选择性肝孤儿受体激动剂5α,6α-环氧胆甾醇前药的合成  

Synthesis of 5α,6α-Epoxycholesterol Prodrugs as Selective Liver Orphan Receptor Agonists

作　　者：徐孝浪 郭晓强 张梦晗[1] 李小红 王虹宇 周闯 何源超 XU Xiaolang;GUO Xiaoqiang;ZHANG Menghan;LI Xiaohong;WANG Hongyu;ZHOU Chuang;HE Yuanchao(College of Pharmacy and Biological Engineering,Chengdu University,Chengdu 610106,Sichuan;Key Laboratory of Medicinal and Edible Plant Resources Development of Sichuan Education Department,Chengdu University,Chengdu 610106,Sichuan;Sichuan Industrial Institute of Antibiotics,Chengdu University,Chengdu 610051,Sichuan)

机构地区：[1]成都大学药学与生物工程学院,四川成都610106 [2]成都大学药食同源植物资源开发四川省高校重点实验室,四川成都610106 [3]成都大学四川抗菌素工业研究所,四川成都610051

出　　处：《四川师范大学学报（自然科学版）》2019年第4期540-544,共5页Journal of Sichuan Normal University（Natural Science）

基　　金：四川省应用基础研究面上项目(2017JY0341);成都市技术创新研发项目(2018-YF05-01510-GX)

摘　　要：以选择性肝孤儿受体(LXR α)激动剂5 α,6 α-环氧胆甾醇( 2a )为先导化合物设计并合成其高生物利用度前药.以胆固醇为起始原料,3-氯过氧苯甲酸( m -CPBA)为氧化剂合成2a ,再对2a 进行酯化、糖苷化反应,分别得到2a 酯化衍生物2a-1、2a-2、2a-3 ,以及糖苷化衍生物2s-1、2s-2、2s-3;对反应条件进行了初步的优化,目标化合物的化学结构经1 HNMR、13C NMR和MS确证.The high bioavailability prodrug was designed and synthesized with the selective hepatic orphan receptor (LXR α) agonist 5 α, 6 α-epoxycholesterol ( 2a ) as the lead compound. With cholesterol as a starting material, 3-chloroperoxybenzoic acid ( m -CPBA) was used as an oxidizing agent to synthesize 2a . Then 2a was esterified and glycosylated to obtain 2a esterification derivatives 2a-1, 2a-2, 2a-3 , and glycosylation derivatives 2s-1, 2s-2 and 2s-3 , respectively. The reaction conditions were initially optimized, and the chemical structure of the target compound was confirmed by 1 H NMR, 13 C NMR and MS.

关 键 词：环氧胆甾醇 肝孤儿受体 前药 环氧化反应 

分 类 号：R914.5[医药卫生—药物化学]