10421-85-9Relevant articles and documents
The effect of SDE on the separation of diastereomeric salts: A case study for the resolution of mandelic acid derivatives with Pregabalin
Szeleczky, Zsolt,Bagi, Péter,Pálovics, Emese,Fogassy, Elemér
, p. 1095 - 1099 (2014)
A resolution method has been elaborated for mandelic acid and 2-chloromandelic acid applying the (R)-(-)-3-(aminomethyl)-5-methylhexanoic acid (Pregabalin) as the resolving agent. The formation of the corresponding diastereomers was kinetically controlled. This observation was rationalized by the behavior of enantiomeric mixtures of mandelic acid, 2-chloromandelic acid, and 3-(aminomethyl)-5-methylhexanoic acid. It was found that the eutectic composition of Pregabalin influenced the diastereomeric excess of the diastereomers formed under kinetic control.
One-pot, single-step deracemization of 2-hydroxyacids by tandem biocatalytic oxidation and reduction
Xue, Ya-Ping,Zheng, Yu-Guo,Zhang, Ya-Qin,Sun, Jing-Lei,Liu, Zhi-Qiang,Shen, Yin-Chu
, p. 10706 - 10708 (2013)
A facile and efficient one-pot, single-step method for deracemizing a broad range of 2-hydroxyacids to (R)-2-hydroxyacids was established by combination of resting cells of an (S)-hydroxyacid dehydrogenase-producing microorganism and an (R)-ketoacid reductase-producing microorganism.
Enantioseparation of chiral mandelic acid derivatives by supercritical fluid chromatography
Ding, Jiawei,Zhang, Ming,Dai, Huixue,Lin, Chunmian
, p. 1245 - 1256 (2018)
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.
The phase behavior and crystallization of 2-chloromandelic acid: The crystal structure of the pure enantiomer and the behavior of its metastable conglomerate
Lorenz, Heike,Von Langermann, Jan,Sadiq, Ghazla,Seaon, Colin C.,Davey, Roger J.,Seidel-Morgenstern, Andreas
, p. 1549 - 1556 (2011)
Crystallization of racemic 2-chloromandelic acid yields a metastable conglomerate in addition to a more stable racemic compound. The crystal structure of the pure enantiomer is reported and the relative stability of the racemic compound and conglomerate was determined at both room temperature and the melting point. Crystallizations from melt and solution are shown to offer potential crystallization pathways to the conglomerate, provided crystallization of the racemic compound can be avoided.
Efficient production of (R)-o-chloromandelic acid by recombinant escherichia coli cells harboring nitrilase from burkholderia cenocepacia J2315
Wang, Hualei,Sun, Huihui,Gao, Wenyuan,Wei, Dongzhi
, p. 767 - 773 (2014)
A solvent engineering approach and an extended fed-batch reaction mode were introduced to increase the activity and enantioselectivity and alleviate the substrate inhibition of nitrilase BCJ2315 from Burkholderia cenocepacia J2315 toward o-chloromandelonitrile. Among the seven water-miscible organic solvents tested, ethanol (30%, v/v) demonstrated the highest reaction conversion (55.7%) and enantioselectivity (enantiomeric excess, 98.2% ee) compared with those of the control [which did not contain any organic solvent (13% and 89.2%, respectively)] and was thus chosen as the suitable cosolvent. In the extended fed-batch reaction mode, o-chloromandelonitrile (solubilized in ethanol, 5 M) was continuously fed into the reaction mixture containing ethanol as cosolvent (20%, v/v) to ensure an optimal reaction rate by adjusting the feeding rate and simultaneously increasing the enantioselectivity due to the increased concentration of ethanol. Finally, a maximum of 415 mM of product was produced with an enantiomeric excess value of 97.6% ee. The hydrolysis process was easily scaled up to 2 L, demonstrating that the described biocatalytic process was rationally designed and could be applied further on an industrial scale.
β-Cyclodextrin-teba: A new catalyst system for selective synthesis of α-hydroxyacids
Zhou,Yuan,Xie
, p. 43 - 46 (1994)
The presence of β-cyclodextrin (β-CD) and triethylbenzyl ammonium chloride (TEBA) favors the one-pot reaction of aromatic aldehydes, chloroform and sodium hydroxide to give α- hydroxyarylacetic acids in 81% ~ 89% yields.
Efficient preparation of (R)-2-chloromandelic acid via a recycle process of resolution
Hu, Yu,Wu, Chang,Wu, Xue-Ying,Li, Shao-Lei,Sun, Xiao-Xia,Tang, Ze-Biao
, p. 281 - 285 (2015)
Efficient preparation of (R)-2-chloromandelic acid (R)-1 based on a recycle process of resolution is described. In the process, the desired (R)-1 was obtained by coordination-mediated resolution with D-O,O′-di-(p-toluoyl)-tartaric acid in the presence of Ca2+. Meanwhile, the undesired (S)-1 could be racemized in the presence of sodium hydroxide and the product was suitable for further resolution. A carbanion mechanism for the racemization of (S)-1 is proposed.
Biocatalytic racemization of aliphatic, arylaliphatic, and aromatic α-hydroxycarboxylic acids
Glueck, Silvia M.,Pirker, Monika,Nestl, Bettina M.,Ueberbacher, Barbara T.,Larissegger-Schnell, Barbara,Csar, Katrin,Hauer, Bernhard,Stuermer, Rainer,Kroutil, Wolfgang,Faber, Kurt
, p. 4028 - 4032 (2005)
Biocatalytic racemization of a range of aliphatic, (aryl)aliphatic, and aromatic α-hydroxycarboxylic acids was accomplished by using whole resting cells of a range of Lactobacillus spp. The mild (physiological) reaction conditions ensured an essentially "clean" isomerization in the absence of side reactions, such as elimination or decomposition. Whereas straight-chain aliphatic 2-hydroxy-carboxylic acids were racemized with excellent rates (up to 85% relative to lactate), steric hindrance was observed for branched-chain analogues. Good rates were observed for aryl-alkyl derivatives, such as 3-phenyllactic acid (up to 59%) and 4-phenyl-2-hydroxybutanoic acid (up to 47%). In addition, also mandelate and its o-chloro analogue were accepted at a fair rate (45%). This biocatalytic racemization represents an important tool for the deracemization of a number of pharmaceutically important building blocks.
Design of nitrilases with superior activity and enantioselectivity towards sterically hindered nitrile by protein engineering
Xue, Ya-Ping,Shi, Cheng-Ci,Xu, Zhe,Jiao, Biao,Liu, Zhi-Qiang,Huang, Jian-Feng,Zheng, Yu-Guo,Shen, Yin-Chu
, p. 1741 - 1750 (2015)
Abstract The enantioselective hydrolysis of ortho-chloromandelonitrile with nitrilase is one of the most attractive approaches to prepare (R)-ortho-chloromandelic acid. To date, efforts to develop this nitrilase-mediated process were plagued by either insufficient eep (enantiomeric excess of product) or low activity due to the steric hindrance from the ortho-substituted substrate. To improve the nitrilase potential for producing (R)-ortho-chloromandelic acid, an enhancement of both activity and enantioselectivity towards sterically hindered nitriles would be highly desirable. Molecular docking of the (R)-ortho-chloromandelonitrile into the active site of wild-type 2A6 nitrilase (nitA) allowed the identification of proximal nitA active site residues. Several residues (52, 132, 189 and 190) were selected as targets for single and double point mutation to improve nitA activity and enantioselectivity towards ortho-chloromandelonitrile. Targeted mutagenesis yielded several nitA variants with superior activity and enantioselectivity. The best mutant T132A/F189T exhibited a 4.37-fold higher specific activity (7.39 U/mg) towards ortho-chloromandelonitrile than the wild-type nitA. More importantly, the enantioselectivity (E) was improved from 17.34 to >200, resulting in a highly enantiopure product. Molecular docking experiments further support the enhanced activity and enantioselectivity shown experimentally and the structural effects of this amino acid substitution on the active site of nitA are provided. The amino acids at sites 189 and 132 determine the activity and enantioselectivity towards ortho-chloromandelonitrile. With mutant T132A/F189T as a catalyst, a maximum of 450 mM of (R)-ortho-chloromandelic acid was produced with a 90% conversion and >99% eep within 3 h. This is the first time that a high productivity of (R)-ortho-chloromandelic acid of up to 671.76 g L-1d-1 using a nitrilase-mediated approach is reported. The engineered T132A/F189T variant represents a promising and competitive biocatalyst for practical application in synthesizing (R)-ortho-chloromandelic acid.
Improved apparent enantioselectivity of a hydrolase by sequential hydrolysis and racemization
Gu, Jiali,Ye, Lidan,Guo, Fei,Lv, Xiaomei,Lu, Wenqiang,Yu, Hongwei
, p. 1489 - 1491 (2015)
Further improvement of the enantioselectivity of hydrolases with moderate enantioselectivity is of important significance to fulfill the requirement in industrial application. Herein, a strategy based on sequential hydrolysis and racemization was adopted, using esterase BioH from Escherichia coli as an example. After coupling with a mandelate racemase, the E value of esterase BioH toward methyl (S)-o-chloromandelate was enhanced from 73 to 162, demonstrating the effectiveness of this strategy.
