- 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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- Improved Enantioselectivity of Subtilisin Carlsberg towards Secondary Alcohols by Protein Engineering
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Generally, the catalytic activity of subtilisin Carlsberg (SC) for transacylation reactions with secondary alcohols in organic solvent is low. Enzyme immobilization and protein engineering was performed to improve the enantioselectivity of SC towards secondary alcohols. Possible amino-acid residues for mutagenesis were found by combining available literature data with molecular modeling. SC variants were created by site-directed mutagenesis and were evaluated for a model transacylation reaction containing 1-phenylethanol in THF. Variants showing high E values (>100) were found. However, the conversions were still low. A second mutation was made, and both the E values and conversions were increased. Relative to that shown by the wild type, the most successful variant, G165L/M221F, showed increased conversion (up to 36 %), enantioselectivity (E values up to 400), substrate scope, and stability in THF.
- Dorau, Robin,G?rbe, Tamás,Svedendahl Humble, Maria
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p. 338 - 346
(2017/12/26)
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- Efficient O-Acylation of Alcohols and Phenol Using Cp2TiCl as a Reaction Promoter
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A method has been developed for the conversion of primary, secondary, and tertiary alcohols, and phenol, into the corresponding esters at room temperature. The method uses a titanium(III) species generated from a substoichiometric amount of titanocene dichloride together with manganese(0) as a reductant, as well as methylene diiodide. It involves a transesterification from an ethyl ester, or a reaction with an acyl chloride. A radical mechanism is proposed for these transformations.
- Durán-Pe?a, María Jesús,Botubol-Ares, José Manuel,Hanson, James R.,Hernández-Galán, Rosario,Collado, Isidro G.
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supporting information
p. 3584 - 3591
(2016/07/28)
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- An extremely efficient and green method for the acylation of secondary alcohols, phenols and naphthols with a deep eutectic solvent as the catalyst
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The typical deep eutectic solvent [CholineCl][ZnCl2]3, easily prepared from choline chloride and zinc chloride, is green and useful for the acylation of secondary alcohols, phenols, and naphthols with acid anhydrides. Its efficiency allows the acylation of sterically hindered secondary alcohols and acid anhydrides to proceed in high yield under mild condition. The catalyst is cheap, easy to handle, conveniently synthesized in a single step, and recyclable for several times without significant loss of catalytic activity.
- Nguyen, Hai Truong,Tran, Phuong Hoang
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p. 98365 - 98368
(2016/10/31)
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- 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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- Functionalized organocatalytic nanoreactors: Hydrophobic pockets for acylation reactions in water
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The effect of covalently attaching 4-(dimethylamino)pyridine (DMAP) functionality to the hydrophobic core of a polymeric micelle in water has been investigated in the context of acylation reactions employing non-water-soluble substrates. For this purpose a novel temperature-responsive polymeric micelle has been synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization techniques. The reactivity of the tethered organocatalyst within the nanostructure was found to be extremely high, improving in some cases the acylation rates up to 100 times compared to those for unsupported DMAP in organic solvents. Moreover, the catalytic nanoreactors have been demonstrated to be capable of reuse up to 6 times while maintaining high activity.
- Cotanda, Pepa,Lu, Annhelen,Patterson, Joseph P.,Petzetakis, Nikos,O'Reilly, Rachel K.
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scheme or table
p. 2377 - 2384
(2012/06/29)
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- Molecular recognition driven catalysis using polymeric nanoreactors
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The concept of using polymeric micelles to catalyze organic reactions in water is presented and compared to surfactant based micelles in the context of molecular recognition. We report for the first time enzyme-like specific catalysis by tethering the catalyst in the well-defined hydrophobic core of a polymeric micelle.
- Cotanda, Pepa,O'Reilly, Rachel K.
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supporting information
p. 10280 - 10282,3
(2020/09/09)
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- Dynamic kinetic resolution of secondary aromatic alcohols with new efficient acyl donors
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A new and efficient dynamic kinetic resolution (DKR) process of secondary aromatic alcohols by using long carbon-chain esters as acyl donors has been developed. During the process, the transesterification catalyzed by CD8604 was found to be the main reason for the decrease in enantiomeric excess (ee). Using complex acyl donors, such as 4-chlorophenyl valerate, we could effectively inhibit the resin-catalyzed transesterification, and an excellent ee value (>99%) at high yield (>99%) was achieved. The mechanism for the inhibition of resin-catalyzed transesterification is believed to be the formation of micro-micelles in the pores of CD8604. It is noteworthy that the system can be reused more than 20 times without a loss of yield or ee value.
- Xu, Gang,Chen, Yongjun,Wu, Jianping,Cheng, Yongmei,Yang, Lirong
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experimental part
p. 1373 - 1378
(2011/11/06)
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- Ruthenium pincer-catalyzed acylation of alcohols using esters with liberation of hydrogen under neutral conditions
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Acylation of secondary alcohols using non-activated esters, in particular symmetrical esters (such as ethyl acetate), is achieved under neutral conditions with the liberation of molecular hydrogen. This unprecedented, environmentally benign reaction is homogenously catalyzed by a dearomatized ruthenium pincer PNN complex. Copyright
- Gnanaprakasam, Boopathy,Ben-David, Yehoshoa,Milstein, David
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supporting information; experimental part
p. 3169 - 3173
(2011/02/23)
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- Improved enzyme activity and enantioselectivity in organic solvents by methyl-β-cyclodextrin
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The use of enzymes in organic solvents to introduce chirality to a number of relevant organic compounds has been well documented. However, there are still major drawbacks in such applications, in particular the frequently much lower enzyme activity under nonaqueous conditions. In addition, the reaction outcome (substrate enantioselectivity and reaction rates) cannot be accurately predicted. To overcome these limitations, herein we introduce methyl-β-cyclodextrin (MβCD) as a new macrocyclic additive to simultaneously enhance the activity and enantioselectivity of dehydrated subtilisin Carlsberg suspended in neat organic solvents. MβCD was efficient in dramatically increasing the activity and significantly improving the enantioselectivity of subtilisin in co-lyophilizates when compared to the powder lyophilized from buffer alone. The initial rate determined for the transesterification between sec-phenethyl alcohol and vinyl butyrate increased by up to 164-fold and the enantioselectivity could be doubled. In addition, marked solvent effects were noted. To investigate the possible relationship between enzyme structure and these kinetic data, the secondary structure of subtilisin was investigated by Fourier transform infrared (FTIR) spectroscopy under all relevant conditions. Using the α-helix content determined from the amide I vibrational band as the main quantitative parameter, we found that MβCD is partially efficient in ameliorating dehydration-induced structural perturbations. Suspension of the subtilisin - MβCD co-lyophilizate in the various solvents revealed solvent-induced structural perturbations in some of them (e.g., acetonitrile), while no such changes were observed in others (e.g., THF and 1,4-dioxane). For the first time the results demonstrated that enantioselectivity and structural intactness in the various solvents were clearly related. Increase in the enzyme activity in contrast is mainly caused by increased structural mobility of subtilisin in the solvents by MβCD. We conclude that it is important to carefully select the additive and the solvent system to achieve high enantioselectivity and activity in such applications. Simultaneous improvement of both enzyme properties requires careful optimization of the enzyme formulation and proper selection of a suitable solvent. FTIR spectroscopy has proven to be a very valuable methodology to structurally guide such an optimization procedure.
- Griebenow, Kai,Laureano, Yanira Diaz,Santos, Angelica M.,Clemente, Ileana Montanez,Rodriguez, Luiz,Vidal, Michael W.,Barletta, Gabriel
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p. 8157 - 8163
(2007/10/03)
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- Oxidative Transformations of Aldazines and Ketazines with Organic Peroxyacids
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Oxidation of aromatic aldazines and ketazines with various peroxycarboxylic acids was investigated.It was found that one part of azine molecule 2 was converted into carbonyl compound 1 or related acid 3 while the second part was transformed into carboxylic ester 4 related to peroxyacid used as an oxidant.It was revealed that aromatic azines could be used as a source of diazaarylmethanes and mechanisms of reactions studied were postulated. aldazines, carboxylic esters, ketazines, oxidation, peroxycarboxylic acids
- Mlochowski, J.,Giurg, M.
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p. 2333 - 2342
(2007/10/02)
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- Preparative Production of Optically Active Esters and Alcohols Using Esterase-Catalyzed Stereospecific Transesterification in Organic Media
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A novel enzymatic approach to the production of optically active alcohols and esters from racemates is developed.It involves the use of esterase catalyzed transesterifications carried out in biphasic aqueous-organic mixtures.Water-insoluble substrates constitute the organic phase, while the enzyme is located in the aqueous phase.Since the fraction of the latter phase can be made very low, such an arrangement solves the problem of both the competition of an alcohol (the nucleophile) with water in the enzymatic reaction and poor solubility of most organic esters and alcohols in water.By use of porous supports (Sepharose or Chromosorb) filled with aqueous solutions of hog liver carboxyl esterase as a stereoselective catalyst and methyl propionate as a matrix ester, the following optically active alcohols and their propionic esters were produced on a preparative scale: 3-methoxy-1-butanol, 3-methyl-1-pentanol, 3,7-dimethyl-1-octanol, and β-citronellol.To overcome a rather narrow substrate specificity of hog liver carboxyl esterase, a nonspecific lipase from yeast (Candida cylindracea) also was employed as a stereoselective transesterification catalyst.Using an aqueous solution of this enzyme confined to the pores of Chromosorb and tributyrin as a matrix ester, we have prepared gram amounts of the following optically active alcohols and their butyric esters: 2-butanol, sec-phenethyl alcohol, 2-octanol, 1-chloro-2-propanol and 2,3-dichloro-1-propanol (subsequently nonenzymatically converted to optically active propylene oxide and epichlorohydrin, respectively), 6-methyl-5-hepten-2-ol, and 1,2-butanediol.
- Cambou, Bernard,Klibanov, Alexander M.
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p. 2687 - 2692
(2007/10/02)
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