- Enantioseparation of Mandelic Acid Enantiomers with Magnetic Nano-Sorbent Modified by a Chiral Selector
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In this study, R(+)-α-methylbenzylamine-modified magnetic chiral sorbent was synthesized and assessed as a new enantioselective solid phase sorbent for separation of mandelic acid enantiomers from aqueous solutions. The chemical structures and magnetic pr
- Tarhan, Tuba,Tural, Bilsen,Tural, Servet,Topal, Giray
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- Process Development for the Production of (R)-(-)-Mandelic Acid by Recombinant Escherichia coli Cells Harboring Nitrilase from Burkholderia cenocepacia J2315
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(R)-(-)-Mandelic acid is an important chiral building block that is widely used in pharmacy and the production of fine chemicals. A more advanced method for obtaining (R)-(-)-mandelic acid is direct hydrolysis of the corresponding racemic mandelonitrile. In order to develop a cost-effective process, a highly efficient enantioselective nitrilase BCJ2315 from Burkholderia cenocepacia J2315 was used for the biotransformation of mandelonitrile to (R)-(-)-mandelic acid. The recombinant Escherichia coli M15/BCJ2315 showed high substrate tolerance and could completely hydrolyze up to 250 mM of mandelonitrile. A fed-batch reaction was performed by periodically or continuously dosing the substrate into the reactor to alleviate substrate inhibition in a monophasic buffer system. Finally, the highest substrate loading (2.9 M) was achieved in the continuous fed batch reaction mode, giving (R)-(-)-mandelic acid at the highest concentration (2.3 M, 350 g/L) with 97.4% ee ever reported. The hydrolysis process was easily scaled up to 2 and 10 L, indicating the potential for the industrial production of optically pure (R)-(-)-mandelic acid.
- Wang, Hualei,Fan, Haiyang,Sun, Huihui,Zhao, Li,Wei, Dongzhi
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- An organic solvent and thermally stable lipase from Burkholderia ambifaria YCJ01: Purification, characteristics and application for chiral resolution of mandelic acid
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A solvent-tolerant bacterium Burkholderia ambifaria YCJ01 was newly isolated by DMSO enrichment of the medium. The lipase from the strain YCJ01 was purified to homogeneity with apparent molecular mass of 34 kDa determined by SDS-PAGE. The purified lipase exhibited maximal activity at a temperature of 60 °C and a pH of 7.5. The lipase was very stable below 55 °C for 7 days (remaining 80.3% initial activity) or at 30 °C for 60 days. PMSF significantly inhibited the lipase activity, while EDTA had no effect on the activity. Strikingly, the lipase showed distinct super-stability to the most tested hydrophilic and hydrophobic solvents (25%, v/v) for 60 days, and different optimal pH in contrast with the alkaline lipase from B. cepacia S31. The lipase demonstrated excellent enantioselective transesterification toward the S-isomer of mandelic acid with a theoretical conversion yield of 50%, eep of 99.9% and ees of 99.9%, which made it an exploitable biocatalyst for organic synthesis and pharmaceutical industries.
- Yao, Changjin,Cao, Yan,Wu, Shanshan,Li, Shuang,He, Bingfang
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- Highly efficient resolution of mandelic acid using lipase from Pseudomonas stutzeri LC2-8 and a molecular modeling approach to rationalize its enantioselectivity
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Mandelic acid, a key precursor of chiral synthons, was successfully acylated in diisopropyl ether. The reaction was catalyzed by the lipase from Pseudomonas stutzeri LC2-8, and vinyl acetate was employed as acyl donor. Under the optimized reaction conditions, a resolution of 180 mM (55 g/L) mandelic acid was achieved. (S)-O-Acetyl mandelic acid was enantioselectivity formed in >99% ee at a yield close to the maximum theoretical value for kinetic resolution (50%). The highly substrate tolerable and enantioselective nature of lipase LC2-8 suggests that it is of great potential for the practical resolution of racemic mandelic acid. Additionally, the high enantiopreference of lipase LC2-8 toward (S)-mandelic acid in acetylation was also rationalized through molecular docking and molecular dynamics simulations.
- Cao, Yan,Wu, Shanshan,Li, Jiahuang,Wu, Bin,He, Bingfang
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- R-mandelic acid production with immobilized recombinant Escherichia coli cells in a recirculating packed bed reactor
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A recirculating packed bed reactor (RPBR) was used for efficient production of R-mandelic acid (R-MA) by kinetic resolution of racemic R,S-mandelonitrile (R,S-MN) using the recombinant E. coli cells crosslinked with diatomite (DA)/glutaraldehyde (GA)/polyethyleneimine (PEI). The performance and productivity of RPBR were evaluated by several parameters, including cell load, substrate feeding rate, height diameter (H/D) ratio, reactor structures, and operation stability. The kinetic resolution process showed higher initial reaction rate (1.52 mM/min) and yield (100%) by recycling 100 mL of substrate solution (70 mM) through RPBR packed with 6.0 g immobilized cells at a substrate-feeding rate of 19 mL/min while the H/D ratio was 2.8. The immobilized cells were successfully applied into kinetic resolution of R,S-MN in the RPBR for 50 batches with an average productivity of 4.12 g/L/h for R-MA with >99% of enantiomeric excess.
- Zhang, Xin-Hong,Liu, Zhi-Qiang,Xue, Ya-Ping,Yang, Bo,Xu, Ming,Zheng, Yu-Guo
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- Optical Resolution of Phenylalanine and Mandelic Acid
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The optical resolutions of phenylalanine and mandelic acid were performed by complex formation with Cu2+, D- and L-mandelic acids were completely resolved by forming a complex with L-phenylalanine, while the maximum optical purity of D- and L-p
- Yamamoto, Yasushi,Kato, Shinji,Yamashita, Hiroshi,Maekawa, Takashi
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- Screening for enantioselective nitrilases: Kinetic resolution of racemic mandelonitrile to (R)-(-)-mandelic acid by new bacterial isolates
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Several new microorganisms have been isolated with high nitrilase activity against (RS)-mandelonitrile using the enrichment culture technique. The organisms were cultivated in liquid culture and the enzyme activity was determined at different phases of growth. The organisms having high enzyme titre were further grown and used as catalysts for the transformation of mandelonitrile to mandelic acid. The percentage conversion was checked with RP-HPLC and the enantiomeric excess was determined on a chiral column. Three isolates gave the desired product, (R)-(-)-mandelic acid with high ee (%) and were identified as Pseudomonas putida, Microbacterium paraoxydans and Microbacterium liquefaciens. All three isolates showed good specific activity (0.33-0.50U/mgmin) with high ee (>93%) and E values. The conversion of racemic mandelonitrile to mandelic acid by these isolates was compared: P. putida was found to be the most suitable biocatalyst for further studies as it showed higher reaction rate (kRxn), lower Km, better growth rate (μ), good yield and ee values and higher stability compared to the other two microorganisms.
- Kaul, Praveen,Banerjee, Anirban,Mayilraj,Banerjee, Uttam C.
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- Surface functionalization of chitosan-coated magnetic nanoparticles for covalent immobilization of yeast alcohol dehydrogenase from Saccharomyces cerevisiae
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A novel and efficient immobilization of yeast alcohol dehydrogenase (YADH, EC1.1.1.1) from Saccharomyces cerevisiae has been developed by using the surface functionalization of chitosan-coated magnetic nanoparticles (Fe 3O4/KCTS) as support. The magnetic Fe3O 4/KCTS nanoparticles were prepared by binding chitosan alpha-ketoglutaric acid (KCTS) onto the surface of magnetic Fe3O 4 nanoparticles. Later, covalent immobilization of YADH was attempted onto the Fe3O4/KCTS nanoparticles. The effect of various preparation conditions on the immobilized YADH process such as immobilization time, enzyme concentration and pH was investigated. The influence of pH and temperature on the activity of the free and immobilized YADH using phenylglyoxylic acid as substrate has also been studied. The optimum reaction temperature and pH value for the enzymatic conversion catalyzed by the immobilized YADH were 30 °C and 7.4, respectively. Compared to the free enzyme, the immobilized YADH retained 65% of its original activity and exhibited significant thermal stability and good durability.
- Li, Gui-Yin,Zhou, Zhi-De,Li, Yuan-Jian,Huang, Ke-Long,Zhong, Ming
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- Nucleation and growth kinetics of (R)-mandelic acid from aqueous solution in the presence of the opposite enantiomer
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Resolution of mandelic acid (MA), a racemic compound, is presented in this article using direct crystallization from enantiomeric enriched water solutions. Final crystals with enantiomeric excess (ee) of (R)-MA higher than 96.4% were obtained. Because of
- Zhang, Yan,Mao, Shimin,Ray, Ajay K.,Rohani, Sohrab
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- Constituents of Prunus zippeliana leaves and branches
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The following substances were identified in the fresh leaves and branches of Prunus zippeliana MIQ.: 22-dehydroclerosteryl acetate, stigmasteryl acetate, β-sitosterol, stigmasterol, clerosterol, 22-dehydroclerosterol, β- sitosterol and stigmasterol 3-O-β-D-glucopyranoside, ursolic acid, oleanolic acid, 2α-hydroxyursolic acid, tormentic acid, methyl linolate, phytol, prunasin, dl-mandelic acid, kaempferol 3-O-[O-α-L-rhamnopyranosyl-(1 → 6)- β-D-glucopyranoside] and d-mandelic acid β-D-glucopyranoside. Worthy of note is that 24α-ethylsterols (β-sitosterol and stigmasterol) and 24β- ethylsterols (clerosterol and 22-dehydroclerosterol) were obtained together from the leaves of a higher plant.
- Kitajima,Tanaka
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- Improvement of alcaligenes faecalis nitrilase by gene site saturation mutagenesis and its application in stereospecific biosynthesis of (R)-(-)-mandelic acid
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Nitrilases have recently received considerable attention as the biocatalysts for stereospecific production of carboxylic acids. To improve the activity, the nitrilase from Alcaligenes faecalis was selected for further modification by the gene site saturation mutagenesis method (GSSM), based on homology modeling and previous reports about mutations. After mutagenesis, the positive mutants were selected using a convenient two-step high-throughput screening method based on product formation and pH indicator combined with the HPLC method. After three rounds of GSSM, Mut3 (Gln196Ser/Ala284Ile) with the highest activity and ability of tolerance to the substrate was selected. As compared to the wild-type A. faecalis nitrilase, Mut3 showed 154% higher specific activity. Mut3 could retain 91.6% of its residual activity after incubation at pH 6.5 for 6 h. In a fed-batch reaction with 800 mM mandelonitrile as the substrate, the cumulative production of (R)-(-)-mandelic acid after 7.5 h of conversion reached 693 mM with an enantiomeric excess of 99%, and the space-time productivity of Mut3 was 21.50-fold higher than that of wild-type nitrilase. The Km, Vmax, and kcat of wild-type and Mut3 for mandelonitrile were 20.64 mM, 33.74 μmol mg-1 min-1, 24.45 s-1, and 9.24 mM, 47.68 μmol mg -1 min-1, and 34.55 s-1, respectively. A homology modeling and molecular docking study showed that the diameter of the catalytic tunnel of Mut3 became longer and that the tunnel volume was smaller. These structural changes are proposed to improve the hydrolytic activity and pH stability of Mut3. Mut3 has the potential for industrial applications in the upscale production of (R)-(-)-mandelic acid.
- Liu, Zhi-Qiang,Zhang, Xin-Hong,Xue, Ya-Ping,Xu, Ming,Zheng, Yu-Guo
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- Gene cloning, expression, and characterization of a nitrilase from Alcaligenes faecalis ZJUTB10
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Nitrilases are important industrial enzymes that convert nitriles directly into the corresponding carboxylic acids. In the current work, the fragment with a length of 1068 bp that encodes the A. faecalis ZJUTB10 nitrilase was obtained. Moreover, a catalytic triad was proposed and verified by site-directed mutagenesis, and the detailed mechanism of this nitrilase was clarified. The substrate specificity study demonstrated that the A. faecalis ZJUTB10 nitrilase belongs to the family of arylacetonitrilases. The optimum pH and temperature for the purified nitrilase was 7-8 and 40 °C, respectively. Mg2+ stimulated hydrolytic activity, whereas Cu2+, Co2+, Ni2+, Ag+, and Hg2+ showed a strong inhibitory effect. The Km and vmax for mandelonitrile were 4.74 mM and 15.85 μmol min-1 mg-1 protein, respectively. After 30 min reaction using the nitrilase, mandelonitrile at the concentration of 20 mM was completely hydrolyzed and the enantiomeric excess against (R)-(-)-mandelic acid was >99%. Characteristics investigation indicates that this nitrilase is promising in catalysis applications.
- Liu, Zhi-Qiang,Dong, Li-Zhu,Cheng, Feng,Xue, Ya-Ping,Wang, Yuan-Shan,Ding, Jie-Nv,Zheng, Yu-Guo,Shen, Yin-Chu
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- Designing of amino functionalized imprinted polymeric resin for enantio-separation of (±)-mandelic acid racemate
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S-Mandelic acid (MA) enantio-selective resinous material functionalized with –NH2 groups has been developed and effectively utilized in chiral separation of (±)-MA racemate solution. S-MA has first combined with the polymerizable p-aminophenol and form the corresponding amide derivative, which was then polymerized with phenol/formalin using HCl as a catalyst. The stereo-selective –NH2 functionalized binding sites were then generated within the resin upon the alkaline degradation of the amide linkages followed by acidic treatments that will expel the resin incorporated S-MA out of the polymeric material to get the S-MA imprinted polymer (S-MAPR). The synthesized S-MA chiral amide derivative along with the developed polymeric resin was investigated by various techniques including FTIR and NMR spectra that confirmed the executed chemical modifications. In addition, the morphological appearance of the obtained resins were observed using SEM images. Moreover, the S-MAPR resin was examined to optimize the enantio-selective separation conditions and the studies indicated that the adsorption reached the highest value at pH 7 and the maximum capacity was 243 ± 1 mg/g. In addition, the chiral separation of (±)-MA racemic solution was successfully executed by the S-MAPR separation column with 55% and 82% enantiomeric excess of R- and S-MA within both the initial loading and recovery eluant solutions, respectively.
- Alhawiti, Aliyah S.,Monier,Elsayed, Nadia H.
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- High-yield DL-mandelic acid synthesis process
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The invention provides a high-yield DL-mandelic acid synthesis process. The synthesis process specifically comprises the following steps: 1, treating benzaldehyde by using sodium hydrogen sulfite to obtain benzaldehyde sodium hydrogen sulfite; 2, extracting the benzaldehyde sodium hydrogen sulfite by using an organic solvent, recovering unreacted benzaldehyde in the benzaldehyde sodium hydrogen sulfite, and adding sodium cyanide after the extraction is completed to prepare mandelonitrile; 3, adding an inorganic acid, and then carrying out heating and pressure maintaining treatment to hydrolyze the mandelonitrile so as to obtain mandelic acid; and 4, purifying the mandelic acid. According to the method, the step of extracting the p-benzaldehyde sodium hydrogen sulfite salt is added, so that the probability that the product purity is reduced due to benzoin condensation is reduced, the recycled benzaldehyde can be returned to the raw material for use, and the yield can be increased in multiple rounds of reactions; and the hydrolysis process of the mandelonitrile adopts heating and pressure maintaining treatment, so that consumption of inorganic acid can be reduced, and the hydrolysis efficiency is improved.
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- Method for synthesizing mandelic acid
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The invention relates to the technical field of compound preparation, and provides a method for synthesizing mandelic acid, which comprises the following steps: by using styrene as a basic raw material, trichloroisocyanuric acid as a chlorinating agent an
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Paragraph 0032; 0034-0035; 0037-0038; 0040-0041; 0043
(2021/02/06)
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- Synthesis of α-hydroxycarboxylic acids from various aldehydes and ketones by direct electrocarboxylation: A facile, efficient and atom economy protocol
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In present work, the formation of α-hydroxycarboxylic acids have been described from various aromatic aldehydes and ketones via direct electrocarboxylation method with 80-92% of yield without any side product and can be purified by simple recrystallization using sacrificial Mg anode and Pt cathode in an undivided cell, CO2at (1 atm) was continuously bubbled in the cell throughout the reaction using tetrapropylammonium chloride as a supporting electrolyte in acetonitrile. The synthesized compounds obtained in fair to excellent yield with a high level of purity. The characterization of electrocarboxylated compounds was done with spectroscopic techniques like IR, NMR (1H & 13C), mass and elemental analysis.
- Singh, Kishanpal,Sohal, Harvinder Singh,Singh, Baljit
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p. 839 - 845
(2021/04/09)
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- Enantioseparation of mandelic acid and substituted derivatives by high-performance liquid chromatography with hydroxypropyl-β-cyclodextrin as chiral mobile additive and evaluation of inclusion complexes by molecular dynamics
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The enantioseparation and resolution mechanism of mandelic acid (MA), 4-methoxymandelic acid (MMA), and 4-propoxymandelic acid (PMA) were investigated by reversed-phase high-performance liquid chromatography (HPLC) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) as a chiral mobile-phase additive and molecular dynamics simulation. The suitable chromatographic conditions for the enantioseparation of MA, MMA, and PMA were obtained. Under the selected chromatographic conditions, these enantiomers could achieve baseline separation. The results of thermodynamic parameter analysis revealed that the main driven forces for the enantioseparation of MA, MMA, and PMA could be van der Waals forces and hydrogen-bonding interactions and the chromatographic retention of these chiral compounds was an enthalpy-driven process. The results of the molecular simulation revealed that their chiral resolution mechanism on HP-β-CD was responsible for the formation of inclusion complexes of enantiomers with HP-β-CD with different conformations and binding energies. And the binding energy of HP-β-CD with (S)-isomer was larger than that with (R)-isomer, which is consistent with the experimental results of the first elution of (S)-isomer. Additionally, it is also confirmed that the interaction energies included the van der Waals energy (?Evdw), electrostatic energy (?Eelec), polar solvation energy, and SASA energy (?Esasa), and the separation factor (α) was closely connected with the disparity in the binding energies of optical isomers and HP-β-CD complexes. Meanwhile, from molecular dynamics simulation, it can be found that the ?(?Ebinding), (?(?Ebinding) = ?Ebinding,R ? ?Ebinding,S) value was in order of MA–HP-β-CD complex > MMA–HP-β-CD complex > PMA–HP-β-CD complex, which was consistent with the order of Δ(ΔG) values obtained from van't Hoff plot. This indicated that the molecular dynamics simulation has predictive function for chiral resolution.
- Shi, Jie-Hua,Lin, Zhen-Yi,Kou, Song-Bo,Wang, Bao-Li,Jiang, Shao-Liang
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supporting information
p. 675 - 684
(2021/08/16)
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- Expanding the repertoire of nitrilases with broad substrate specificity and high substrate tolerance for biocatalytic applications
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Enzymatic conversion of nitriles to carboxylic acids by nitrilases has gained significance in the green synthesis of several pharmaceutical precursors and fine chemicals. Although nitrilases from several sources have been characterized, there exists a scope for identifying broad spectrum nitrilases exhibiting higher substrate tolerance and better thermostability to develop industrially relevant biocatalytic processes. Through genome mining, we have identified nine novel nitrilase sequences from bacteria and evaluated their activity on a broad spectrum of 23 industrially relevant nitrile substrates. Nitrilases from Zobellia galactanivorans, Achromobacter insolitus and Cupriavidus necator were highly active on varying classes of nitriles and applied as whole cell biocatalysts in lab scale processes. Z. galactanivorans nitrilase could convert 4-cyanopyridine to achieve yields of 1.79 M isonicotinic acid within 3 h via fed-batch substrate addition. The nitrilase from A. insolitus could hydrolyze 630 mM iminodiacetonitrile at a fast rate, effecting 86 % conversion to iminodiacetic acid within 1 h. The arylaliphatic nitrilase from C. necator catalysed enantioselective hydrolysis of 740 mM mandelonitrile to (R)-mandelic acid in 4 h. Significantly high product yields suggest that these enzymes would be promising additions to the suite of nitrilases for upscale biocatalytic application.
- Rayavarapu, Pratima,Shah, Shikha,Sunder, Avinash Vellore,Wangikar, Pramod P.
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p. 289 - 296
(2020/05/18)
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- Direct enantioseparation of mandelic acid by high-performance liquid chromatography using a phenyl column precoated with a small amount of cyclodextrin additive in a mobile phase
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Direct enantioseparation of mandelic acid by high-performance liquid chromatography (HPLC) with a reversed phase column and a mobile phase containing a small amount of hydroxylpropyl-β-cyclodextrin (HP-β-CD) was studied as an efficient method for saving consumption of the CD additive. As a result, it was proposed that racemic mandelic acid can be analyzed with a phenyl column by using a mobile phase composed of 10 mM ammonium acetate buffer (pH 4.2) and 0.02% (w/v) HP-β-CD at a flow rate of 1.0 mL/min at 40°C after the passage of 10 mM ammonium acetate buffer (pH 4.2) containing 0.1% (w/v) HP-β-CD as a precoating mobile phase for 60 min. It is suggested that HP-β-CD is bound with a phenyl group on the surface of the stationary phase to allow a phenyl column to act as a transient chiral column, and injected mandelic acid can form the ternary complex with the adsorbed HP-β-CD. The longer retention time of D-mandelic acid than the L-isomer for HPLC can be explained from the higher stability of the HP-β-CD complex with D-mandelic acid, which was confirmed by CE experiment with HP-β-CD as a selector. The efficiency of a phenyl column compared with other stationary phases was also discussed.
- Watanabe, Yuri,Mikami, Ikko,Yamamoto, Atsushi,Aizawa, Sen-ichi,Taga, Atsushi,Mochizuki, Naoki,Ishihara, Yoshimi,Kodama, Shuji
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p. 1020 - 1029
(2020/05/04)
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- Enantioseparation of mandelic acid on vancomycin column: Experimental and docking study
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So far, no detailed view has been expressed regarding the interactions between vancomycin and racemic compounds including mandelic acid. In the current study, a chiral stationary phase was prepared by using 3-aminopropyltriethoxysilane and succinic anhydride to graft carboxylated silica microspheres and subsequently by activating the carboxylic acid group for vancomycin immobilization. Characterization by elemental analysis, Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance, and thermogravimetric analysis demonstrated effective functionalization of the silica surface. R and S enantiomers of mandelic acid were separated by the synthetic vancomycin column. Finally, the interaction between vancomycin and R/S mandelic acid enantiomers was simulated by Auto-dock Vina. The binding energies of interactions between R and S enantiomers and vancomycin chiral stationary phase were different. In the most probable interaction, the difference in mandelic acid binding energy was approximately 0.2 kcal/mol. In addition, circular dichroism spectra of vancomycin interacting with R and S enantiomers showed different patterns. Therefore, R and S mandelic acid enantiomers may occupy various binding pockets and interact with different vancomycin functions. These observations emphasized the different retention of R and S mandelic acid enantiomers in vancomycin chiral column.
- Shahnani, Mostafa,Sefidbakht, Yahya,Maghari, Shokoofeh,Mehdi, Ahmad,Rezadoost, Hassan,Ghassempour, Alireza
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supporting information
p. 1289 - 1298
(2020/08/19)
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- Semirational Design of Fluoroacetate Dehalogenase RPA1163 for Kinetic Resolution of α-Fluorocarboxylic Acids on a Gram Scale
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Here the synthetic utility of fluoroacetate dehalogenase RPA1163 is explored for the production of enantiomerically pure (R)-α-fluorocarboxylic acids and (R)-α-hydroxylcarboxylic acids via kinetic resolution of racemic α-fluorocarboxylic acids. While wild-type (WT) RPA1163 shows high thermostability and fairly wide substrate scope, many interesting yet poorly or moderately accepted substrates exist. In order to solve this problem and to develop upscaled production, in silico calculations and semirational mutagenesis were employed. Residue W185 was engineered to alanine, serine, threonine, or asparagine. The two best mutants, W185N and W185T, showed significantly improved performance in the reactions of these substrates, while in silico calculations shed light on the origin of these improvements. Finally, 10 α-fluorocarboxylic acids and 10 α-hydroxycarboxylic acids were prepared on a gram scale via kinetic resolution enabled by WT, W185T, or W185N. This work expands the biocatalytic toolbox and allows a deep insight into the fluoroacetate dehalogenase catalyzed C-F cleavage mechanism.
- Chen, Bo,Li, Min,Li, Yanwei,Ma, Ming,Tian, Shaixiao,Tong, Wei,Wang, Jian-Bo,Xu, Guangyu,Yue, Yue,Zhang, Hongxia
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p. 3143 - 3151
(2020/03/23)
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- An Enantioconvergent Benzylic Hydroxylation Using a Chiral Aryl Iodide in a Dual Activation Mode
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The application of a triazole-substituted chiral iodoarene in a direct enantioselective hydroxylation of alkyl arenes is reported. This method allows the rapid synthesis of chiral benzyl alcohols in high yields and stereocontrol, despite its nontemplated nature. In a cascade activation consisting of an initial irradiation-induced radical C-H-bromination and a consecutive enantioconvergent hydroxylation, the iodoarene catalyst has a dual role. It initiates the radical bromination in its oxidized state through an in-situ-formed bromoiodane and in the second, Cu-catalyzed step, it acts as a chiral ligand. This work demonstrates the ability of a chiral aryl iodide catalyst acting both as an oxidant and as a chiral ligand in a highly enantioselective C-H-activating transformation. Furthermore, this concept presents an enantioconvergent hydroxylation with high selectivity using a synthetic catalyst.
- Abazid, Ayham H.,Clamor, Nils,Nachtsheim, Boris J.
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p. 8042 - 8048
(2020/09/21)
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- Preparation of α-hydroxyphenylacetic acid with cyclodextrins as an effective phase-transfer catalyst and its reaction mechanism
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An effective procedure for the synthesis of α-hydroxyphenylacetic acid with cyclodextrin (CD) catalysts was developed. The phase-transfer catalyst types, catalyst loadings, reaction times, reaction temperatures, and substrate molar ratios were investigated to optimize the reaction conditions. In addition, the factors that affect the reaction were studied, and the relationship between benzaldehyde and β-cyclodextrin (β-CD) was analyzed through 2D-ROESY. The equilibrium constant when β-CD was used as the catalyst was calculated. The results indicated that β-CD is the optimal catalyst for the reported reaction (yield: 69.08%). Furthermore, the mechanism underlying the reported reaction was proposed.
- Tian, Bing Ren,Zhang, Rui Xia,Chu, Hui Min,Huang, Qing,Wang, Zhi Zhong
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p. 359 - 368
(2019/05/16)
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- Thiamine Diphosphate Dependent KdcA-Catalysed Formyl Elongation of Aldehydes
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The formose reaction, one of the oldest name reactions in organic chemistry, uses formaldehyde as a C1 unit resulting in different monosaccharides and sugar-like compounds. Nucleophilic formyl elongation is an attractive option to obtain 1,2-fu
- Germer, Philipp,Gauchenova, Ekaterina,Walter, Lydia,Müller, Michael
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p. 4276 - 4280
(2019/08/02)
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- Three-Component Synthesis of Isoquinoline Derivatives by a Relay Catalysis with a Single Rhodium(III) Catalyst
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A rhodium(III)-catalyzed one-pot three-component reaction of N-methoxybenzamide, α-diazoester, and alkyne was developed, providing an alternative way to synthesize isoquinoline derivatives. Mechanistically, it is a relay catalysis, and the reaction occurred via successive O-alkylation and C-H activation processes, both of which were promoted by the same catalyst.
- Zhou, Chao,Jiang, Jijun,Wang, Jun
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supporting information
p. 4971 - 4975
(2019/09/03)
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- Method for preparing alpha-hydroxy acid
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The invention relates to the technical field of organic chemical asymmetric hydrogenation, specifically to a method for catalyzing an asymmetric hydrogenation alpha-ketonic acid compound to prepare achiral alpha-hydroxy acid compound. The method is simple in synthesis route, high in conversion rate and high in ee value.
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Paragraph 0050-0056
(2019/05/28)
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- Method for synthesizing novel uric acid lowering compound Arhalofenate intermediate
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The invention discloses a method for synthesizing a novel uric acid lowering compound Arhalofenate intermediate. The novel uric acid lowering compound Arhalofenate intermediate is (R)-chloromandelic acid, and is prepared by the following specific synthetic steps: taking a common organic solvent as a resolution solvent, taking racemic chloromandelic acid as a raw material, taking (R)-amine as a resolving agent, performing reflux preparation to obtain (R)-amine*(R)-chloromandelic acid, adding an acid to regulate the pH value, repeatedly extracting with ethyl acetate, merging the organic phase, adding anhydrous sodium sulfate for drying, performing suction filtration and desalting, and performing reduced pressure drying, thereby obtaining the (R)-chloromandelic acid with high optical purity.The method disclosed by the invention has the beneficial effects that the synthetic method is readily available in raw materials, excellent in separating speed and effect, high in resolution rate, lowin cost, simple and convenient in operation, low in requirements on production conditions and equipment and easy for industrial production.
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Paragraph 0020; 0023; 0025-0045
(2019/02/06)
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- Characterization of a new nitrilase from Hoeflea phototrophica DFL-43 for a two-step one-pot synthesis of (S)-β-amino acids
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A nitrilase from Hoeflea phototrophica DFL-43 (HpN) demonstrating excellent catalytic activity towards benzoylacetonitrile was identified from a nitrilase tool-box, which was developed previously in our laboratory for (R)-o-chloromandelic acid synthesis from o-chloromandelonitrile. The HpN was overexpressed in Escherichia coli BL21 (DE3), purified to homogeneity by nickel column affinity chromatography, and its biochemical properties were studied. The HpN was very stable at 30–40?°C, and highly active over a wide range of pH values (pH 6.0–10.0). In addition, the HpN could tolerate against several hydrophilic organic solvents. Steady-state kinetics indicated that HpN was highly active towards benzoylacetonitrile, giving a KM of 4.2?mM and a kcat of 170?s?1, the latter of which is ca. fivefold higher than the highest record reported so far. A cascade reaction for the synthesis of optically pure (S)-β-phenylalanine from benzoylacetonitrile was developed by coupling HpN with an ω-transaminase from Polaromonas sp. JS666 in toluene-water biphasic reaction system using β-alanine as an amino donor. Various (S)-β-amino acids could be produced from benzoylacetonitrile derivatives with moderate to high conversions (73–99%) and excellent enantioselectivity (> 99% ee). These results are significantly advantageous over previous studies, indicating a great potential of this cascade reaction for the practical synthesis of (S)-β-phenylalanine in the future.
- Zhang, Zhi-Jun,Cai, Rui-Feng,Xu, Jian-He
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p. 6047 - 6056
(2018/05/15)
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- Preparation method of DL-mandelic acid
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A preparation method of DL-mandelic acid comprises: using benzaldehyde, chloroform and sodium hydroxide as materials and beta-cyclodextrin as a catalyst, including the cyclodextrin via hydrophobic cavity structure that the beta-cyclodextrin has, forming d
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Paragraph 0012-0017
(2018/04/02)
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- Preparation method of mandelic acid
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The invention discloses a preparation method of mandelic acid. Benzaldehyde and Benzyltriethylammonium chloride are added into a trichloromethane solvent, a certain concentration of liquid alkali is dripped at a certain temperature, after the liquid alkal
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Paragraph 0018-0057
(2019/01/07)
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- Highly Efficient Deracemization of Racemic 2-Hydroxy Acids in a Three-Enzyme Co-Expression System Using a Novel Ketoacid Reductase
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Enantiopure 2-hydroxy acids (2-HAs) are important intermediates for the synthesis of pharmaceuticals and fine chemicals. Deracemization of racemic 2-HAs into the corresponding single enantiomers represents an economical and highly efficient approach for synthesizing chiral 2-HAs in industry. In this work, a novel ketoacid reductase from Leuconostoc lactis (LlKAR) with higher activity and substrate tolerance towards aromatic α-ketoacids was discovered by genome mining, and then its enzymatic properties were characterized. Accordingly, an engineered Escherichia coli (HADH-LlKAR-GDH) co-expressing 2-hydroxyacid dehydrogenase, LlKAR, and glucose dehydrogenase was constructed for efficient deracemization of racemic 2-HAs. Most of the racemic 2-HAs were deracemized to their (R)-isomers at high yields and enantiomeric purity. In the case of racemic 2-chloromandelic acid, as much as 300 mM of substrate was completely transformed into the optically pure (R)-2-chloromandelic acid (> 99% enantiomeric excess) with a high productivity of 83.8 g L?1 day?1 without addition of exogenous cofactor, which make this novel whole-cell biocatalyst more promising and competitive in practical application.
- Xue, Ya-Ping,Wang, Chuang,Wang, Di-Chen,Liu, Zhi-Qiang,Zheng, Yu-Guo
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- Discovery of 7-hydroxyaporphines as conformationally restricted ligands for beta-1 and beta-2 adrenergic receptors
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A series of (-)-nornuciferidine derivatives was synthesized and the non-natural enantiomer of the aporphine alkaloid was discovered to be a potent β1- and β2-adrenergic receptor ligand that antagonized isoproterenol and procaterol induced cyclic AMP increases from adenylyl cyclase, respectively. Progressive deconstruction of the tetracyclic scaffold to less complex cyclic and acyclic analogues revealed that the conformationally restricted (6a-R,7-R)-7-hydroxyaporphine 2 (AK-2-202) was necessary for efficient receptor binding and antagonism.
- Ku, Angela F.,Cuny, Gregory D.
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supporting information
p. 353 - 356
(2018/03/08)
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- Light-assisted preparation of a cyclodextrin-based chiral stationary phase and its separation performance in liquid chromatography
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A cyclodextrin-based chiral stationary phase (CD-CSP) is one of the most widely applied CSPs due to its powerful enantioseparation ability. In this study, a facile method was developed to prepare a CD-CSP via carboxyl methyl β-cyclodextrin (CD-COOH) and diazo-resin (DR). Monodisperse silica particles were synthesized using a modified St?ber method. Then DR and CD-COOH were coated on the silica particles via ionic bonding successively and UV light was finally used to couple silica, DR and CD-COOH and the ionic bonds turned into covalent bonds. The resultant CD-DR silica particles were characterized using Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA) and scanning electron microscopy (SEM). The enantioselectivity of the CD@SiO2 particles was explored in reversed phase high-performance liquid chromatography (RP-HPLC). Baseline separation of chiral drugs was achieved and the effects of separation parameters (elution mode, buffer and analyte mass) were investigated in detail. By using water soluble non-toxic DR to replace a highly toxic and moisture sensitive silane agent to modify silica microspheres, this light-assisted strategy can provide a green and effective technique to manufacture packing materials for enantioseparation applications.
- Tang, Qi,Yu, Bing,Gao, Lilong,Cong, Hailin,Zhang, Shuai
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supporting information
p. 1115 - 1120
(2018/02/06)
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- Enantioseparation of chiral mandelic acid derivatives by supercritical fluid chromatography
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Mandelic acid and its derivatives are important chiral analogs which are widely used in the pharmaceutical synthetic industry. The present study investigated the enantiomeric separation of six mandelic acids (mandelic acid, 2-chloromandelic acid, 3-chloromandelic acid, 4-chloromandelic acid, 4-bromomandelic acid, 4-methoxymandelic acid) on the Chiralpak AD-3 column by supercritical fluid chromatography. The influences of volume fraction of trifluoroacetic acid, type and percentage of modifier, column temperature, and backpressure on the separation efficiency were investigated. And the enantiomer elution order was determined. The results show that, for a given modifier, the retention factor, the separation factor, and the separation resolution decreased gradually with increasing the volume ratio of the modifier. At the same volume ratio of modifier, the retention factor of the mandelic acid and its derivatives increased in the order of methanol, ethanol, and isopropanol, except 3-chloromandelic acid. The separation factor and the separation resolution decreased with the increase of column temperature (below the temperature limit). The backpressure affected the enantioseparation process: As the backpressure increased, a corresponding decrease in retention factor was observed. Under the same chiral column conditions, the SFC method exhibited faster and more efficient separation with better enantioselectivity than the HPLC method.
- Ding, Jiawei,Zhang, Ming,Dai, Huixue,Lin, Chunmian
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p. 1245 - 1256
(2018/09/25)
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- Discovery of a diverse set of esterases from hot spring microbial mat and sea sediment metagenomes
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Esterases are an important group of biocatalysts for synthetic organic chemistry. Functional metagenomics allows discovery of novel biocatalysts by providing access to the gene pool of the microbial community of a habitat. Two metagenomic libraries representing the gene pool of sea sediment and hot spring microbial mat were constructed. Functional screening of these libraries resulted in the isolation of total 8 clones with tributyrin hydrolytic activity. Sequence analysis revealed 10 putative lipolytic proteins with 42–99% homology to the protein sequences in the databases, nine of which represented six known esterase families. Four of the encoded proteins represented Family V and amongst others, one each represented the Family VIII, pectin acetylesterase, enterobactin esterase, G-D-S-L family and OsmC domain containing esterase. One unusual lipolytic protein possessed poly-(3-hydroxybutyrate) depolymerase domain fused to lipase/esterase domain. Two phylogenetically related esterases (MLC3 and SLC5) belonging to family V were expressed and purified to homogeneity. The enzymes exhibited environment-adapted temperature optimum and thermostability. MLC3 was able to stereoselectively hydrolyze R-methyl mandelate to produce R-mandelic acid, an important chiral building block, which suggests MLC3 has potential commercial application.
- Ranjan, Ravi,Yadav, Manish Kumar,Suneja, Garima,Sharma, Rakesh
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p. 572 - 581
(2018/08/03)
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- Method for preparing mandelic acid from styrene oxide
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The invention provides a method for preparing mandelic acid from styrene oxide. The preparation method comprises the following steps: preparing phenyl glycol from styrene oxide through hydration under the catalysis of a NY-series catalyst; and introducing air for selective oxidation of mandelic acid from phenyl glycol under the action of an active carbon-loaded Pd-Au catalyst. The preparation method is characterized in that raw materials are mainly composed of styrene oxide, the NY-series catalyst and the active carbon-loaded Pd-Au catalyst. The preparation method for mandelic acid uses cheap and easily available raw materials and is simple in process, mild in conditions and high in product yield and product purity.
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Paragraph 0041; 0044; 0047; 0050; 0053; 0056
(2017/10/07)
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- Chemoenzymatic Preparation of Enantiomerically Enriched (R)-(–)-Mandelic Acid Derivatives: Application in the Synthesis of the Active Agent Pemoline
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The enantioselective resolution of several racemic derivatives of mandelic acid methyl ester catalyzed by lipases from Pseudomonas fluorescens (Amano AK) or Burkholderia cepacia (Amano PS-C II and Amano PS-IM) has been achieved. A gram-scale lipase-mediated kinetic resolution approach has been developed that allows the facile synthesis of the corresponding methyl (R)-(–)-mandelates with excellent enantiomeric excesses (up to >99 % ee) and reaction enantioselectivity (E values up to >200). The dopaminergic agent pemoline, used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy, was synthesized with 98 % ee in a straightforward route by condensing the prepared methyl (R)-(–)-mandelate with guanidine hydrochloride under basic conditions. The desired (R)-(+)-pemoline in optically pure form (>99 % ee) was obtained after two recrystallizations from ethanol. However, it was confirmed by chiral HPLC that optically active pemoline undergoes racemization in methanol solution.
- Potera?a, Marcin,Dranka, Maciej,Borowiecki, Pawe?
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p. 2290 - 2304
(2017/05/01)
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- The Synthesis of Chiral α-Aryl α-Hydroxy Carboxylic Acids via RuPHOX-Ru Catalyzed Asymmetric Hydrogenation
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A ruthenocenyl phosphino-oxazoline-ruthenium complex (RuPHOX?Ru) catalyzed asymmetric hydrogenation of α-aryl keto acids has been successfully developed, affording the corresponding chiral α-aryl α-hydroxy carboxylic acids in high yields and with up to 97% ee. The reaction could be performed on a gram scale with a relatively low catalyst loading (up to 5000 S/C) and the resulting products can be transformed to several chiral building blocks, biologically active compounds and chiral drugs. (Figure presented.).
- Guo, Huan,Li, Jing,Liu, Delong,Zhang, Wanbin
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p. 3665 - 3673
(2017/09/11)
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- Reductive carboxylation of aromatic esters by electron transfer from magnesium metal
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Magnesium-promoted reductive carboxylation of ethyl benzoate in the presence of chlorotrimethylsilane in N,N-dimethylformamide brought about a new carbon-carbon bond formation between the carbonyl carbon atom and carbon dioxide to give the corresponding benzoylformic acid in good yield. It is noteworthy that only ethyl benzoates with substituents at the meta-position were converted into benzoylformic acid derivatives. Moreover, no mandelic acid was detected even under the reductive conditions. This result indicates that benzoylformic acid was obtained after hydrolysis of a carboxylated intermediate, which would be alive as a stabilized structure in the reaction media.
- Maekawa, Hirofumi,Okawara, Hikaru,Murakami, Taro
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supporting information
p. 206 - 209
(2016/12/28)
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- Benzyl isobornyl amines: a simple and practical class of NMR discriminating agents for effective chiral recognition of acids
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The design and synthesis of a few simple N-benzyl derivatives of isobornyl amine is presented. The derivatives have been assessed as chiral solvating agents for effective discrimination of the signals of some acids in NMR analysis. The single crystal X-ray analysis of the salts of (R)-mandelic acid with two of the title derivatives help to understand the supramolecular interactions and assign the induced chemical shifts in 1H NMR analysis. The title derivative is found to be suitable for quantitative determination of the enantiomeric excess of unknown enantiomeric purity as well as being efficient in resolving racemic mandelic acid.
- Kannappan, Jayaraman,Khanvilkar, Aditya N.,Upadhyay, Gourav M.,Bedekar, Ashutosh V.
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p. 1297 - 1303
(2017/10/06)
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- Optical resolution and mechanism using enantioselective cellulose, sodium alginate and hydroxypropyl-β-cyclodextrin membranes
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Chiral solid membranes of cellulose, sodium alginate, and hydroxypropyl-β-cyclodextrin were prepared for chiral dialysis separations. After optimizing the membrane material concentrations, the membrane preparation conditions and the feed concentrations, enantiomeric excesses of 89.1%, 42.6%, and 59.1% were obtained for mandelic acid on the cellulose membrane, p-hydroxy phenylglycine on the sodium alginate membrane, and p-hydroxy phenylglycine on the hydroxypropyl-β-cyclodextrin membrane, respectively. To study the optical resolution mechanism, chiral discrimination by membrane adsorption, solid phase extraction, membrane chromatography, high-pressure liquid chromatography ultrafiltration were performed. All of the experimental results showed that the first adsorbed enantiomer was not the enantiomer that first permeated the membrane. The crystal structures of mandelic acid and p-hydroxy phenylglycine are the racematic compounds. We suggest that the chiral separation mechanism of the solid membrane is “adsorption – association – diffusion,” which is able to explain the optical resolution of the enantioselective membrane. This is also the first report in which solid membranes of sodium alginate and hydroxypropyl-β-cyclodextrin were used in the chiral separation of p-hydroxy phenylglycine.
- Yuan, Li-Ming,Ma, Wei,Xu, Mei,Zhao, Hui-Lin,Li, Yuan-Yuan,Wang, Rui-Lin,Duan, Ai-Hong,Ai, Ping,Chen, Xue-Xian
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p. 315 - 324
(2017/05/29)
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- Investigating Substrate Scope and Enantioselectivity of a Defluorinase by a Stereochemical Probe
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The possibility of a double Walden inversion mechanism of the fluoracetate dehalogenase FAcD (RPA1163) has been studied by subjecting rac-2-fluoro-2-phenyl acetic acid to the defluorination process. This stereochemical probe led to inversion of configuration in a kinetic resolution with an extremely high selectivity factor (E > 500), showing that the classical mechanism involving SN2 reaction by Asp110 pertains. The high preference for the (S)-substrate is of synthetic value. Wide substrate scope of RPA1163 in such hydrolytic kinetic resolutions can be expected because the reaction of the even more sterically demanding rac-2-fluoro-2-benzyl acetic acid proceeded similarly. Substrate acceptance and stereoselectivity were explained by extensive molecular modeling (MM) and molecular dynamics (MD) computations. These computations were also applied to fluoroacetic acid itself, leading to further insights.
- Wang, Jian-Bo,Ilie, Adriana,Yuan, Shuguang,Reetz, Manfred T.
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p. 11241 - 11247
(2017/08/21)
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- Desyl and phenacyl as versatile, photocatalytically cleavable protecting groups: A classic approach in a different (visible) light
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A highly efficient, catalytic strategy for the deprotection of classical phenacyl (Pac) as well as desyl (Dsy) protection groups has been developed using visible light photoredox catalysis. The deliberate use of a neutral two-phase acetonitrile/water mixture with K3PO4 applying catalytic amounts of [Ru(bpy)3](PF6)2 in combination with ascorbic acid is the key to this truly catalytic deprotection of Pac- and Dsy-protected carboxylic acids. Our mild yet robust protocol allows for fast and selective liberation of the free carboxylic acids in very good to quantitative yields, while only low catalyst loadings (1 mol %) are required. Both Pac and Dsy, easily introduced from commercially available precursors, can be applied for the direct protection of carboxylic acids and amino acids, offering orthogonality to a great variety of other common protecting groups. We further demonstrate the general applicability and versatility of these formerly underrated protecting groups in combination with our catalytic cleavage conditions, as underscored by the gained high functional group tolerance. Moreover, this method could successfully be adapted to the requirements of solidphase synthesis. As a proof of principle for an efficient visible light, photocatalytic linker cleavage, a Boc-protected tripeptide was split off from commercially available brominated Wang resin.
- Speckmeier, Elisabeth,Zeitler, Kirsten
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p. 6821 - 6826
(2017/11/06)
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- Production Of Enantiopure alpha-Hydroxy Carboxylic Acids From Alkenes By Cascade Biocatalysis
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The invention provides compositions comprising an alkene epoxidase and a selective epoxide hydrolase, such as a recombinant microorganism comprising a first heterologous nucleic acid encoding an alkene epoxidase and a second heterologous nucleic acid encoding a selective epoxide hydrolase. Exemplary alkene epoxidases include StyAB, while exemplary selective epoxide hydrolases include epoxide hydrolases from Sphingomonas, Solanum tuberosum, or Aspergillus. The invention also provides non-toxic methods of making enantiomerically pure vicinal diols or enantiomerically pure alpha-hydroxy carboxylic acids using these compositions and microorganisms.
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Paragraph 0074-0076
(2016/05/02)
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- Asymmetric hydrogenation reaction of alpha-ketoacids compound
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The invention relates to the technical field of organic chemistry, especially to an asymmetric hydrogenation reaction of an alpha-ketoacids compound. The asymmetric hydrogenation reaction comprises a scheme shown in the description. In the scheme, R1 is phenyl, substituted phenyl, naphthyl, substituted naphthyl, C1-C6 alkyl, or aralkyl; a substituent group is C1-C6 alkyl, C1-C6 alkoxy, or halogen; and the number of the substituent group is 1-3. In the scheme, M is a chiral spiro-pyridylamino phosphine ligand iridium complex having a structure shown in the description. In the structure, R is hydrogen, 3-methyl, 4-tBu, or 6-methyl.
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Paragraph 0033; 0037
(2016/10/10)
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- Copper encapsulated alkaloids composite: An effective heterogeneous catalyst for electrocatalytic asymmetric hydrogenation
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A novel heterogeneous catalyst, alkaloid@Cu was prepared by the entrapment of commercially purchased alkaloids within non-noble metallic copper nanoparticles. This composite was compacted into a coin and directly used as cathode for electrocatalytic asymmetric hydrogenation of aromatic ketones. Using water as hydrogen source, optically active alcohols with 71% ee value and 93% yield were obtained under very mild conditions.
- Yang, Heng-Pan,Fen, Qiu,Wang, Huan,Lu, Jia-Xing
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- Easy stabilization of interfacially activated lipases using heterofunctional divinyl sulfone activated-octyl agarose beads. Modulation of the immobilized enzymes by altering their nanoenvironment
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Octyl-agarose is a support that permits the one step immobilization, stabilization and purification of lipases. However, the enzyme may be released from the support under drastic conditions. This paper describes a new heterofunctional support, octyl agarose beads activated with divinyl sulfone, that has proved to be useful to produce very stable and active biocatalysts of lipases from Candida rugosa (CRL), Rhizomucor miehei (RML) and Thermomyces lanuginosus (TLL), able to work under any reaction conditions without risking enzyme desorption. The three enzymes failed in immobilization on glyoxyl-octyl supports for different reasons. The immobilization at pH 5 permitted to keep the good properties of octyl agarose. Further incubation at pH 8 permitted to establish at least one covalent enzyme-support bond per enzyme molecule (preventing the risk of enzyme desorption), avoiding the inactivation produced at pH 10, and the final result is that all three new biocatalysts are more active than the octyl-glyoxyl counterparts and much more stable (e.g.; 20 using CRL). The end of the enzyme-support reaction was achieved via blocking the vinylsulfone groups with different nucleophiles (cationic, anionic, hydrophobic, etc). This not only determined the final enzyme stability, but also the activity, selectivity and even specificity of the different immobilized preparations.
- Albuquerque, Tiago L.De,Rueda, Nazzoly,Dos Santos, Jose C.S.,Barbosa, Oveimar,Ortiz, Claudia,Binay, Baris,?zdemir, Ece,Gon?alves, Luciana R.B.,Fernandez-Lafuente, Roberto
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p. 865 - 874
(2016/06/09)
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- The pH-dependency of diastereomeric salt resolutions with amphoteric resolving agents
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We have analysed the role of pH in the diastereomeric resolution of racemic mandelic acid with (S)-phenylalanine and (R)-3-(aminomethyl)- 5-methylhexanoic acid [(R)-Pregabalin] enantiomers. The adjusted pH had an effect on the optical purity and yield of
- Szeleczky, Zsolt,Bagi, Péter,Pálovics, Emese,Faigl, Ferenc,Fogassy, Elemér
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- Chiral Polymers of Intrinsic Microporosity: Selective Membrane Permeation of Enantiomers
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Following its resolution by diastereomeric complexation, 5,5′,6,6′-tetrahydroxy-3,3,3′,3′-tetramethyl-1,1′-spirobisindane (TTSBI) was used to synthesize a chiral ladder polymer, (+)-PIM-CN. (+)-PIM-COOH was also synthesized by the acid hydrolysis of (+)-PIM-CN. Following characterization, both (+)-PIM-CN and (+)-PIM-COOH were solvent cast directly into semipermeable membranes and evaluated for their ability to enable the selective permeation of a range of racemates, including mandelic acid (Man), Fmoc-phenylalanine, 1,1′-bi-2-naphthol (binol), and TTSBI. High ee values were observed for a number of analytes, and both materials exhibited high permeation rates. A selective diffusion–permeation mechanism was consistent with the results obtained with these materials. Their high permeability, processability, and ease of chemical modification offer considerable potential for liquid-phase membrane separations and related separation applications.
- Weng, Xilun,Baez, José E.,Khiterer, Mariya,Hoe, Madelene Y.,Bao, Zongbi,Shea, Kenneth J.
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p. 11214 - 11218
(2016/07/06)
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- Preparation method of (1R,2S)-1-phenyl-2-(1-pyrrolidyl)-1-propanol
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The invention discloses a preparation method of (1R,2S)-1-phenyl-2-(1-pyrrolidyl)-1-propanol. According to the preparation method, DL-1-phenyl-2-(1-pyrrolidyl)-1-acetone is taken as a starting material and subjected to resolution, racemization and reduction, and (1R,2S)-1-phenyl-2-(1-pyrrolidyl)-1-propanol is prepared. The yield of one-time resolution is higher than 35%, a resolving agent is easy to recover, and the recovery rate is higher than 90%; the racemization process is performed under the slightly alkaline condition, and the racemization yield is higher; the yield of (1R,2S)-1-phenyl-2-(1-pyrrolidyl)-1-propanol obtained through reduction is higher than 85%. The preparation method has the advantages of mild reaction conditions, stable process, high product optical purity, low cost, high production safety and the like.
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Paragraph 0041
(2016/10/31)
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- An efficient enzymatic aminolysis for kinetic resolution of aromatic α-hydroxyl acid in non-aqueous media
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A new and highly efficient enzymatic aminolysis approach for kinetic resolution of aromatic α-hydroxy acid in non-aqueous media has been developed. The corresponding α-hydroxyl acid ester was employed as the substrate, and commercially available Candida antarctica lipase B is used as the biocatalyst, anhydrous ammonia is the resolving agent. Reactions can be proceeded smoothly in organic solvent at ambient temperatures. High concentration of substrate is allowed due to the application of organic media and the products are obtained in yields of up to 49% with ee values of up to 99%, and with E value of >300, representing an appealing and promising protocol for large-scale preparations.
- Chen, Shan,Liu, Fuyan,Zhang, Kuan,Huang, Hansheng,Wang, Huani,Zhou, Jiaying,Zhang, Jing,Gong, Yiwei,Zhang, Dela,Chen, Yiping,Lin, Chang,Wang, Bo
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p. 5312 - 5314
(2016/11/16)
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- A high-throughput screening method for determining the substrate scope of nitrilases
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Nitrile compounds are intermediates in the synthesis of pharmaceuticals such as atorvastatin. We have developed a chromogenic reagent to screen for nitrilase activity as an alternative to Nessler's reagent. It produces a semi-quantifiable blue colour and hydrolysis of 38 nitrile substrates by 23 nitrilases as cell-free extracts has been shown. This journal is
- Black, Gary W.,Brown, Nicola L.,Perry, Justin J. B.,Randall, P. David,Turnbull, Graeme,Zhang, Meng
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supporting information
p. 2660 - 2662
(2015/03/05)
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- Solid phase behavior in the chiral systems of various 2-hydroxy-2-phenylacetic acid (mandelic acid) derivatives
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The solid phase behavior of a series of monosubstituted F-, Cl-, Br-, I-, and CH3- and two 2,4-halogen-disubstituted 2-hydroxy-2-phenylacetic acid (mandelic acid) derivatives was investigated. The study includes detailed information about melting temperature, melting enthalpy, X-ray diffraction data, as well as selected binary phase diagrams of the respective chiral systems. Aside from the known metastable conglomerate 2-chloromandelic acid, evidence for two more metastable conglomerates was found.
- Von Langermann, Jan,Temmel, Erik,Seidel-Morgenstern, Andreas,Lorenz, Heike
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p. 721 - 728
(2015/03/30)
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- Improved performance of lipases immobilized on heterofunctional octyl-glyoxyl agarose beads
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A new heterofunctional support, octyl-glyoxyl agarose, is proposed in this study. The supports were prepared by simple periodate oxidation of the commercial octyl-agarose, introducing 25 μmol of glyoxyl groups per wet gram of support. This support was assayed with three different lipases (those from Candida antarctica (form B), Thermomyces lanuginosus (TLL) or Rhizomucor miehei) and the artificial phospholipase Lecitase Ultra. Used at pH 7, the new support maintained as first immobilization step the lipase interfacial activation. Thus, it was possible to have the purification and immobilization of the enzyme in one step. Moreover, stabilization of the open form of the lipase was achieved. The covalent enzyme/support bonds cannot be obtained if the immobilized enzyme was not incubated at alkaline pH value. This incubation at pH 10 of the previously immobilized enzymes produced a smaller decrease in enzyme activity when compared to the direct immobilization of the enzymes on glyoxyl-agarose at pH 10, because the immobilization via interfacial activation promoted a stabilization of the lipases. Except in the case of TLL (covalent attachment involved 70% of the enzyme molecules), covalent immobilization yield was over 80%. The non-covalent attached enzyme molecules were discarded by washings with detergent solutions and the new biocatalysts were compared to the octyl-agarose immobilized enzymes. While the stability in thermal and organic solvents inactivations was increased for Lecitase Ultra, CALB and RML, TLL improved its stability in organic media but its thermal stability decreased after covalent attachment of the interfacially activated enzyme. This stabilization resulted in octyl-glyoxyl-lipase preparations which presented higher activity in the presence of organic solvents. Finally, while octyl-agarose released enzyme molecules after incubation at high temperatures or in the presence of organic solvents and detergents, the covalently immobilized enzyme remained attached to the support even after boiling the enzyme in SDS, eliminating the risks of product contamination.
- Rueda, Nazzoly,Dos Santos, Jose C. S.,Torres, Rodrigo,Ortiz, Claudia,Barbosa, Oveimar,Fernandez-Lafuente, Roberto
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p. 11212 - 11222
(2015/02/05)
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- Alkaloid-induced asymmetric hydrogenation on a Cu nanoparticle cathode by electrochemical conditions
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Copper nanoparticles were prepared in an aqueous solution, compacted into a coin, and used as a cathode for asymmetric hydrogenation by the electrochemical method for the first time. A good ee value and excellent yield were obtained under mild conditions. Electrochemical conditions were crucial for alkaloid adsorption on metallic Cu, which is a key process of asymmetric induction. Furthermore, the ee value was linear with an adsorption amount.
- Yang, Heng-Pan,Wang, Huan,Lu, Jia-Xing
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- Nitrilases
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The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition, methods of designing new nitrilases and methods of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.
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Paragraph 0351
(2015/09/22)
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- Nitrilases, nucleic acids encoding them and methods for making and using them
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The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition methods of designing new nitrilases and method of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.
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Page/Page column 70
(2016/01/09)
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- Directed evolution of nitrilase PpL19 from Pseudomonas psychrotolerans L19 and identification of enantiocomplementary mutants toward mandelonitrile
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Nitrilase PpL19 from Pseudomonas psychrotolerans L19 can hydrolyze racemic mandelonitrile to (S)-mandelic acid with an enantiomeric excess (ee) value of 52.7%. In this study, random mutagenesis combined with site-directed mutagenesis was performed to iden
- Sun, Huihui,Wang, Hualei,Gao, Wenyuan,Chen, Lifeng,Wu, Kai,Wei, Dongzhi
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p. 820 - 825
(2015/12/18)
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- Asymmetric synthesis of optically active methyl-2-benzamido-methyl-3-hydroxy-butyrate by robust short-chain alcohol dehydrogenases from Burkholderia gladioli
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Three short-chain alcohol dehydrogenases from Burkholderia gladioli were discovered for their great potential in the dynamic kinetic asymmetric transformation of methyl 2-benzamido-methyl-3-oxobutanoate, and their screening against varied organic solvents and substrates. This is the first report of recombinant enzymes capable of achieving this reaction with the highest enantio- and diastereo-selectivity.
- Chen, Xiang,Liu, Zhi-Qiang,Huang, Jian-Feng,Lin, Chao-Ping,Zheng, Yu-Guo
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p. 12328 - 12331
(2015/07/27)
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