新型紫杉烷类抗肿瘤药物卡巴他赛的合成研究

目的改进抗肿瘤药物卡巴他赛的合成方法。方法以10-去乙酰基巴卡亭Ⅲ(10-DABⅢ)为起始原料,经过双甲醚化、酯化偶联、脱保护3步反应制得目标产物。结果与结论采用不同保护基的C-13侧链对酯化偶联反应具有重要的影响;确定了一条实用的制备卡巴他赛的合成路线,3步反应总收率达到41.7%(以10-DABⅢ计)。目标产物的结构经1H-NMR和MS谱确证。该合成路线适于批量合成。

Synthesis of novel anticancer drug cabazitaxel

Cabazitaxel, a new treatment option for patients with hormone-refractory metastatic prostate cancer who had been previously treated with a regimen containing the taxane docetaxel, was approved by FDA in 2010. Here,a new route for the synthesis of cabazitaxel（Javanta） starting with 10-deacetylbaccatin Ⅲ （ 10- DAB Ⅲ） was developed. The target compound was prepared from 10-DABⅢ via three steps including meth- ylation,esterification and deprotection. The overall yield was 41.7% and the structures of all the products were characterized by 1H-NMR and MS respectively. The process is suitable for large scale preparation for its advantages of simple operation and relatively low cost.