A novel lipase from Aspergillus oryzae WZ007 catalyzed synthesis of brivaracetam intermediate and its enzymatic characterization

Abstract Brivaracetam is a structural derivative of the chiral drug levetiracetam and has been approved for the adjuvant treatment of partial epilepsy. As a new antiepileptic drug, it is widely used in a variety of epilepsy models. In this study, a novel lipase M16 derived from Aspergillus oryzae WZ007 was cloned, expressed, and used for chiral resolution. Lipase M16 has a high enantioselectivity to the racemic substrate ( R , S )‐methyl 2‐propylsuccinate 4‐ tert ‐butyl ester, and the intermediate ( R )‐2‐propylsuccinic acid 4‐ tert ‐butyl ester of brivaracetam was obtained efficiently. Under optimal conditions, the enantiomeric excess of substrate was up to 99.26%, and the e.e . p was 96.23%. The conversion and apparent E value were 50.63% and 342.48, respectively. This study suggests a new biocatalytic resolution via lipase M16 for preparing the brivaracetam chiral intermediate and its potential application in the pharmaceutical industry.