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.

Resolution of N‐acetyl‐DL‐methionine methyl ester by the lipase from Brucella thiophenivorans

“…Novozym 435 (lipase B from Candida antarctica immobilized on macroporous polyacrylate resin), Lipozyme TL IM (lipase from Thermomyces lanuginosus immobilized on silica), and Lipozyme RM IM (lipase from Rhizomucor miehei immobilized on ionic resin) were purchased from Novozymes A/S (Bagsvaerd, Denmark). Thermomyces dupontii lipase TDL2, 13 Aspergillus oryzae lipase M16, 14,15 AOL, 16 and AOL-3 17 were previously described and obtained accordingly. Lipase L1 (GenBank no.…”

Chemical modification of lipases: A powerful tool for activity improvement

“…Lima et al [25] used two different lipases, differing in selectivity, for the synthesis of Pindolol, a nonselective β-blocker. Firstly, lipase from Lipase from Candida antarctica B Crizotinib [22] Immobilized lipase from Candida antarctica B Buprenorphine [23] Lipase from Thermomyces lanuginosus and immobilized lipase from Candida antarctica B Methotrexate [24] Lipases from Pseudomonas fluorescens and Candida rugosa Pindolol [25] Lipase from Candida rugosa Propranolol [26] Lipase from Aspergillus oryzae (WZ007) Brivaracetam [27] Lipase from Candida antarctica B Practolol, Pindolol, and Carteolol [28] Pseudomonas fluorescens was applied on the kinetic resolution of one drug intermediate, followed by the hydrolysis of the other intermediate by a lipase from Candida rugosa. The final drug was isolated in quantitative yield with an excellent enantiomeric excess (ee 97%).…”