- Ligand-Free Copper-Catalyzed Ullmann-Type C?O Bond Formation in Non-Innocent Deep Eutectic Solvents under Aerobic Conditions
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An efficient and novel protocol was developed for a Cu-catalyzed Ullmann-type aryl alkyl ether synthesis by reacting various (hetero)aryl halides (Cl, Br, I) with alcohols as active components of environmentally benign choline chloride-based eutectic mixtures. Under optimized conditions, the reaction proceeded under mild conditions (80 °C) in air, in the absence of additional ligands, with a catalyst [CuI or CuII species] loading up to 5 mol% and K2CO3 as the base, providing the desired aryloxy derivatives in up to 98 % yield. The potential application of the methodology was demonstrated in the valorization of cheap, easily available, and naturally occurring polyols (e. g., glycerol) for the synthesis of some pharmacologically active aryloxypropanediols (Guaiphenesin, Mephenesin, and Chlorphenesin) on a 2 g scale in 70–96 % yield. Catalyst, base, and deep eutectic solvent could easily and successfully be recycled up to seven times with an E-factor as low as 5.76.
- Quivelli, Andrea Francesca,Marinò, Manuela,Vitale, Paola,García-álvarez, Joaquín,Perna, Filippo M.,Capriati, Vito
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- HPLC separation of 2-aryloxycarboxylic acid enantiomers on chiral stationary phases
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The possibility for separating enantiomers of a number of practically significant 2-aryloxycarboxylic acids was studied by normal- and reversed-phase HPLC on popular chiral stationary phases. The best separation parameters were achieved on the chiral phases with the polysaccharide base Chiralcel OD-H and Chiralpack AD under the normal-phase HPLC conditions. The (S)- and (R)-enantiomers of 2-(1-naphthyloxy)- and 2-(2-iodophenoxy)propionic acids with enantiomeric excess ee >99% were isolated using preparative chiral HPLC.
- Charushin, V. N.,Chulakov, E. N.,Krasnov, V. P.,Levit, G. L.,Sadretdinova, L. Sh.,Tumashov, A. A.,Vakarov, S. A.
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p. 900 - 907
(2021/06/07)
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- Mutual Kinetic Resolution of Racemic 3,4-Dihydro-3-methyl-2H-[1,4]benzoxazines with Acyl Chlorides of Racemic O-Phenyllactic Acids and DFT Modelling of Transition States
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The effect of the electronic nature of the para substituent on the aromatic ring of 2-aryloxypropionyl chlorides on the stereochemical outcome of the acylation of 3,4-dihydro-3-methyl-2H-[1,4]benzoxazine and its 7,8-difluoro-containing analogue has been studied. The geometries of the diastereoisomeric transition states and the corresponding Gibbs free enthalpies of activation were determined through DFT calculations at the COSMO-CH2Cl2-B3LYP-D3-gCP/def2-TZVP (or def2-SVP)//B3LYP-D3-gCP/def2-SVP level of theory. It has been found that a low-cost quantum chemical calculation at a chosen level of theory describes well the quantitative dependence of the selectivity of acylation on the structures of the reagents. The obtained results indicate that aromatic interactions between the reagents play a significant role in the process of stereodifferentiation, ensuring high selectivity of the acylation of benzoxazines with 2-aryloxyacyl chlorides.
- Korolyova, Marina A.,Vakarov, Sergey A.,Kozhevnikov, Dmitry N.,Gruzdev, Dmitry A.,Levit, Galina L.,Krasnov, Victor P.
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p. 4577 - 4585
(2018/09/06)
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- Resolution of (R, S)-ethyl-2-(4-hydroxyphenoxy) propanoate using lyophilized mycelium of Aspergillus oryzae WZ007
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The mycelium of Aspergillus oryzae WZ007 was successfully developed to kinetic resolution of (R, S)-ethyl-2-(4-hydroxyphenoxy) propanoate ((R, S)-EHPP) for production of (R)-ethyl-2-(4-hydroxyphenoxy) propanoate ((R)-EHPP). The key biocatalytic process parameters (pH, temperature, rotation speed and substrate concentration) were optimized. Under the optimum conditions, the optical purity of (R)-EHPP was improved up to >99% when the conversion was above 49%. A. oryzae WZ007 whole-cell lipase exhibited high reaction capacity, enantioselectivity and good reusability. The tolerable substrate concentration was 0.5 mol/L, and dry mycelium of A. oryzae WZ007 maintains over 80% of its initial activity after eight repeating cycles. Therefore the enzymatic preparation of (R)-EHPP route was suitable for industrial application.
- Zheng, Jian-Yong,Wu, Jia-Yu,Zhang, Yin-Jun,Wang, Zhao
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- A new method for production of chiral 2-aryloxypropanoic acids using effective kinetic resolution of racemic 2-aryloxycarboxylic acids
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We report a novel method for the preparation of 2-aryloxypropanoic acids by kinetic resolution of racemic 2-aryloxypropanoic acids using enantioselective esterification. The usage of pivalic anhydride (Piv2O) as an activating agent, bis(a-naphthyl)methanol ((α-Np)2CHOH) as an achiral alcohol, and (+)-benzotetramisole ((+)-BTM) as a chiral acyl-transfer catalyst enables the effective separation of various racemic 2-aryloxypropanoic acids to afford optically active carboxylic acids and the corresponding esters with high enantioselectivities. Furthermore, theoretical calculations of the transition states required to form the chiral esters successfully proved the enantiomer recognition mechanism of the asymmetric esterification.
- Tengeiji, Atsushi,Nakata, Kenya,Ono, Keisuke,Shiina, Isamu
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p. 1227 - 1252
(2013/08/23)
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- Kinetic resolution of α-substituted alkanoic acids promoted by homobenzotetramisole
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A new method for catalytic nonenzymatic kinetic resolution of α-substituted alkanoic acids has been developed, which relies on their activation with DCC followed by enantioselective alcoholysis of the intermediate symm-anhydrides in the presence of the amidine-based catalyst homobenzotetramisole (HBTM). Moderate to excellent selectivity factors (s=5-96) have been obtained in the case of several classes of substrates, namely, α-aryl-, α-aryloxy/alkoxy-, α-halo-, α-azido-, and α-phthalimido-alkanoic acids. Under similar conditions, α-(arylthio/alkylthio)-alkanoic acids undergo dynamic kinetic resolution providing corresponding esters in up to 92 % ee and up to 93 % yield. Copyright
- Yang, Xing,Birman, Vladimir B.
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supporting information; experimental part
p. 11296 - 11304
(2011/10/19)
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- Enantioselective hydrogenation of α-aryloxy and α-alkoxy α,β-unsaturated carboxylic acids catalyzed by chiral spiro iridium/phosphino-oxazoline complexes
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The iridium-catalyzed highly enantioselective hydrogenation of α-aryloxy and α-alkoxy-substituted α,β-unsaturated carboxylic acids was developed. By using chiral spiro phosphino-oxazoline ligands, the hydrogenation proceeded smoothly to produce various α-aryloxy- and α-alkoxy-substituted carboxylic acids with extremely high enantioselectivities (ee up to 99.8%) and reactivities (TON up to 10 000) under mild conditions. The hydrogenation of R-benzyloxy-substituted α,β-unsaturated acids provided an efficient alternative for the synthesis of chiral R-hydroxy acids after an easy deprotection. A mechanism involving a catalytic cycle between IrI and IrIII was proposed on the basis of the coordination model of the unsaturated acids with the iridium metal center. The rationality of the catalytic cycle, with an olefin dihydride complex as the key intermediate, was supported by the deuterium-labeling studies. The X-ray diffraction analysis of the single crystal of catalyst revealed that the rigid and sterically hindered chiral environment created by the spiro phosphino-oxazoline ligands is the essential factor that permits the catalyst to obtain excellent chiral discrimination. A chiral induction model was suggested on the basis of the catalyst structure and the product configuration.
- Li, Shen,Zhu, Shou-Fei,Xie, Jian-Hua,Song, Song,Zhang, Can-Ming,Zhou, Qi-Lin
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supporting information; experimental part
p. 1172 - 1179
(2010/04/01)
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- Homobenzotetramisole-catalyzed kinetic resolution of α-Aryl-, α-Aryloxy-, and α-Arylthioalkanoic acids
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Effective kinetic resolutions of α-aryl-, αaryloxy-, and α-arylthioalkanoic acids have been achieved via in situ generation of their symmetrical anhydrides and enantioselective alcoholysis in the presence of homobenzotetramisole (HBTM) 3.
- Yang, Xing,Birman, Vladimir B.
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supporting information; experimental part
p. 2301 - 2304
(2010/01/19)
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- A great improvement of the enantioselectivity of lipase-catalyzed hydrolysis and esterification using co-solvents as an additive
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Addition of co-solvents such as tetrahydrofuran resulted in a great improvement of the enantioselectivity of lipase-catalyzed hydrolysis of butyl 2-(4-substituted phenoxy)propanoates in an aqueous buffer solution. On the other hand, lipase lyophilized from an aqueous solution containing the co-solvents catalyzed highly enantioselective esterification of 2-(4-substituted phenoxy)propionic acids, 2-(4-isobutylphenyl)propionic acid (ibuprofen), and 2-(6-methoxy-2-naph-thyl)propionic acid (naproxen) in an organic solvent. An increase in the E value up to two orders of magnitude was observed for some substrates. The origin of the enantioselectivity enhancement caused by the co-solvent addition was mainly attributed to a significant deceleration in the initial reaction rate for the incorrectly binding enantiomer, as compared with that for the correctly binding enantiomer. From the results of FT-1R, CD, and ESR spectra, the co-solvent addition was also found to bring about a partial destruction of the tertiary structure of lipase.
- Nishigaki, Tomohiro,Yasufuku, Yoshitaka,Murakami, Sayuri,Ebara, Yasuhito,Ueji, Shin-Ichi
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experimental part
p. 617 - 622
(2009/04/11)
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- Parallel kinetic resolution of 2-methoxy and 2-phenoxy-substituted carboxylic acids using a combination of quasi-enantiomeric oxazolidinones
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2-Methoxy-2-phenyl acetic acid and 2-phenoxy-2-phenylpropionic acid were resolved by the parallel kinetic resolution of their corresponding pentafluorophenyl active ester using a quasi-enantiomeric combination of lithiated oxazolidinones.
- Boyd, Ewan,Chavda, Sameer,Eames, Jason,Yohannes, Yonas
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p. 476 - 482
(2007/10/03)
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- A method to greatly improve the enantioselectivity of lipase-catalyzed hydrolysis using sodium dodecyl sulfate (SDS) as an additive
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The addition of sodium dodecyl sulfate (SDS) resulted in a dramatic improvement of the enantioselectivity of the lipase-catalyzed hydrolysis of racemic butyl 2-(4-substituted phenoxy)propanoates, racemic butyl 2-(4-isobutylphenyl)propanoate, and racemic butyl 2-(6-methoxy-2-naphthyl) propanoate in an aqueous buffer solution. An increase in the E value by up to two orders of magnitude was observed for some esters. As to the effects of SDS on the structure of a lipase, FT-IR and fluorescence measurements suggest some conformational change and/or an increase of the flexibility of the lipase, although the native secondary structure of the lipase is held even in the presence of 100 mM SDS. The origin of the enantioselectivity enhancement brought about by the addition of SDS is briefly discussed on the basis of the values of the initial rates obtained for each enantiomer of the substrate.
- Mori, Shuichi,Yumoto, Hiromi,Matsumi, Rina,Nishigaki, Tomohiro,Ebara, Yasuhito,Ueji, Shin-Ichi
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p. 3698 - 3702
(2007/10/03)
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- Hydrogen bonding in enantiomeric versus racemic mono-carboxylic acids; a case study of 2-Phenoxy-Propionic acid
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The structural and thermodynamic backgrounds for the crystallization behaviour of racemates have been investigated using 2-phenoxypropionic acid (PPA) as an example. The racemate of PPA behaves normally and forms a racemic compound that has a higher melting point and is denser than the enantiomer. Low-temperature crystal structures of the pure enantiomer, the enantiomer cocrystallized with n-alkanes and the racemic acid showed that hydrogen-bonded dimers that form over crystallographic symmetry elements exist in all but the structure of the pure enantiomer. A database search for optically pure chiral mono-carboxylic acids revealed that the hydrogen-bonded cyclic dimer is the most prevalent hydrogen-bond motif in chiral mono-carboxylic acids. The conformation of PPA depends on the hydrogen-bond motif; the antiplanar conformation relative to the ether group is associated with a catemer hydrogen-bonding motif, whereas the more abundant synplanar conformation is found in crystals that contain cyclic dimers. Other intermolecular interactions that involve the substituent of the carboxylic group were identified in the crystals that contain the cyclic dimer. This result shows how important the nature of the substituent is for the crystal packing. The differences in crystal packing have been related to differences in melting enthalpy and entropy between the racemic and enantiomeric acids. In a comparison with the equivalent 2-(4-chlorophenoxy)-propionic acids, the differences between the crystal structures of the chloro and the unsubstituted acid have been identified and related to thermodynamic data.
- Sorensen, Henning Osholm,Larsen, Sine
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p. 132 - 140
(2007/10/03)
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- Flexibility of lipase brought about by solvent effects controls its enantioselectivity in organic media
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The behavior of the enantioselectivity of Candida rugosa lipase was studied in the esterification of 2-(4-substituted phenoxy)propionic acids with 1-butanol in aliphatic, aromatic, and ethereal solvents, (cyclohexane, heptane, toluene, benzene, isooctane, dibutylether, etc.). Changing the solvent from cyclohexane to tert-butyl methyl ether, the isotropic signal increased quickly and the spectral line narrowed in width. The enzyme enantioselectivity in organic solvents was mainly controlled by its flexibility. The enantioselectivity of lipase in organic solvents was closely correlated with the lipase flexibility brought about by the cooperative solvent effects rather than with a sole solvent property, e.g., dielectric constant and hydrophobicity.
- Ueji, Shin-ichi,Taniguchi, Tomohiko,Okamoto, Takashi,Watanabe, Keiichi,Ebara, Yasuhito,Ohta, Hitoshi
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p. 399 - 403
(2007/10/03)
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- Absolute stereochemical determination of chiral carboxylic acids
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(matrix presented) Monoamidation of 1,4-diaminobenzene with α-chiral carboxylic acids leads to a carrier strategy for absolute stereochemical determination with bis-zinc porphyrin tweezers by exciton-coupled circular dichroism (ECCD). The helicity induced in the porphyrin tweezers upon complexation with the derivatized carrier originates from the preferred conformation of the Ccarbonyl-Cchiral bond. Correct ECCD signs can be predicted by the rotamer that places the large group perpendicular to the carbonyl group with the small group facing the porphyrin.
- Yang, Qifei,Olmsted, Courtney,Borhan, Babak
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p. 3423 - 3426
(2007/10/03)
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- Dimethyl sulfoxide as a co-solvent dramatically enhances the enantioselectivity in lipase-catalysed resolutions of 2-phenoxypropionic acyl derivatives
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We recently reported that the enantioselectivity for subtilisin-catalysed hydrolysis of ethyl 2-(4-substituted phenoxy)-propionates in aqueous buffer is found to be dramatically enhanced by addition of dimethyl sulfoxide (DMSO). In our present work, as one of the useful methods for improving the enzyme's enantioselectivity, this approach using DMSO is tested for both hydrolysis and transesterification catalysed by various lipases. For instance, for Candida rugosa lipase-catalysed hydrolysis in aqueous buffer containing DMSO, the optimum additive conditions (50-65 vol% DMSO) markedly enhance the enantioselectivity toward the substrates used, as compared with that for no-additive conditions, in spite of a decrease in the enzymatic activity. On the other hand, for Pseudomonas cepacia lipase-catalysed hydrolysis, the addition of DMSO to the reaction medium enhances the enantioselectivity with an increase in the enzymatic activity. Also, the DMSO effect on the enantioselectivity can apply to the lipase-catalysed transesterification in organic solvent. A mechanism for the DMSO-induced enhancement of the lipase's enantioselectivity is briefly discussed on the basis of the values of the initial rates obtained for each enantiomer of the substrate used.
- Watanabe, Keiichi,Ueji, Shin-Ichi
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p. 1386 - 1390
(2007/10/03)
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- Resolution of (±)-mandelic- and (±)-2-(chiorophenoxy)propionic-acid derivatives by crystallization of their diastereomeric amides with (R)- or (S)-α-arylethylamines
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An alternative and cost effective route for the resolution in high ees (95-99%) of (±)-mandelic-and (±)-2-(chlorophenoxy)propionic- acid derivatives is reported. The key step involves the covalent derivatization and separation of their diastereomeric amides with (R)- or (S)-α- arylethylamines.
- Jourdain, Franck,Hirokawa, Takahiko,Kogane, Tamizo
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p. 2509 - 2512
(2007/10/03)
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- Resolution of (±)-mandelic- and (±)-2-(chlorophenoxy)propionic-acid derivatives by crystallization of their diastereomeric amides with (R)- or (S)-α-arylethylamines
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An alternative and cost effective route for the resolution in high ees (95-99%) of (±)-mandelic-and (±)-2-(chlorophenoxy)propionic- acid derivatives is reported. The key step involves the covalent derivatization and separation of their diastereomeric amides with (R)- or (S)-α- arylethylamines.
- Jourdain, Franck,Hirokawa, Takahiko,Kogane, Tamizo
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p. 2307 - 2310
(2007/10/03)
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- Flash Chiral Chromatography using Carbohydrate Carbamate-coated Silica
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Enantiomers of many chiral compounds are resolved rapidly on a preparative scale by passage through a column packed with flash chromatography silica which has been physically coated with a carbohydrate carbamate.
- Matlin, Stephen A.,Grieb, Sally J.,Belenguer, Ana M.
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p. 301 - 302
(2007/10/02)
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- Double Enantioselective Transesterification of Racemic Carboxylic Esters and Cycil meso-Diols by Lipase Catalysis
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Lipase-catalysed double enantioselective transesterifications of racemic carboxylic esters and cyclic meso-diols to give the hydroxy esters 3, 6, 9, 11 and 14 have been investigated.The selectivity of this process is determined by the structure of both substrates and the origin of the lipase.In four of the five cases investigated, lipase SP 382 shows the highest activity and selectivity.In the products, excepting the acyl part of compounds 3, (S)-selectivity for both the alcohol and the acyl mojety has been observed.However, regarding the acyl part the selectivity is poor compared with that of the alcohol part.Application of this method allows us to prepare enantiomerically pure compounds with at least three asymmetric centres in one biocatalytic step if the reaction partners are matching and/or the products are easy to separate as found for compounds 9a, 9c and 11a for instance. the X-ray molecular strucutres of compounds 9a and 11a are reported.
- Theil, Fritz,Kunath, Annamarie,Ramm, Matthias,Reiher, Thomas,Schick, Hans
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p. 1509 - 1516
(2007/10/02)
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- Enzymatic enantioselective ester hydrolysis by carboxylesterase NP
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The enzymatic hydrolysis of a series of carboxylic esters by carboxylesterase NP has been investigated in order to determine the scope and limitations of this enzyme. 2-Substituted propionates were hydrolyzed with high enantioselectivity when an aromatic moiety was part of the 2-substituent.Enantioselective hydrolysis could be accomplished with several 2-arypropionates, 2-(aryloxy)propionates and N-arylalanine esters.The propionate esters yielded propionic acids as (S) enantiomers, whereas the alanine esters yielded the (R) enantiomers.Without a 2-aryl substituent, the enzymatic hydrolysis of the propionates occurred at a lower rate without acceptable enantioselectivity.In addition to 2-substituted propionates, only a few other esters were hydrolyzed with high enantioselectivity by carboxylesterase NP, such as some prochiral disubstituted malonates. 1-Phenylethylacetate was the only substrate with chirality in the alcohol part of the ester that was found to be hydrolyzed enantioselectively.Carboxylesterase NP proved to be a powerful enzyme for kinetic resolution of propionate esters with an aromatic ring containing a 2-substituent.
- Smeets, J. W. H.,Kieboom, A. P. G.
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p. 490 - 495
(2007/10/02)
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- Enantioselective Hydrolysis of Aryloxypropionic Esters by Bovine Serum Albumin: Enhancement in Selectivity by β-Cyclodextrin
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Bovine serum albumin catalyzed hydrolysis of racemic aryloxypropionic esters affords appreciable enantioselectivity.The effect of β-cyclodextrin this process of hydrolysis has been studied.
- Kamal, Ahmed,Ramalingam, T.,Venugopal, N.
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- Direct Optical Resolution of Carboxylic Acids by Chyral HPLC on Tris(3,5-dimethylphenylcarbamate)s of Cellulose and Amylose
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A variety of racemic carboxylic acids have been for the first time directly resolved by normal-phase, high-performance liquid chromatography using a hexane-2-propanol eluting system containing a small amount (ca. 1percent) of a strong carboxylic acid, like formic acid, trichloroacetic acid, and trifluoroacetic acid.
- Okamoto, Yoshio,Aburatani, Ryo,Kaida, Yuriko,Hatada, Koichi
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p. 1125 - 1128
(2007/10/02)
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- Enzyme catalysed hydrolysis of chlorophenoxypropionates
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We report on the enzymatic hydrolysis of methyl 2-phenoxypropionate and of the following chlorinated derivatives: methyl o-chloro-, m-chloro-, p-chloro-, and o,p-dichloro-2-phenoxypropionates. α-Chymotripsyn, lipase, and pig liver esterase have an R enantioselectivity whereas subtilisin has an S enantioselectivity.Enantiomeric excess (e.e.) cover a wide range (from 5 to 100percent).
- Chenevert, Robert,D'Astous, Linda
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p. 1219 - 1222
(2007/10/02)
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- Preparation of optically active carboxylic acids
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Optically active carboxylic acids STR1 where R1 is an organic radical which is linked to the asymmetric C' atom via a carbon atom and R2 is one of the radicals R1 (but not the same radical), halogen or an organic radical which is bonded to the asymmetric C' atom via an oxygen atom, are prepared by reacting a ketene II STR2 with an alcohol in a homogeneous liquid phase in the presence of a tertiary amine III and then converting the resulting ester into the acid, using an optically active alcohol IV.
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- Preparation of Optical Active 2-(Aryloxy)propionic Acids by Kinetic Resolution. - Herbizides
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2-(Aryloxy)propionic anhydrides 2 were transformed with 70-90percent stereoselectivity into the R,S- or S,R-diastereomeric esters 4, respectively, on reaction with stoichiometric amounts of optical active 1-(4-pyridyl)ethanol (3).The acid 1 set free in one mol equivalent during this reaction was mainly the other enantiomer in 62-72percent optical yields.By treatment with boiling acetic anhydride and pyridine the acid 1 is transformed back into racemic anhydride 2.The ester 4 was hydrolyzed with aqueous acid to optical active 1 with regeneration of the optical active alcohol 3.In this way a quantitative transformation of racemic acids 1 into that enantiomer which is an active herbizide is possible using 3 as optical active auxiliary material.
- Salz, Ulrich,Ruechardt, Christoph
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p. 3457 - 3462
(2007/10/02)
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