Vonafexor(EYP001)的合成  

Synthesis of Vonafexor(EYP001)

作　　者：姜珊 刘洪涛[2] 田文华 李文燕[1] JIANG Shan;LIU Hongtao;TIAN Wenhua;LI Wenyan(College of Chemistry and Materials Science,Hebei Normal University,Hebei Key Laboratory of Organic Functional Molecules,Hebei Shiiazhuang 050024,China;Department of Pharmacy,Hebei General Hospital,Hebei Shijiazhuang 050051,China)

机构地区：[1]河北师范大学化学与材料科学学院,河北省有机功能分子重点实验室,河北石家庄050024 [2]河北省人民医院药学部,河北石家庄050051

出　　处：《河北师范大学学报（自然科学版）》2022年第4期386-390,共5页Journal of Hebei Normal University：Natural Science

基　　金：河北省自然科学基金京津冀基础研究合作专项(H2019205318,19JCZDC63900);河北师范大学研究生创新资助基金(CXZZSS2021057)。

摘　　要：以5-溴水杨醛为起始原料,与溴乙酸乙酯通过2步反应环合生成5-溴苯并呋喃-2-甲酸乙酯,再与1-Boc哌嗪反应生成5-(4-叔丁氧羰基哌嗪)苯并呋喃-2-甲酸乙酯;接着经N-氯代丁二酰亚胺(NCS)氯代得到4-氯-5-(4-叔丁氧羰基哌嗪)苯并呋喃-2-甲酸乙酯;最后脱去Boc保护基,与2,6-二氯苯磺酰氯反应得到4-氯-5-[4-(2,6-二氯苯磺酰基)-1-哌嗪基]苯并呋喃-2-甲酸乙酯,水解后得到目标化合物EYP001,总收率为58.3%.In this paper,5-bromosalicylic aldehyde was used as the starting material and cyclized with ethyl bromoacetate through a two-step reaction.The ethyl 5-bromobenzofuran-2-carboxylate was achieved,which was then reacted with 1-Boc piperazine to yield tert-butyl 4-(2-(ethoxycarbonyl)benzofuran-5-yl)piperazine-1-carboxylate.A chlorination reaction with N-chlorosuccinimide(NCS)was followed to give tertbutyl 4-(4-chloro-2-(ethoxycarbonyl)benzofuran-5-yl)piperazine-1-carboxylate whose Boc protecting group was removed afterwards.Finally EYP001 was obtained by a sulfonation reaction with 2,6-dichlorobenzenesulfonyl chloride and then hydrolyzed with a total yield of 58.3%.

关 键 词：Vonafexor EYP001 法尼醇X受体激动剂 合成 

分 类 号：R914.5[医药卫生—药物化学]