Research On The Resolution Of Antiinflammatory Drugs 2-Arylpropionic Acids By Enzyme

Ibuprofen, (R,S) 2 (4 isobutyl phenyl) propionic acid, is an importantnon steroidal anti inflammatory drugs which belongs to the family of2 arylpropionic acid derivatives. It’s significant pharmacological activityoften denpend on the chirality of these compounds. Studies have shownthat the S (+) enantiomer is known to be about 100 times more active thanits R ( ) enantiomer, and (R) ibuprofen potentially have side effects. Inorder to reduce complications and correct evaluation of drug, racemicibuprofen resolution is particularly important and has become a researchhotspot. A resolution of racemic ibuprofen which reported in literatures hasbeen achieved by enzyme catalyzed or microbe cells enantioselectivehydrolysis of the corresponding racemic esters, amides and nitriles,esterification and so on.Enzyme catalyzed organic reactions possess many advantages, such asmild reaction conditions, friendly environments, quick rate and highselectivity. But the traditional organic solvents restrict enzyme activity andstability. Over the years, many groups attempted to solve the problems of enzyme immobility and deactivation in organic solvents. Recently, usingionic liquids replace of organic solvents as enzyme catalyzed reactionmedium has been a novel field. Meanwhile coating an enzyme withsurfactants or lipids to make it soluble and active in organic solvents is alsobecome a novel technique in recent 10 years.In this paper, the lipase from Candida cylindrucea catalyzedenantioselective hydrolysis of racemic ibuprofen ester reaction system wasstudied, a series of researches were carried out:Firstly, the natural free enzyme catalyzed enantioselective hydrolysisracemic ibuprofen reaction in water saturated ionic liquid has been studied.Results showed that [BMIM][BF4] ionic liquid can be used as solvent inthe enzyme catalysis reaction. As compared with free lipase enzyme, thelipase in microemulsion based gels on the hydrolysis reaction in ionicliquid is also explored, the activity and enantioselectivity has beenimproved.Secondly, glutamic acid dialkyl ester were synthesized and used tocoat the lipase from Candida cylindrucea. The lipid coated lipase as acatalyst in N, N dimethylformamide (DMF) solvents was investigated inenantioselective hydrolysis of racemic ibuprofen methyl ester. Variousfactors of the reaction were evaluated and identified the optimum reactionconditions. Through kinetic parameters research, the hydrolysis reactionfollows the Michaelis Menten equation. Results showed that through the lipid coating lipase in organic solvent system has a higher catalytic activityand the enantioselectivity.