Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Via Saldini 50, 20133 Milano, Italy.
Chemical-Pharmaceutical Consulting and IP Management, Viale Giovanni da Cermenate 58, 20141 Milano, Italy.
Molecules. 2018 Aug 31;23(9):2206. doi: 10.3390/molecules23092206.
Brivaracetam is a new anticonvulsant compound, recently approved as an antiepileptic drug. This drug substance presents a 4-substituted pyrrolidone structure: the (4)-configuration of the stereocenter present on the heterocyclic ring is the main target of the synthesis. The described method allows to prepare the suitable optically pure 2-substituted primary alcohol by means of a lipase-catalyzed transesterification. The obtained (2)-alcohol was easily transformed into the (3)-3-propylbutyrolactone, an advanced intermediate of brivaracetam. The described synthetic pathway is completed with the chromatographic methods and the NMR analyses necessary to establish the chemical and the optical purity of the intermediates and of the final lactone.
布瓦西坦是一种新型抗惊厥化合物，最近被批准为抗癫痫药物。这种药物的主体结构是 4-取代的吡咯烷酮：杂环上的手性中心的（4）-构型是合成的主要目标。所描述的方法允许通过脂肪酶催化的酯交换反应制备合适的光学纯 2-取代的仲醇。获得的（2）-醇很容易转化为（3）-3-丙基丁酸内酯，这是布瓦西坦的一个高级中间体。所描述的合成途径通过色谱方法和 NMR 分析完成，这些方法是确定中间体和最终内酯的化学和光学纯度所必需的。
