Title : Insight into microwave assisted enzyme catalysis in process intensification of reaction and selectivity: Kinetic resolution of (R,S)-flurbiprofen with alcohols - Gupta_2017_Mol.Catal_440_50 |
Author(s) : Gupta SM , Kamble MP , Yadav GD |
Ref : Molecular Catalysis , 440 :50 , 2017 |
Abstract :
Biocatalysis has potential applications in pharmaceuticals, fine chemicals and drug industries for the synthesis and separation of chiral compounds. The current work deals with the kinetic resolution of (R,S)-flurbiprofen using immobilized Candida antarctica lipase B under the influence of microwave irradiation. Flurbiprofen (R,S)-[2-(3-fluro-4-phenyl) phenyl] propionic acid is one of the most widely used non-steroidal anti-inflammatory drugs (NSAID). It exists in two enantiomeric forms as (R,S)-flurbiprofen because it has a single stereogenic center. Pharmacological action of flurbiprofen resides with the S form by inhibiting Cox-2 activity and results in anti-inflammatory action and hence (R)-flurbiprofen causes gastrointestinal infection. Novozym 435 was found to be most active among others for the stereoselective esterification of the R-enantiomer in organic reaction media. Microwave irradiation shows a synergistic effect on enzyme catalysis by enhancing both rate of the reaction and conversion of R-enantiomer into an ester. Effects of various reaction parameters such as solvent, speed of agitation, mole ratio, type of alcohol, temperature, catalyst loading, and reusability were studied. Maximum conversion of R-flurbiprofen ester under microwave irradiation was found to be -44.4% with enantioselectivity (E) of 478, eeP=98.9% and eeS=79.07% in 6h, whereas in conventional heating the maximum conversion was 17% with enantioselectivity (E) of 126, and eeS=20.12% in 6h. The ping-pong bi-bi mechanism with inhibition by methanol was proposed for the kinetic resolution of (R,S)-flurbiprofen and validated against experimental data. |
PubMedSearch : Gupta_2017_Mol.Catal_440_50 |
PubMedID: |
Gupta SM, Kamble MP, Yadav GD (2017)
Insight into microwave assisted enzyme catalysis in process intensification of reaction and selectivity: Kinetic resolution of (R,S)-flurbiprofen with alcohols
Molecular Catalysis
440 :50
Gupta SM, Kamble MP, Yadav GD (2017)
Molecular Catalysis
440 :50