卡巴他赛关键中间体7β,10β-二甲氧基-10-脱乙酰巴卡汀Ⅲ的合成新方法

摘要

OBJECTIVE: To synthesize key intermediate of cabazitaxel, i.e. 7β, 10β-dimethoxy-10-deacetoxybaccatin III with a new method. METHODS: At first, the C(7) and C(10) hydroxy of 10-deacetoxybaccatin III selectively protected; and then, the C(13) hydroxyl was protected by an another reagent. After the deprotection of C(7) and C(10) aydroxyl, the methyla-tion was carried on C(7) and C(10). 7β, 10β-dimethoxy- 10-deacetoxybaccatin Iff was obtained after the deprotection of C(13) hydroxyl, which was characterized by 1H-NMR. RESULTS: 7β, 10β-dimethoxy- 10-deacetoxybaccatin Iff was synthesized successfully with 5 steps of reactions, with purity of 95% and yield of 97%. CONCLUSION: The method will benefit from the good yield, mild conditions and convenient operations, which is suitable for industrial production.%目的:以新方法合成抗癌药卡巴他赛关键中间体节,10β-二-甲氧基-10-脱乙酰巴卡汀Ⅲ.方法:以10-脱乙酰基巴卡汀Ⅲ为原料,选择性在7位、10位羟基引入保护基后,在13位羟基引入不同保护基,然后选择性脱去7位、10位羟基上的保护基,接着在7位、10位羟基上甲基化,后脱去13位保护基,从而得到7β,10β--二甲氧基-10-脱乙酰巴卡汀Ⅲ；经1H-NMR对目标化合物进行验证.结果:经过5步反应合成了7β,10β-二甲氧基-10-脱乙酰巴卡汀Ⅲ,纯度为95％,收率为97％,经验证确定为目标化合物.结论:该合成方法条件温和、操作方便、收率较高,适合大规模生产.