响应面法优化布比卡因消旋体超声辅助手性拆分

Optimization of ultrasonic-assisted chiral resolution of bupivacaine with response surface method

为了研究超声辅助拆分布比卡因消旋体的最佳工艺条件,以左旋布比卡因的纯度和收率为指标,根据Box-Benhnken中心组合实验设计原理,采用响应面分析法,对影响布比卡因拆分效果的主要因素(超声波功率、溶剂异丙醇用量及反应温度)进行优化,得到布比卡因消旋体超声辅助拆分的最优工艺条件为:超声功率300 W,异丙醇用量4.8 mL/g布比卡因消旋体,反应温度60℃。在此条件下拆分,左旋布比卡因的收率预测值为90.4%,纯度预测值为96.4%,验证实验值分别为收率89.5%,纯度96.2%,因此,响应面法用于布比卡因拆分条件的优化是可行的。与文献报道结果比较,超声波对布比卡因消旋体非对映体结晶拆分具有明显的强化作用。

To study the optimum ultrasonic-assisted chiral resolution condition of bupivacaine race- mate, response surface methodology （RSM） based on Box-Benhnken experimental design model was applied to optimize the conditions of chiral resolution. The effects of independent variables, inclu- ding ultrasound power, solvent amount and resolution temperature were investigated, and the resolu- tion effect was evaluated by purity and yield of levobupivacaine. The optimal resolution condition for levobupivacaine within the experimental range of the variables researched was as follows： ultrasound power of 300 W, solvent amount of 4. 8 mL/g racemate and resolution temperature of 60 ~C. Under this condition, the yield and purity of levobupivacaine were predicted to be 90. 4% and 96. 4% respectively, and corresponding experiment results were 89.5% and 96. 2% , which demonstrated that it was fea- sible to optimize the resolution of bupivacaine by using RSM. Compared with the reported results, ultrasonic-assisted has obvious strengthening effects on chiral resolution of bupivacaine racemate.