Candida rugosa lipase-catalyzed production of optically pure S-(+)-ketoprofen = Candida rugosa 리파제를 이용한 광학적으로 순수한 S-(+)-Ketoprofen의 생산

Abstract

Enzymatic resolution reactions were investigated using Candida rugosa lipase for the production of potically pure S-(+)-Ketoprofen. When the enzymatic hydroysis (and esterification) of recemic ketoprofen esters (and recemic ketoprofen with alcohol) was investigated comparatively, aqueous media was more specific for S-enantiomer than organic media. In the enzymatic hydrolysis of racemic ketoprofen ethyl ester in aqueous media, optimal temperature and pH for enantioselectivity were 37℃ and 4, respectively. The stereoselectivity of the enzyme was enhanced by adding dialcohols such as ethylene glycol and propylene glycol. The enantiomeric ratio obtained in the 40 %(v/v) ethylene glycol was 2-fold higher than that without the additive. By adding CH2CI2, CHCI3 and CCI4 (5%,v/v), the enantioselectivity was reversed. A dramatic increase in the stereoselectivity was achieved using lipase purified by anion exchange chromatography. The type A lipase(the first eluted lipase fraction) showed an enantiomeric ratio of >100, whereas the type B lipase(the second eluted lipase fraction) exhibited enantimomer ratio of 9.0 in the hydrolysis of racemic ketoprofen ethyl ester