R-stereopreference analysis of lipase Novozym 435 in kinetic resolution of flurbiprofen.
Immobilized lipase from Candida antarctica (Novozym 435) was employed in the kinetic resolution of racemic flurbiprofen by enantioselective esterification with methanol. It was found that the lipase has the R-stereopreference and the reaction matches Bi Bi Ping Pong mechanism with dead-end inhibition of methanol. Furthermore, the R-stereopreference was analyzed in details from the aspects of enzymatic kinetic mechanism and reaction activation energy of both enantiomers. The R-enantiomer shows lower activation energy and higher maximum reaction rate than the S-enantiomer, which implies the R-stereopreference of the lipase and makes the kinetic resolution of flurbiprofen via enzymatic reaction feasible.
Zhang
Hua Yun
HY
Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117576.
Wang
Xin
X
Ching
Chi Bun
CB
D002175:Candida / Q000201:enzymology; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004800:Enzymes, Immobilized / Q000737:chemistry; D004951:Esterification; D005480:Flurbiprofen / Q000737:chemistry*; D005656:Fungal Proteins; D007700:Kinetics; D008049:Lipase / Q000737:chemistry*; D000432:Methanol / Q000737:chemistry; D008956:Models, Chemical; D015233:Models, Statistical; D008962:Models, Theoretical; D013237:Stereoisomerism; D013696:Temperature
D002257:Carbonic Anhydrase Inhibitors; D004800:Enzymes, Immobilized; D005656:Fungal Proteins; D005480:Flurbiprofen; C093667:Novozyme 435; D008049:Lipase; D000432:Methanol