Abstract: Aiming at process optimization of synthesizes of 7′-Br-anhydrovinblastine from anhydrovinblastine; experiment factors and levels were firstly selected by single factor tests. According to the Box-Benhnken design principle，the method of response surface method with 3 factors and 3 levels was used. The factors influencing the technological parameters were determined by means of regression analysis. Response surfaces were finally graphed with the yield as the response value. The synthesis conditions were optimized as follows：reaction reagent was NBS，stoichiometric proportion between NBS and anhydrovinblastine was 1.07; the dosage of TFA was 22 mL/L; reaction temperature was －68 ℃ and duration was 90 min. The total yield of anhydrovinblastine to vinorelbine reached 70.56%.

摘要： 采用响应面分析方法，对以脱水长春碱为原料合成7′-Br-脱水长春碱过程进行最佳工艺条件的探索。在单因素实验基础上，根据Box-Benhnken实验设计原理，采用三因素三水平的响应面分析法，研究了各个因素及其交互作用后，得到了合成7′-Br-脱水长春碱的最佳工艺条件：以二氯甲烷为溶剂，采用NBS为溴代剂，其用量与底物的物质的量比为1.07∶1，TFA的加入量22 mL/L，在－68 ℃下反应90 min，终止反应后，得到卤代产物。产物经过缩环反应得到长春瑞滨，总收率达到70.56%，高于文献报道最大值。