Lipase-catalyzed production of optically active ( S)-flurbiprofen in aqueous phase reaction system containing chiral succinyl β-cyclodextrin

Abstract

The lipase-catalyzed production of optically active ( S)-flurbiprofen was carried out in a dispersion reaction-system induced by chiral succinyl β-cyclodextrin (suβ-CD). The optimal reaction conditions were 500 mM ( R, S)-flurbiprofen ethyl ester (( R, S)-FEE), 600 units of Candida rugosa lipase per 1 mmol of ( R, S)-FEE, and 1000 mM suβ-CD at 37 °C for 72 h. An extremely high enantiomeric excess of 0.98 and conversion yield of 0.48 were achieved in the dispersed aqueous phase reaction system containing chiral suβ-CD added as a dispenser and chiral selector. The inclusion complex formability of the immiscible substrate ( S)- and ( R)-form of FEE with suβ-CD was compared using a phase-solubility diagram, DSC, and 1H NMR. ( S)-Isomer formed a more stable and selective inclusion complex with chiral suβ-CD. It was hydrolyzed much more selectively by lipase from C. rugosa, due to the selective structural modification through inclusion complexation with chiral suβ-CD.