Kinetic Modeling and Statistical Optimization of Lipase Catalyzed Enantioselective Resolution of (R,S)-2-pentanol

Abstract

S-2-pentanol is a chiral intermediate in the synthesis of several potential antialzheimer's drugs that inhibit β-amyloid peptide release or its synthesis. The present work focuses on the kinetic resolution of (R,S)-2-pentanol using vinyl acetate as an acyl donor. Effects of various parameters were studied to deduce the kinetics and mechanism of the reaction. Novozyme 435 was found to be the most efficient catalyst among different catalysts studied. Response Surface methodology and BoxÀBehnken design were employed to evaluate the effect of process parameters such as speed of agitation, enzyme loading, temperature and acyl donor/ alcohol molar ratio on conversion, enantiomeric excess, enantioselectivity and initial rate. Initial rate data and progress curve data were used to arrive at a suitable model. PingÀpong biÀbi mechanism with 2-pentanol inhibition was found to describe the kinetics of the reaction. The kinetic parameters evaluated from initial rate data were used to simulate the experimental results. There was a very good agreement between theory and experiment.

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

“…Design Expert software can be used to obtain each response, and response surface plots were obtained after analysis of each response. After each response had been analyzed, multiple response optimizations were done by numerical tools provided by Design Expert (version 8.0.6) …”

“…Therefore, β ‐cyclodextrin derivatives were added into the aqueous solution to increase the solubility of the ( + , ‐ )‐2‐(4‐MP)PPAME and to accelerate the rate of hydrolysis reaction without affecting the stereoselectivity and activity of the enzyme. The factors influencing the lipase‐catalyzed hydrolysis process were studied and response surface methodology (RSM) was used to optimize the reaction system …”

Towards a green enantiomeric esterification of R/S-ketoprofen: A theoretical and experimental investigation

“…Lipases are one of the most suitable enzymes for kinetic resolution of profens due to their wide substrate specificity, their ability to recognize chirality and do not require labile cofactors [12]. Moreover, from an environmental point of view, processes that use enzymes are greener, less hazardous and friendlier because they do not contaminate as in the case of using chemical catalysts [13,14].…”

Immobilized lipase catalyzed synthesis of n‐amyl acetate: parameter optimization, heterogeneous kinetics, continuous flow operation and reactor modeling

“…The conventional method for optimization of process parameters involves changing one variable at a time, while keeping others at fixed levels. [39][40][41][42][43][44] Commercial technologies based on immobilized enzymes are based on batch operations in stirred tank reactors. These investigations can clarify the effect of individual variables on the desired output such as conversion and selectivity, but may not really account for the interactive effects between the variables.…”