姚绎炎,杜杨
YAO Yi-yan,DU Yang

• 1:南京理工大学化工学院

摘要(Abstract)：

目的以鹅去氧胆酸为原料合成奥贝胆酸,以期得到更好的奥贝胆酸合成工艺。方法经氧化、酯化、亲电加成、催化加氢和水解还原共5步反应得到奥贝胆酸(6α-乙基鹅去氧胆酸)新的合成工艺,总收率达38%。其结构经1H-NMR、MS分析测试技术确认。结果通过考察各步反应条件,得出最佳工艺条件:氧化反应中,鹅去氧胆酸与N-溴代琥珀酰亚胺物质的量比为1∶1.5;亲电加成中,3α-羟基-7-酮-5β-胆烷酸-24-甲酯与三乙胺与叔丁基二甲基氯硅烷物质的量比为1∶2∶2.2;还原反应中,3α-羟基-6-亚乙基-7-酮-5β-胆烷酸-24-甲酯与硼氢化钠物质的量比为1∶6。
Objective To develop a synthesis technology of obeticholic acid with chenodeoxycholic acid as rawmaterial.To get a better synthesis technology of obeticholic acid.Methods Via the reaction steps of oxidation,esterification,electrophilic addition,catalytic hydrogenation and hydrolysis,obeticholic acid was obtained.The total product yield was 38%.The structure of the target product and intermediates of each reaction step was confirmed by1H-NMR and MS.Conclusions The optimal condition was n(chenodeoxycholic acid) ∶ n(N-bromosuccinimide) = 1 ∶ 1.5 in oxidation reaction; n(3α-hydroxy-7-cheto-5β-cholan-24-oate) ∶ n(triethylamine) ∶ n(tert-butyldimethylsilyl chloride) = 1∶ 2∶ 2.2 in electrophilic addition reaction; n(3α-hydroxy-6-ethylidene-7-cheto-5β-cholan-24-oate) ∶ n(sodium borohydride) = 1∶ 6 in reduction reaction.

关键词(KeyWords)： 鹅去氧胆酸;奥贝胆酸;肝硬化;新型药物
chenodeoxycholic acid;obeticholic acid;biliary cirrhosis;new drug

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 姚绎炎,杜杨
YAO Yi-yan,DU Yang

DOI: 10.14066/j.cnki.cn21-1349/r.2017.01.006

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