抗帕金森新药雷莎吉兰的手性合成

Asymmetric synthesis of rasagiline

目的:探索雷莎吉兰不对称合成的新方法。方法:以1-茚酮为原料,经"一锅法"与R-叔丁基亚磺酰胺生成亚胺,后用NaBH4还原,经柱分离得到胺,再酸水解除去保护基得到R-1-氨基茚,再与丙炔氯结合,甲磺酸成盐得到雷莎吉兰。结果:经检测,所合成雷莎吉兰的旋光值,质谱,氢谱数据均与文献符合。结论:用手性的叔丁基亚磺酰胺合成手性胺是一种行之有效的方法,可运用在雷莎吉兰的合成中。

Objective：To build the method of asymmetric synthesis of Rasagiline. Methods：（R）-tert-butanesu-lfinamide and 1-indanone were used as the starting material. The resulted imines were reduced with NaBH4 in THF to provide the corresponding secondary sulfinamides in high yield and diastereoselectivity. By series of reactions, rasagiline was synthesized. Results： The chemical structure of the target compound was confirmed by the melting point, NMR, MS and optical activity. Conclusion：By using （R）-tert-butanesulfinamide, rasagiline can be synthesized with high yield and good asymmetric selectivity.