Research Synthesis Of Antiepileptic Drug Levetiracetam

This paper presents the efficacy of new and traditional antiepileptic drugs and the principle of rational choice antiepileptic drugs, based on the existing literature. Hereby, the mechanism of action, pharmacokinetics, clinical application and safety of levetiracetam were described comprehensively.Levetiracetam has a unique mechanism of action and has good efficacy and safety, it can be used as adjuvant therapy for refractory epilepsy, also be used for treatment for newly diagnosed epilepsy alone, it has broad application prospects in antiepileptic area.According to preparation literature from domestic and foreign about levetiracetam, we have conducted study for three synthesis routes of levetiracetam. Its structure is elucidated by NMR, IR, Elemental analysis, Mass spectrometry and Liquid chromatography.The first route use L-methionine as starting marterial and obtain levetiracetam by esterification, ammonolysis, cyclization and removal methylthio reaction. The total yield is 38.4%. But active nickel was used in manufacturing process, it would be potential safety hazard during preparation, application and storage of active nickel.The second route define (S)-2-aminoburyric acid as starting material and obtain levetiracetam by esterification, cyclization and ammonolysis. But the side product is easily produced in the last ammonnolysis reaction.The starting material of (S)-2-aminobutanamide as chiral rource was used in the third route, the levetiracetam was obtained by esterification and ammonolysis and then cyclization, the total yield is 49.3%. During the third route, the reaction conditions was opitimized and the critical parameters was defined. The D-isomer of levetiracetam was controlled.The third route has the advantages of mild reaction conditions, it does not need to separate enantiomers and not need special raw material and equipment, fewer side effects and higher quality of product. This route is suitable for industrial production.