Enantioselective desymmetrization of prochiral diesters catalyzed by immobilized Rhizopus oryzae lipase

Abstract

The asymmetric hydrolysis of dimethyl 3-phenylglutarate 1 catalyzed by different immobilized preparations of Rhizopus oryzae lipase (ROL) has been studied. The Lewatit CNP 105 commercial support was activated to aldehyde groups (Lewatit-aldehyde) and used as a support for the immobilization of ROL using different strategies. Thus, the lipase immobilized in the presence of dithiothreitol at pH 7 (ROL-Lew-pH 7) was the most enantioselective catalyst for the hydrolysis of 1 at pH 7 and 25°C producing the (R)-monoester with an E value of 4.2 (ee=62%) whereas ROL immobilized at pH 10 gave only an E value of 1.1 (ee=4%). The medium engineering was also an interesting tool for improving the lipase selectivity. The addition of a solvent, combined with decreasing temperature improved the E value for the reaction from 4.2 to 24 (ee=62 to ee=92%). Finally, the application of the ROL-Lew-pH 7 preparation in the presence of 20% dioxane and 5°C allowed us to obtain the (R)-isomer of the monoester with an E value of 24 (ee=92%) in a 97% yield (of monoesters).