多西他赛合成工艺  

Study on Synthesis of Docetaxel

作　　者：徐少杰[1] 袁建勇[1] 周辉[1] 甘勇军[1] 李勤耕[1] 

机构地区：[1]重庆医科大学药学院,重庆400016

出　　处：《科技导报》2010年第13期82-86,共5页Science & Technology Review

基　　金：国家自然科学基金项目(20902114)

摘　　要：采用新型合成工艺,以求在高收率的基础上制备高纯度的多西他赛。以10-DABIII为起始原料,经氯甲酸苄酯类化合物酯化反应,制得C-7,C-10-苄氧羰基类保护的10-DABIII,然后与(3R,4S)-1-叔丁氧羰基-4-苯基氮杂环丁烷-2-酮反应,形成2'-(1-乙氧基乙基)-N-脱苯甲酰-N-叔丁氧羰基-C-7,C-10-二-苄氧羰基类-10-去乙酰紫杉醇,又经氢解,得到2'-(1-乙氧基乙基)-N-脱苯甲酰-N-叔丁氧羰基-10-去乙酰紫杉醇,最后经稀酸水解得目标物多西他赛。该工艺探讨了各主要因素对反应过程的影响,确立了各步反应的最佳反应条件。所制备的目标化合物和各中间体经质谱和核磁的确证。实验结果表明该合成工艺具有成本低、易操作、收率高等优点。For the purpose of preparing docetaxel with a high yield, a mild and convenient semi-synthetic process of docetaxel is adopted. The target compound is prepared in four steps. 10-deacetyl baccatin Ⅲ, the starting material, is reacted with benzyl chloroformate to form C-7 and C-10-protected 10-deacetyl baccatin Ⅲ, which is then reacted with （3R,4S）-1-tert-butoxy-carbonyl-3-（1-ethoxy-ethyloxy）-4- phenylaz-etidin-2-one and followed by hydrogenolysis to form a 2′-（1-ethoxy-ethyloxy）-N-off benzoyl-N-tert-butyl carbonyl oxy-gen- 10-deacetyl taxol, and then, the target compound is finally obtained by the acid hydrolysis. The key step is the selective protection of C-7 and C-10 hydroxyl groups of 10-deacetyl baccatin Ⅲ. The effects of main factors on every reaction process are analyzed, to establish the optimized reaction conditions of every step. The target molecules and intermediates are characterized by MS and NMR. The results indicate that the synthetic process is of low cost, easy for handling and with an overall yield of 50% from 10-deacetyl baccatin Ⅲ.

关 键 词：多西他赛 抗癌药 合成 

分 类 号：TQ463.2[化学工程—制药化工]