95537-36-3Relevant articles and documents
Synthesis method of quaternary amine inner salt
-
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.
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