CROSS-LINKED CRYSTALS OF CANDIDA-RUGOSA LIPASE - HIGHLY EFFICIENT CATALYSTS FOR THE RESOLUTION OF CHIRAL ESTERS

To date, most enzyme-based organic syntheses have employed enzymes in the form. of a crude protein extract. The instability and expense of h ighly purified proteins has all but obviated their use as catalysts fo r enantioselective hydrolyses. Herein, we describe the use of the majo r hydrolase from commercial Candida rugosa lipase (CRL) in the form of a cross-linked enzyme crystal (CLEC) for the enantioselective hydroly sis of chiral racemic esters. The enantioselectivity of CRL-CLECs in t he hydrolysis of many important chiral esters is vastly superior to th at of the crude CRL extract. Since the CRL-CLEC is insoluble, recovera ble, and 2-3 orders of magnitude more stable than the soluble protein, the CRL-CLEC is an attractive replacement for the crude enzyme prepar ation. The use of this catalyst in the resolution of chiral esters 1-1 1 and in the preparative scale (la):and multicycle resolution (2a) of important anti-inflammatory drugs is described.