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目的制备甘草次酸30位酰胺类衍生物N-β-羟乙基-18β-甘草次酸-30-酰胺(Ⅲ)和N-β-羟乙基-18α-甘草次酸-30-酰胺(IV),并优化其制备工艺。方法 18β-甘草次酸(18β-GA,Ⅰ)经高温碱催化进行构型转化反应得到18α-甘草次酸(18α-GA,Ⅱ);化合物Ⅰ、Ⅱ分别与2-氨基乙醇缩合制得目标化合物Ⅲ、Ⅳ;用常规光谱方法鉴定结构;同时考察不同种类缩合剂、溶剂量、物料比、处理方法对目标化合物产率的影响,筛选最佳制备工艺。结果目标化合物Ⅲ、Ⅳ的产率分别为63%、48%。结论确定以EDCI、HOBt、DMAP为催化系统,配料比分别为18β-GA-EDCI-HOBt-DMAP(1∶1.5∶1∶0.5)及18α-GA-EDCI-HOBt-DMAP(1∶2∶1∶0.5),二氯甲烷为溶剂,化合物Ⅲ、Ⅳ的反应时间分别为18、28h,所用工艺是制备甘草次酸30位酰胺类衍生物的较好工艺。
OBJECTIVE To prepare glycyrrhetinic acid 30-amide derivatives N-β-hydroxyethyl-18β-glycyrrhetinic acid-30-amide (Ⅲ) and N-β-hydroxyethyl-18α-glycyrrhetinic acid-30- IV), and optimize its preparation process. Methods The 18α-glycyrrhetinic acid (18α-GA, Ⅱ) was synthesized by 18β-glycyrrhetinic acid (18β-GA, Ⅰ) by high temperature base catalysis. The compounds Ⅰ and Ⅱ were condensed with 2-aminoethanol respectively Compounds Ⅲ and Ⅳ were identified by conventional spectroscopic methods. Meanwhile, the effects of different kinds of condensing agents, solvent amount, material ratio and treatment methods on the yield of target compounds were investigated, and the optimum preparation process was screened. Results The yields of target compounds III and IV were 63% and 48%, respectively. Conclusion The results showed that the optimal conditions were 18:1-GA-EDCI-HOBt-DMAP (1:1.5:1:0.5) and 18α-GA-EDCI-HOBt-DMAP : 0.5) and dichloromethane as solvent. The reaction time of compound Ⅲ and Ⅳ were 18 and 28 h, respectively. The process used was a better process for preparing amides derivatives of glycyrrhetinic acid at position 30.