手性药物噻吗洛尔的合成研究

Research of the Synthesis of Chiral Drug S-(-)-Timolol

目的研究一种实用的适合于工业生产的全合成方法。方法我们从手性合成子D-型甘露醇开始制备S-型噻吗洛尔。S-型3-特丁基-1,2-丙二醇与苯甲醛生成唑烷类衍生物,唑烷类衍生物与3-氯-4-吗啡基-1,2,5-噻二唑在叔丁醇钾的叔丁醇溶液中缩和,然后水解,最终给出目的产物S-型噻吗洛尔。结果在分析和尝试文献提供的合成方法基础上,探索确定了本全合成路线。结论我们使每一步的合成都得到了优化,从而降低了成本和简化了操作过程,该工艺未见国内报道。

Objective Study a practical total- synthetic method that is suitable to industrialization. Meth. ods The S - （ - ） - timolol is prepared from a chiral synthon D - mannitol. The treatment of S- （ - ） - 3 - t - butylamino- 1,2- propanediol with benzaldehyde afforded the oxazolidine derivative. S（ - ） - tornolol could be obtained from oxazolidine derivative by treatment with 3 - chloro - 4 - morpholino - 1,2,5 - thiadiazole and t - BuOK in t - BuOH and hydrolization. At last give the target product. S- （ - ） - timolol. Results The synthetic route is determined and investigated after the analyzing and trying for the literal synthetic methods. Conclusion The synthetic technology of each step has been optimized, resulting in decreasing the cost and simplifying the operation procedures.