Enzymatic resolution of (S)-(+)-Naproxen in a trapped aqueous-organic solvent biphase continuous reactor

A trapped aqueous-organic biphase system for the continuous production of ( S)-(+)-2-(6-methoxy-2-naphthyl) propionic acid (Naproxen) has been develope d. The process consists of a stereoselective hydrolysis of the racemic Napr oxen methyl ester by Candida rugosa lipase in a trapped aqueous-organic bip hase system. The reaction has been carried our in a laboratory-scale contin uous-flow stirred tank reactor (CSTR). The staring material has been suppli ed in and remaining substrate recovered by organic phase. YWG-C6H5, a poorl y polar synthetic support, has been employed to immobilize the lipase and t o restrict the aqueous phase. Lipase immobilized on YWG-C6H5 containing aqu eous phase has been added into the CSTR to catalyze the hydrolysis. A dialy sis membrane tube containing a continuous flow closed-loop buffer has been applied in the CSTR for the extraction of product and recruiting of the aqu eous part consumed. Various reaction conditions have been studied. The acti vity of immobilized enzyme was effected by the polarity of support, the sub strate concentration, logP value of organic phase and the product inhibitio n. At steady-state operating conditions, an initial conversion of 35% has b een obtained. The CSTR was allowed to operate continuously for 60 days at 3 0 degrees C with a 30% loss of activity. The hydrolysis reaction yielded (S )-(+)-Naproxen with >90% enantiomeric excess and overall conversion of 30%. (C) 2000 John Wiley & Sons, Inc.