Lipase‐catalyzed hydrolysis of (+,‐)‐2‐(4‐methylphenyl) propionic methyl ester enhanced by hydroxypropyl‐β‐cyclodextrin

Abstract

BACKGROUND Enzymatic kinetic resolution is an attractive technology for production of enantiomerically pure compounds. The objective of this research is to investigate the enantioselective hydrolysis of (+,‐)‐2‐(4‐methylphenyl) propionic methyl ester (2‐(4‐MP)PPAME) to (+)‐2‐(4‐methylphenyl) propionic acid ((+)‐2‐(4‐MP)PPA) catalyzed by enzyme in an aqueous medium. RESULTS Lipase AY from candida rugosa (CRL) was screened as the best lipase. Novozym 435 IM and lipopan S BG show higher catalytic activity but the enantioselectivity is very low. By addition of hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) to the aqueous system, an increased substrate conversion of 45.28% was obtained, the high enantiomeric excess remaining compared with the conversion of 28.05% without HP‐β‐CD. Response surface methodology and central composite design were employed to model and optimize the reaction system. CONCLUSION Under the optimal conditions including pH of 6.60, 12.5 mg mL−1 enzyme, 35 mmol L−1 HP‐β‐CD, 0.06 mmol substrate, temperature 39°C, agitation speed 400 rpm and 40 h reaction time, the substrate conversion was up to 40.32% and the optical purity of the product (+)‐2‐(4‐methylphenyl) propionic acid was up to 95.22%. © 2018 Society of Chemical Industry

Simulation and optimization of Novozym 40086 kinetic resolution of α‐cyclopentylphenylacetic acid enantiomers

“…The dissociation states of the active group are broken when the pH is higher or lower than the optimum pH, which reduces the binding between enzyme and substrate, and thus the catalytic performance of Novozym 40086 decreases. This phenomenon is consistent with the reported literature that the enzyme exhibits the highest activity and enantioselectivity under optimal pH . Thus, pH 6.5 was considered to be the optimal pH for the resolution reaction, when the highest ee p and c S values of 96.38% and 54.25%, respectively, were achieved.…”

“…Novozym 40086 is a commercially available lipase derived from Rhizomucor miehei immobilized on acrylic resin beads, which has been applied for kinetic resolution and other fine chemical processes . Many scholars have reported that chiral drugs are resolved by enzymatic hydrolysis of the corresponding racemic esters in aqueous phase . However, it is very common that the reaction has low conversion because of the poor solubility of substrates in the aqueous systems .…”

Lipase-Catalyzed Production of (S)-Carprofen Enhanced by Hydroxyethyl-β-cyclodextrins: Experiment and Optimization

“…The solubility of ( R , S )-CPOMe in aqueous solution is very poor. Low solubility of ester will result in low total conversion in the enzymatic hydrolysis reaction system. , Adding the additives into aqueous phase can improve the solubility of substrate and the hydrolysis reaction rate. , …”

“…7 Racemic resolution is simple, easy to use for industrial production, low cost, and has a short short development time. 8 Therefore, it has been dominant in industrial applications. In general, racemic separation techniques include crystallization, 9 simulated moving bed chromatography (SMB), 10 membrane, 11 enantioselective liquid− liquid extraction (ELLE), 12−14 and so on.…”

“…Chemical synthesis is effective for obtaining a single enantiomer, but the development of this method would be time-consuming and expensive . Racemic resolution is simple, easy to use for industrial production, low cost, and has a short short development time . Therefore, it has been dominant in industrial applications.…”