95537-36-3Relevant articles and documents
Synthesis method of quaternary amine inner salt
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Paragraph 0078; 0079, (2019/01/14)
The invention discloses a synthesis method of quaternary amine inner salt. The synthesis method comprises the following steps: (a) reduction reaction: taking a compound having a structure shown as theformula I as a raw material, carrying out a reduction reaction among the compound, an apoenzyme, a dehydrogenase and a coenzyme in monosaccharide within a certain pH range, removing enzymes with active carbon and performing rectification, so as to obtain a reduced product shown in the original specification, wherein X represents one of chlorine, bromine and iodine in halogens, and R represents one of a saturated alkyl or an unsaturated alkyl; (b) synthesis of the quaternary amine inner salt: carrying out a reaction between an obtained product and trimethylamine under a strong base condition to obtain quaternary amine hydrochloride, exchanging the quaternary amine hydrochloride in ion exchange resin to remove halide ions, performing concentration and refining a concentrated product with alcohol and acetone, so as to obtain the quaternary amine inner salt. The synthesis method has the advantages of being high in yield in each step, simple to operate and mild in reaction conditions, effectively removing enzyme residues by introducing a chiral structure with a high-selectivity enzymatic method, avoiding a reagent with high toxicity and high pollution by utilizing renewable resin for desalting, obtaining the high-purity product, being suitable for industrial production and the like.
Cloning, expression and enzymatic characterization of an aldo-keto reductase from Candida albicans XP1463
Wang, Ya-Jun,Liu, Xiao-Qing,Luo, Xi,Liu, Zhi-Qiang,Zheng, Yu-Guo
, p. 44 - 50 (2015/09/15)
An aldo-keto reductase encoding gene caakr was cloned from Candida albicans XP1463 (CCTCC M 2014382), and heterologously expressed in Escherichia coli. The aldo-keto reductase CaAKR is NADH-dependent with a molecular weight of approximately 38.6 kDal including a His6-Tag. It is active and stable at 30°C and pH 7.0. The maximal reaction rate (Vmax), apparent Michaelis-Menten constant (Km) and catalytic constant (kcat) for t-butyl 6-cyano-(5R)-hydroxy-3-oxohexanoate ((R)-1a) were 11.50 mmol/L min, 1.91 mmol/L and 218.50 min-1. Besides atorvastatin's chiral synthon t-butyl 6-cyano-(3R,5R)- dihydroxy hexanoate ((R,R)-1b), it can synthesize N,N-2-dimethyl-(3S)-hydroxy-3-(2-thienyl)-1-propanine ((S)-9b) and methyl 1-[E]-2-[3-[3-[2-(7-chloro-2-quinoliny) ethenyl] phenyl]-(3S)-hydroxy propy] benzoate ((S)-10b), the chiral intermediates of duloxetine and montelukast, displaying potential applications in pharmaceutical industry. 2015 Elsevier B.V. All rights reserved.
Asymmetric synthesis of optically active methyl-2-benzamido-methyl-3-hydroxy-butyrate by robust short-chain alcohol dehydrogenases from Burkholderia gladioli
Chen, Xiang,Liu, Zhi-Qiang,Huang, Jian-Feng,Lin, Chao-Ping,Zheng, Yu-Guo
, p. 12328 - 12331 (2015/07/27)
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.
Facile access to chiral alcohols with pharmaceutical relevance using a ketoreductase newly mined from Pichia guilliermondii
Xu, Guochao,Yu, Huilei,Xu, Jianhe
, p. 349 - 354 (2013/08/22)
Chiral secondary alcohols with additional functional groups are frequently required as important and valuable synthons for pharmaceuticals, agricultural and other fine chemicals. With the advantages of environmentally benign reaction conditions, broad reaction scope, and high stereoselectivity, biocatalytic reduction of prochiral ketones offers significant potential in the synthesis of optically active alcohols. A CmCR homologous carbonyl reductase from Pichia guilliermondii NRRL Y-324 was successfully overexpressed. Substrate profile characterization revealed its broad substrate specificity, covering aryl ketones, aliphatic ketones and ketoesters. Furthermore, a variety of ketone substrates were asymmetrically reduced by the purified enzyme with an additionally NADPH regeneration system. The reduction system exhibited excellent enantioselectivity (>99% ee) in the reduction of all the aromatic ketones and ketoesters, except for 2-bromoacetophenone (93.5% ee). Semi-preparative reduction of six ketones was achieved with high enantioselectivity (>99% ee) and isolation yields (>80%) within 12 h. This study provides a useful guidance for further application of this enzyme in the asymmetric synthesis of chiral alcohol enantiomers. Copyright
Experimental and computation studies on Candida antarctica lipase B-catalyzed enantioselective alcoholysis of 4-bromomethyl-β-lactone leading to enantiopure 4-bromo-3-hydroxybutanoate
Lim, Jung Yun,Jeon, Nan Young,Park, A-Reum,Min, Bora,Kim, Bum Tae,Park, Seongsoon,Lee, Hyuk
, p. 1808 - 1816 (2013/07/19)
Both enantiomers of optically pure 4-bromo-3-hydroxybutanoate, which is an important chiral building block in the syntheses of various biologically active compounds including statins, were synthesized from rac-4-bromomethyl-β- lactone through kinetic resolution. Candida antarctica lipase B (CAL-B) enantioselectively catalyzes the ring opening of the β-lactone with ethanol to yield ethyl (R)-4-bromo-3-hydroxybutanoate with high enantioselectivity (E>200). The unreacted (S)-4-bromomethyl-β-lactone was converted to ethyl (S)-4-bromo-3-hydroxybutanoate (>99% ee), which can be further transformed to ethyl (R)-4-cyano-3-hydroxybutanoate, through an acid-catalyzed ring opening in ethanol. Molecular modeling revealed that the stereocenter of the fast-reacting enantiomer, (R)-bromomethyl-β-lactone, is ～2 A from the reacting carbonyl carbon. In addition, the slow-reacting enantiomer, (S)-4-bromomethyl-β-lactone, encounters steric hindrance between the bromo substituent and the side chain of the Leu278 residue, while the fast-reacting enantiomer does not have any steric clash. Copyright
Efficient synthesis of a chiral precursor for angiotensin-converting enzyme (ace) inhibitors in high space-time yield by a new reductase without external cofactors
Shen, Nai-Dong,Ni, Yan,Ma, Hong-Min,Wang, Li-Juan,Li, Chun-Xiu,Zheng, Gao-Wei,Zhang, Jie,Xu, Jian-He
supporting information; experimental part, p. 1982 - 1985 (2012/06/01)
A new reductase, CgKR2, with the ability to reduce ethyl 2-oxo-4-phenylbutyrate (OPBE) to ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-HPBE), an important chiral precursor for angiotensin-converting enzyme (ACE) inhibitors, was discovered. For the first time, (R)-HPBE with >99% ee was produced via bioreduction of OPBE at 1 M without external addition of cofactors. The space-time yield (700 g·L-1·d -1) was 27 times higher than the highest record.
Stereospecific reduction of methyl o-chlorobenzoylformate at 300 g·L-1 without additional cofactor using a carbonyl reductase mined from Candida glabrata
Ma, Hongmin,Yang, Linlin,Ni, Yan,Zhang, Jie,Li, Chun-Xiu,Zheng, Gao-Wei,Yang, Huaiyu,Xu, Jian-He
experimental part, p. 1765 - 1772 (2012/08/08)
In order to search for oxidoreductases suitable for the preparation of methyl (R)-o-chloromandelate [(R)-CMM], the key intermediate for clopidogrel, the homologous proteins of Gre2p were expressed in Escherichia coli, among which CgKR1 showed the most satisfactory activity and stereoselectivity towards methyl o-chlorobenzoylformate (CBFM). Using the crude enzyme of CgKR1 and glucose dehydrogenase (GDH), as much as 300 g·L-1 of CBFM was almost stoichiometrically converted to (R)-CMM with excellent enantiomeric excess (98.7% ee). More importantly, the reaction could be performed without external addition of an expensive cofactor. The substrate profile indicates that keto esters serve as the most suitable substrate, which was confirmed by gram-scale preparations. Homology modeling and docking analysis revealed the molecular basis for the high stereoselectivity of CgKR1. These demonstrate not only the feasibility of in silico mining of novel enzymes based on sequence homology but also the applicability of this new reductase for the practical production of optically active (R)-CMM. Copyright
Efficient reduction of ethyl 2-oxo-4-phenylbutyrate at 620 ?l -1 by a bacterial reductase with broad substrate spectrum
Ni, Yan,Li, Chun-Xiu,Zhang, Jie,Shen, Nai-Dong,Bornscheuer, Uwe T.,Xu, Jian-He
supporting information; experimental part, p. 1213 - 1217 (2011/07/09)
A β-ketoacyl-ACP reductase (FabG) gene from Bacillus sp. ECU0013 was heterologously overexpressed in Escherichia coli and the encoded protein was purified to homogeneity. The recombinant reductase could reduce a broad spectrum of prochiral ketones including aromatic ketones and keto esters and showed the highest activity in the asymmetric reduction of ethyl 2-oxo-4-phenylbutyrate (OPBE). Using E. coli cells coexpressing both FabG and glucose dehydrogenase (GDH) genes, as much as 620 ?L-1 of OPBE was almost stoichiometrically converted to ethyl (S)-2-hydroxy-4-phenylbutyrate [(S)-HPBE] with excellent (>99%) enantiomeric excess. More importantly, the process could be performed smoothly without external addition of an expensive cofactor as usually done and could be scaled up very easily. All these positive features demonstrate the applicability of this reductase for the large-scale production of optically active α-hydroxy acids/esters.
Highly stereoselective reduction of prochiral ketones by a bacterial reductase coupled with cofactor regeneration
Ni, Yan,Li, Chun-Xiu,Wang, Li-Juan,Zhang, Jie,Xu, Jian-He
experimental part, p. 5463 - 5468 (2011/09/12)
A carbonyl reductase gene (yueD) from Bacillus sp. ECU0013 was heterologously overexpressed in Escherichia coli, and the encoded protein (BYueD) was purified to homogeneity and characterized. The NADPH-dependent reductase showed a broad substrate spectrum towards different aromatic ketones, and α- and β-ketoesters. Although the enantioselectivity was high to moderate for the reduction of α-ketoesters, all the tested β-ketoesters and aromatic ketones were reduced to the corresponding chiral alcohols in enantiomerically pure forms. Furthermore, the practical applicability of this enzyme was evaluated for the reduction of ethyl 4-chloro-3-oxobutanoate (1a). Using Escherichia coli cells coexpressing BYueD and glucose dehydrogenase, 215 g L-1 (1.3 M) of 1a was stoichiometrically converted to ethyl (R)-4-chloro-3-hydroxybutanoate ((R)-1b) in an aqueous-toluene biphasic system by using a substrate fed-batch strategy, resulting in an overall hydroxyl product yield of 91.7% with enantiomeric purity of 99.6% ee.
Asymmetric reduction of substituted α- and β-ketoesters by Bacillus pumilus Phe-C3
He, Chunmao,Chang, Dongliang,Zhang, Jie
, p. 1347 - 1351 (2008/12/20)
The enantioselective reduction of substituted α- and β-ketoesters using resting cells of Bacillus pumilus Phe-C3 was investigated. Effects of substrate concentration on the catalytic efficiency of the microorganism were studied. Preparative scale productions were carried out under the optimized conditions with 62.4-91.0% yields and 90.2-97.1% ee. The cells retained 80% of initial activity after recycling for six times.
