Lipase Catalyzed Naproxen Methyl Ester Enantioselective Hydrolysis in Ionic Liquids

A series of dialkylimidazolium ionic liquids with various anions including hexafluorophosphate alkane sulfonate and tetrafluoroborates were studied in the lipase-catalyzed enantioselective hydrolysis. Lipase activity,stability and enantioselectivity were determined by both of alkane and anions. In the best aqueousC4mimPF6 biphasic system lipase resolution of Naproxen proceed with much effective. It was observed that the activity of lipase in aqueousC4mimPF6 system was comparable with that in aqueous-organic system, but the enantiomeric ratio of Lipase-catalysis hydrolysis in aqueous C4mimPF6 biphasic system (E>300) was much higher than that in aqueous -organic biphasic system (E≈90). Introduction (S)-(+)-2-(6-Methoxy-2-naphtyl) propionic acid (Naproxen) is a non-steroidal anti-inflammatrory drug and the physiological activity of the S-Naproxen is 28-fold higher than that of R-form[1] .The methods for product S-Naproxen has been intensively explored and enzymatic resolution of Naproxen is efficient and can be performed by hydrolysis[2,3] and esterification[4,5]. As the two methods from the standpoint of high productivity, easy product separation, and few reaction steps, lipase-catalyzed asymmetric hydrolysis has been judged to be superior for the practical resolution of racemic acids [6]. Anterior studies of asymmetric hydrolysis often carry through in aqueous system or in aqueous-organic biphasic system. In the first system the relatively low solubility of substrate cause a low reaction rate [7]. In the second system the substrate can be dissolved in an organic phase, while the emulsion made difficult to separate the product and substrate, decreased the stability of the enzyme, the volatile organic is dangerous and it does not accord with the” Green chemistry” tenet [8]. To overcome the aforementioned problems, room-temperature ionic liquids are an appreciate choice. Ionic liquids have been reported as non-volatile, non-flammable, low toxicity, and good solubility for many organic and inorganic materials. They also be reported can enhance activity, selectivity and stability of catalysts in chemical reactions [9, 10], and can dramatically reduce the use of hazardous and volatile polluting organic solvents.

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