantioenriched acetate derivatives with high conversion (45-50%) and excellent enantiomeric excess (up to 99% ee) at optimized reaction conditions. The reaction works under mild conditions using simple and inexpensive starting materials such as racemic alcohols, vinyl acetate, and immobilized biocatalyst. The given protocol provides excellent recyclability with good yield and enantiomeric excess values up to the studied range of five cycles. The resultant products were characterized with the help of different analytical techniques such as 1H and 13C-NMR, chiral HPLC column, polarimeter, IR and GC-MS.
- More, Ganesh V.,Badgujar, Kirtikumar C.,Bhanage, Bhalchandra M.
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p. 4592 - 4598
(2015/02/19)
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- CAL-B-Catalyzed Enantioselective Deacetylation of Some Benzylic Acetate Derivatives Via Alcoholysis in Non-aqueous Media
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Enantioselective deacetylation of a set of benzylic acetates via alcoholysis catalyzed by Lipase B from Candida antarctica (CAL-B), under mild conditions is described. A systematic study allows to determine the appropriate combination nucleophile/organic solvent and also to explain the influence of these parameters on the enzymatic catalytic reaction. In all cases, (R)-alcohols are obtained with high ee (up to >99 %) at conversion 36 % 500. The enzymatic reactivity is influenced by the hydrophobicity of solvent and the structure/nature of the nucleophile. Furthermore, CAL-B allows enantio-complementary between transesterifications in non-aqueous media: alcoholysis and acetylation.
- Zadi, Amna,Merabet-Khelassi, Mounia,Aribi-Zouioueche, Louisa
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p. 1054 - 1061
(2015/02/05)
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- Selectivity Enhancement in Dynamic Kinetic Resolution of Secondary Alcohols through Adjusting the Micro-Environment of Metal Complex Confined in Nanochannels: A Promising Strategy for Tandem Reactions
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(Figure Presented). Dichloro(η6-p-cymene) (1-butyl-3-cyclohexyl-imidazolin-2-ylidene) ruthenium(II) (RuL) was synthesized and confirmed. Five heterogeneous catalysts with similar ruthenium cores were prepared by chemical immobilization method using various silica-based supports, including mesoporous silica SBA-15 of different pore sizes (Ru/Si-9, Ru/Si-8, and Ru/Si-7), nonporous silica particles (Ru/SiO2), and surface trimethylsilylated SBA-15 (Ru/SiMe). The dynamic kinetic resolution (DKR) of 1-phenylethanol, which includes metal-enzyme bicatalytic racemization in tandem with stereoselective acylation, gave product in 99% yield and 0% ee with homogeneous catalyst RuL, whereas the heterogeneous Ru/Si-8 exhibited high catalytic activity and enantioselectivity (up to 96% yield and 99% ee). The racemization and acylation abilities of different catalysts were analyzed. The influences of pore size and surface properties for heterogeneous catalysts were investigated, and the nanocage effect was found to be the key factor in stereoselectivity. The catalyst Ru/Si-8 performed well in reactions with various substrates and can be reused for at least seven times.
- Cao, Hui,Zhu, Xiao-Han,Wang, Dong,Sun, Zhenkun,Deng, Yonghui,Hou, Xiu-Feng,Zhao, Dongyuan
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- Chemical modification of lipase for rational enhancement of enantioselectivity
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Chemical modifications of the I287C mutant of a Burkholderia cepacia lipase afforded various I287C-X conjugates, among which I287C-PAA bearing an N-phenylacetamide (PAA) moiety showed excellent enantioselectivity and catalytic activity for secondary alcohols. Site-directed chemical modifications are powerful tools to control enantioselective biocatalysis.
- Ema, Tadashi,Inoue, Hiroki
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supporting information
p. 1374 - 1376
(2015/11/24)
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- 1,1-P-OP ligands with P-stereogenic phosphino groups in asymmetric hydrogenations and hydroformylations
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A new series of narrow-bite-angle phosphine-phosphite (1,1-P-OP) ligands (3a-d) has been efficiently prepared from the enantiopure (SP)-tert- butyl(hydroxymethyl)methylphosphino borane complex 1, a crucial intermediate. The catalytic performance of the ligands in Rh-mediated asymmetric hydrogenations and hydroformylations is described. The corresponding rhodium complexes provided excellent efficiencies (full conversion in all cases) and high enantioselectivities (up to 98% ee) for the asymmetric hydrogenation of structurally diverse functionalized alkenes. Furthermore, rhodium catalysts derived from these 1,1-P-OP ligands were highly active and gave excellent regioselectivities (branched/linear product ratios of up to 97/3) and moderate enantioselectivities in the hydroformylation of different terminal olefins.
- Lao, Joan R.,Benet-Buchholz,Vidal-Ferran, Anton
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p. 2960 - 2963
(2014/07/08)
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- Enantiopure narrow bite-angle P-OP ligands: Synthesis and catalytic performance in asymmetric hydroformylations and hydrogenations
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Herein is reported the preparation of a set of narrow bite-angle P-OP ligands the backbone of which contains a stereogenic carbon atom. The synthesis was based on a Corey-Bakshi-Shibata (CBS)-catalyzed asymmetric reduction of phosphomides. The structure of the resulting 1,1-P-OP ligands, which was selectively tuned through adequate combination of the configuration of the stereogenic carbon atom, its substituent, and the phosphite fragment, proved crucial for providing a rigid environment around the metal center, as evidenced by X-ray crystallography. These new ligands enabled very good catalytic properties in the Rh-mediated enantioselective hydrogenation and hydroformylation of challenging and model substrates (up to 99 % ee). Whereas for asymmetric hydrogenation the optimal P-OP ligand depended on the substrate, for hydroformylation, a single ligand was the highest-performing one for almost all studied substrates: it contains an R-configured stereogenic carbon atom between the two phosphorus ligating groups, and an S-configured 3,3′-diphenyl-substituted biaryl unit. Ligand design: Narrow-bite-angle P-OP ligands incorporating a stereogenic carbon atom in their backbone have been synthesized by Corey-Bakshi-Shibata (CBS)-catalyzed asymmetric reduction of the corresponding intermediates followed by O-phosphorylation. Rhodium complexes of these ligands provided very good catalytic performance in hydroformylations and hydrogenations (see scheme).
- Fernández-Pérez, Héctor,Benet-Buchholz, Jordi,Vidal-Ferran, Anton
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p. 15375 - 15384
(2016/02/18)
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- Structure-activity relationship of dihydroimidazo-, dihydropyrimido, tetrahydrodiazepino-[2,1-b]-thiazoles, and -benzothiazoles as an acylation catalyst
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Cyclic isothioureas 1, 2, 3, and 4 were synthesized through a four-step procedure from the corresponding ortho-bromoanilines 10 via Pd- or Cu-catalyzed cyclization-benzothiazole formation. Nonbenzo analogues 7, 8, and 9 were synthesized by a condensation reaction of cyclic thioureas 15 and α-bromoacetophenones 14. Investigations of the acylation reactions of 1-phenylethanol with acid anhydrides in the presence of these cyclic isothiourea catalysts revealed their structure-activity relationships. Remarkable electronic effects resulting from substituent(s) on a benzo or phenyl moiety and the influence of the size of the annulating ring were observed. Introduction of an electron-donating substituent(s) enhanced the reaction rate. A few substitution effects on chiral catalysts of type 3 and 7 were also studied.
- Okamoto, Sentaro,Sakai, Yuzo,Watanabe, Saki,Nishi, Shohei,Yoneyama, Aya,Katsumata, Hitomi,Kosaki, Yu,Sato, Rumi,Shiratori, Megumi,Shibuno, Misuzu,Shishido, Tsukasa
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p. 1909 - 1912
(2014/03/21)
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- Dynamic double kinetic resolution of amines and alcohols under the cocatalysis of Raney nickel/Candida antarctica lipase B: From concept to application
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Herein, we have established a dynamic double kinetic resolution (DDKR) strategy under the co-catalysis of Raney nickel and Candida antarctica lipase B (CAL-B) for the one-pot simultaneous resolution of primary amines and secondary alcohols (or esters). The DDKR strategy was successfully applied to the resolution of a series of racemic amines and secondary alcohols (or esters) as well as mexiletine, an important antiarrhythmic agent. The catalysts could be recycled and reused several times with the same high activity. Scale-up experiments were also successful. As a more atom-economical and efficient process than traditional simple kinetic resolutions, the DDKR strategy can be widely used to prepare optically pure amines and alcohols.
- Xia, Bo,Cheng, Guilin,Lin, Xianfu,Wu, Qi
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p. 2917 - 2923
(2014/05/20)
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- Lipase activity and enantioselectivity of whole cells from a wild-type Aspergillius flavus strain
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This study reports the high enantiomeric preference of whole cell lipase from Aspergillus flavus wild-type that allows the preparation of a chiral secondary alcohol. Whole cells prepared from a wild-type Aspergillus flavus strain were used as biocatalysts to prepare (R)-1-phenylethyl acetate. (R)-1-Phenylethanol was esterified into (R)-1-phenylethyl acetate with a 94.6% enantiomeric excess (ee) within 24 h at 40 C and (S)-1-phenylethanol remained in the reaction medium with a >99%ee. Besides, this biocatalyst allows the preparation of ethyl laurate and a mixture of 2-chloro-1-(chloromethyl)ethyl acrylate and 2,3-dichloro-1-propyl acrylate. The ethyl laurate yield was 96%, whereas the synthesis of a mixture of the acrylate regioisomers, 2-chloro-1-(chloromethyl)ethyl acrylate and 2,3-dichloro-1-propyl acrylate gave similar yields to those obtained using commercial lipases.
- Solarte, Carmen,Yara-Varon, Edinson,Eras, Jordi,Torres, Merce,Balcells, Merce,Canela-Garayoa, Ramon
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- Enhancement of (stereo)selectivity in dynamic kinetic resolution using a core-shell nanozeolite@enzyme as a bi-functional catalyst
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A core-shell nanozeolite@enzyme bi-functional catalyst is constructed, which greatly improves selectivity and stereoselectivity of products in dynamic kinetic resolution of aromatic secondary alcohols compared with mixed catalysts, especially those involving small acyl donors. This journal is the Partner Organisations 2014.
- Wang, Wanlu,Li, Xiang,Wang, Zhoujun,Tang, Yi,Zhang, Yahong
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supporting information
p. 9501 - 9504
(2014/08/18)
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- Molecular design exploiting a fluorine gauche effect as a stereoelectronic trigger
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Acyclic conformational control often relies on destabilising noncovalent interactions to give rise to predictable conformer populations. Pertinent examples of such strategies include allylic strain (A1,2 and A 1,3) and syn-pentane interactions. However, the incorporation of fluorine vicinal to an electron-withdrawing group (F-Cβ-C α-X) can lead to predictable conformations as a consequence of stabilising hyperconjugative and/or electrostatic interactions. Herein, we describe the application of a fluorine gauche effect to predictably control torsional rotation in a class of fluorinated 4-(dimethylamino)pyridine (DMAP) analogues. Intramolecularisation, such as protonation or acylation, generates an electropositive nitrogen centre vicinal to the fluorine atom at a molecular hinge (F-Cβ-Cα-N+); this is the only rotatable sp3-sp3 bond. In so doing, this substrate binding triggers a conformational change akin to the induced fit process inherent to enzymatic systems. Herein, we validate this design approach to control molecular space. A number of X-ray structures are documented that display this gauche preference (φNCCF ≈ 60°). Preliminary catalysis experiments are disclosed together with a kinetic and reactivity analysis. The fluorine gauche effect was used to control torsional rotation in fluorinated dimethylamino pyridine (DMAP) analogues. Upon substrate binding an electropositive nitrogen centre vicinal to the fluorine atom at a molecular hinge (F-Cβ-Cα-N+) triggers a conformational change akin to those induced in enzymatic systems. Catalysis experiments and kinetic and reactivity studies are disclosed. Copyright
- Rey, Yannick P.,Zimmer, Lucie E.,Sparr, Christof,Tanzer, Eva-Maria,Schweizer, W. Bernd,Senn, Hans Martin,Lakhdar, Sami,Gilmour, Ryan
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p. 1202 - 1211
(2014/03/21)
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- Molecular Design Exploiting a Fluorine gauche Effect as a Stereoelectronic Trigger
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Acyclic conformational control often relies on destabilising noncovalent interactions to give rise to predictable conformer populations. Pertinent examples of such strategies include allylic strain (A1,2 and A1,3) and syn-pentane interactions. However, the incorporation of fluorine vicinal to an electron-withdrawing group (F-Cβ-Cα-X) can lead to predictable conformations as a consequence of stabilising hyperconjugative and/or electrostatic interactions. Herein, we describe the application of a fluorine gauche effect to predictably control torsional rotation in a class of fluorinated 4-(dimethylamino)pyridine (DMAP) analogues. Intramolecularisation, such as protonation or acylation, generates an electropositive nitrogen centre vicinal to the fluorine atom at a molecular hinge (F-Cβ-Cα-N+); this is the only rotatable sp3-sp3 bond. In so doing, this "substrate binding" triggers a conformational change akin to the induced fit process inherent to enzymatic systems. Herein, we validate this design approach to control molecular space. A number of X-ray structures are documented that display this gauche preference (φNCCF ≈ 60). Preliminary catalysis experiments are disclosed together with a kinetic and reactivity analysis.
- Rey, Yannick P.,Zimmer, Lucie E.,Sparr, Christof,Tanzer, Eva-Maria,Schweizer, W. Bernd,Senn, Hans Martin,Lakhdar, Sami,Gilmour, Ryan
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supporting information
p. 1202 - 1211
(2015/10/05)
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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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- A green route to enantioenriched (S)-arylalkyl carbinols by deracemization via combined lipase alkaline-hydrolysis/Mitsunobu esterification
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Herein we report results of the chemoenzymatic deracemization of a range of secondary benzylic acetates 1a-9a via a sequence of hydrolysis with CAL-B lipase in non-conventional media, combined with esterification of the recovered alcohol according to the Mitsunobu protocol following an enzymatic kinetic resolution (KR). The KR of racemic acetates 1a-9a via an enzymatic hydrolysis, with CAL-B lipase and Na2CO3, in non-aqueous media was optimized and gave high selectivities (E ? 200) at good conversions (C >49%) for all of the substrates studied. This method competes well with the traditional one performed in a phosphate buffer solution. The deracemization using Mitsunobu inversion gave the (S)-acetates in moderate to excellent enantiomeric excess 75% ee 99%, in acceptable isolated yields 70% yield 89%, and with some variations according to the acetate structure.
- Houiene, Zahia,Merabet-Khelassi, Mounia,Bouzemi, Nassima,Riant, Olivier,Aribi-Zouioueche, Louisa
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p. 290 - 296
(2013/04/23)
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- Highly enantioselective Rh-catalysed hydrogenation of 1-alkyl vinyl esters using phosphine-phosphoramidite ligands
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MatPhos, a good mate for hard tasks: The asymmetric hydrogenation of 1-alkyl vinyl esters, thwarted so far by mediocre ee values and low activities, can now be achieved with MatPhos/Rh catalysts with ee values of 96-99 % for a variety of substrates at low catalyst loadings (0.1-1 mol %) and under mild conditions (5-20 bar H2, room temperature). After hydrolysis, the corresponding chiral secondary alkyl alcohols can be obtained in high enantiopurities providing a general and practical route to this important product class. Copyright
- Konrad, Tina Maria,Schmitz, Pascal,Leitner, Walter,Francio, Giancarlo
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supporting information
p. 13299 - 13303
(2013/10/08)
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- Direct formation of tethered Ru(II) catalysts using arene exchange
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An 'arene exchange' approach has been successfully applied for the first time to the synthesis of Ru(II)-based 'tethered' reduction catalysts directly from their ligands in one step. This provides an alternative method for the formation of known complexes, and a route to a series of novel complexes. The novel complexes are highly active in both asymmetric transfer and pressure hydrogenation of ketones.
- Soni, Rina,Jolley, Katherine E.,Clarkson, Guy J.,Wills, Martin
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supporting information
p. 5110 - 5113
(2013/10/22)
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- Elucidating absolute configuration of unsaturated alcohols via enantioselective acylation reactions
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Enantioselective nucleophilic acylation catalysis provides a simple method of determining absolute configuration for unsaturated alcohols. Extension of this technique to natural products and synthetic compounds, as well as current limitations of this appr
- Legay, Christina M.,Boudreau, Colton G.,Derksen, Darren J.
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p. 3432 - 3435
(2013/06/26)
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- Laboratory evolution of enantiocomplementary Candida antarctica lipase B mutants with broad substrate scope
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Candida antarctica lipase B (CALB) is a robust and easily expressed enzyme used widely in academic and industrial laboratories with many different kinds of applications. In fine chemicals production, examples include acylating kinetic resolution of racemic secondary alcohols and amines as well as desymmetrization of prochiral diols (or the reverse hydrolytic reactions). However, in the case of hydrolytic kinetic resolution of esters or esterifying kinetic resolution of acids in which chirality resides in the carboxylic acid part of the substrate, rate and stereoselectivity are generally poor. In the present study, directed evolution based on iterative saturation mutagenesis was applied to solve the latter problem. Mutants with highly improved activity and enantioselectivity relative to wild-type CALB were evolved for the hydrolytic kinetic resolution of p-nitrophenyl 2-phenylpropanoate, with the selectivity factor increasing from E = 1.2 (S) to E = 72 (S) or reverting to E = 42 (R) on an optional basis. Surprisingly, point mutations both in the acyl and alcohol pockets of CALB proved to be necessary. Some of the evolved CALB mutants are also efficient biocatalysts in the kinetic resolution of other chiral esters without performing new mutagenesis experiments. Another noteworthy result concerns the finding that enantiocomplementary CALB mutants for α-substituted carboxylic acid esters also show stereocomplementarity in the hydrolytic kinetic resolution of esters derived from chiral secondary alcohols. Insight into the source of stereoselectivity was gained by molecular dynamics simulations and docking experiments.
- Wu, Qi,Soni, Pankaj,Reetz, Manfred T.
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supporting information
p. 1872 - 1881
(2013/08/24)
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- Separation of enantiopure m-substituted 1-phenylethanols in high space-time yield using Bacillus subtilis esterase
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A recombinant Bacillus subtilis esterase (BsE) expressed in E. coli was found to exhibit excellent enantioselectivity (E was always greater than 100) towards m-substituted 1-phenylethanol acetates in the enantioselective hydrolysis reaction. An explanation for the high enantioselectivity observed towards these substrates was provided by molecular modeling. Moreover, the BsE also showed strong tolerance towards a high concentration of m-substituted 1-phenylethanol acetates (up to 1 M). Based on these excellent catalytic properties of BsE, a kind of m-substituted 1-phenylethanols, (R)-1-(3-chlorophenyl)ethanol, was efficiently synthesized in space-time yield of 920 g per L per day and 97% ee, indicating that the BsE was considered as a potentially ideal and promising biocatalyst for large-scale production of optically active m-substituted 1-phenylethanols. The Royal Society of Chemistry 2013.
- Zheng, Gao-Wei,Liu, Xu-Yun,Zhang, Zhi-Jun,Tian, Ping,Lin, Guo-Qiang,Xu, Jian-He
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p. 20446 - 20449
(2013/11/06)
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- Kinetic resolution of secondary alcohols by chiral dmap derivatives prepared by the Ugi multicomponent reaction
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The kinetic resolution of secondary alcohols was examined by new chiral DMAP derivatives, which can readily be prepared by the Ugi multicomponent reaction in a one-pot operation. The initial screening of DMAP derivatives indicated that the catalyst bearing L-valine with an S configuration at the a-position of amide showed the best stereoselectivity factor. After the reaction conditions were optimized with (S,S)-4a in the kinetic resolution of secondary alcohols, various acyclic and cyclic secondary alcohols could be resolved with an s -factor of up to 12.
- Mandai, Hiroki,Irie, Shunsuke,Akehi, Masaru,Yuri, Kazunobu,Yoden, Masaaki,Mitsudo, Koichi,Suga, Seiji
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p. 329 - 340
(2013/03/28)
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