左乙拉西坦及其衍生物的合成

Synthesis of levetiracetam and its derivatives

目的:探讨左乙拉西坦及其衍生物的制备方法。方法:以2-吡咯烷酮为起始原料,经成盐和取代得外消旋中间体(±)-α-乙基-(2-氧-1-吡咯烷基)乙酸(1),再以R-α-苯乙胺为拆分剂,得中间体(S)-α-乙基-(2-氧-1-吡咯烷基)乙酸(3),3分别与相应的氨、胺或醇发生酰化反应,得到左乙拉西坦及其衍生物。结果:得到左乙拉西坦及其9个衍生物,8个作者未见文献报道。经红外光谱1、HNMR或元素分析认定结构正确。结论:本合成工艺有助于工业化生产,9个目标化合物对提高药物促智作用,降低不良反应能起到积极作用。

Objective： To investigate synthesis of levetiracetan and its derivatives. Methods： The racemic（ ＋ ）-α-ethyl-（2-oxo-1-pyrrolidinyl）acetic acid （1） was obtained via the salt forming and substitution of 2-pyrrolidone. The intermediate （S） -α-ethyl-（2-oxo-1-pyrrolidinyl） acetic acid （ 3 ） was obtained from the racemic 1 by chemical resolution with an optically active （R）-α-methyl-benzylamine. The intermediate 3 was treated with corresponding amine or alcohol to provide levetiracetan and its 9 analogs. Results： Levetiracetan and its 9 derivatives, where 8 were new compounds, were obtained, and their structures were confirmed by IR. ^1HNMR or elemental analyses. Conclusion ： The preparation method of levetiracetam is good to its industrialization and the 9 analogs are useful for searching more effective lead compound.