Fed-batch production of ( S)-flurbiprofen in lipase-catalyzed dispersed aqueous phase reaction system induced by succinyl β-cyclodextrin and its extractive purification

Abstract

Optically active ( S)-flurbiprofen was produced fed-batch-wisely in a lipase-catalyzed dispersed aqueous phase reaction system induced by succinyl β-cyclodextrin (suβ-CD). A highly concentrated 480 mM ( S)-flurbiprofen, corresponding to 117.0 g/l, with an enantiomeric excess of 0.98 and conversion yield of 0.48 was obtained. ( S)-Flurbiprofen produced in an inclusion complex form with suβ-CD was extractively purified using three-step procedures: decomplexation of ( S)-flurbiprofen and residual ( R)-flurbiprofen ethyl ester (( R)-FEE) using the ethyl acetate, dissolution of ( S)-flurbiprofen from ( R)-FEE using a sodium bicarbonate solution, and selective precipitation of ( S)-flurbiprofen using 2-propanol. Consequently, an extremely high concentration of 420 mM ( S)-flurbiprofen with an optical purity higher than 98% was recovered after purification.