Page 146 - 精细化工2019年第9期

第 36 卷第 9 期 精 细 化 工 Vol.36, No.9
201 9 年 9 月 FINE CHEMICALS Sept. 2019

医药与日化原料
一种合成 α-鼠胆酸的新方法

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李 阳 ，梁雨烟 ，黄 欢 ，杜荣凯 ，张 雷 1,2*
（1. 华南理工大学 生物科学与工程学院，广东 广州 510006；2. 广东省生物制药工程技术研究中心，
广东 广州 510006）
摘要：以猪去氧胆酸为原料，经酯化、C-6 位选择性氧化、C-7 位羟基化、C-6 位羰基还原和水解等步骤合成 α-
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鼠胆酸，其结构经 HNMR、 CNMR、HRMS 确认，反应总收率达到 28.9%±0.3%。考察了催化剂对中间体Ⅱ
收率的影响和工艺的稳定性；探索了不同氧化剂对中间体Ⅱ中 C-3 和 C-6 位羟基氧化的选择性及收率的影响，
筛选到可高效选择性氧化 C-6 位羟基的氧化剂 2-碘酰基苯甲酸（IBX），同时考察了 IBX 与中间体Ⅱ的物料比对
中间体Ⅲ收率的影响及工艺的稳定性。结果表明：浓盐酸作为催化剂，中间体Ⅱ的收率约 99%；IBX 可以选择
性氧化中间体Ⅱ中 C-6 位羟基，且当 n（中间体Ⅱ）∶n（IBX）=1∶1.20 时，中间体Ⅲ的收率达到 82.3%；获
得了中间体Ⅲ的 X 射线单晶结构，确定了其绝对构型。
关键词：猪去氧胆酸；α-鼠胆酸；选择性氧化；羟基化；水解；医药原料
中图分类号：TQ460.1 文献标识码：A 文章编号：1003-5214 (2019) 09-1874-07

A New Method for the Synthesis of α-Muricholic Acid

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LI Yang , LIANG Yu-yan , HUANG Huan , DU Rong-kai , ZHANG Lei 1,2*
（1. School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006,
Guangdong, China; 2. Guangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals,
Guangzhou 510006, Guangdong, China）
Abstract: α-Muricholic acid was synthesized from hyodeoxycholic acid via esterification, selective C-6
oxidation, C-7 hydroxylation, C-6 carbonyl reduction and hydrolysis reactions. The resulting product was
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confirmed by HNMR, CNMR and HRMS. The overall yield of product from hyodeoxycholic acid was
28.9%±0.3%. The effect of different catalysts on the yield of intermediateⅡ was investigated as well as the
process stability of esterification was tested. Different oxidants for the selective oxidation of C-3 or C-6
hydroxyl group in intermediate Ⅱ were screened. 2-Iodoxybenzoic acid (IBX) was approved to be good
candidate in selective oxidation of the C-6 hydroxyl group. The effect of molar ratio of Ⅱ to IBX on the
yield of intermediate Ⅲ was studied and the process stability of the reaction was explored. The results
showed that the yield of intermediate Ⅱ was 99% when concentrated HCl was used as catalyst. The yield
of intermediate Ⅲ was up to 82.3% when the molar ratio of Ⅱ to IBX was 1: 1.20. The absolute
configuration of intermediate Ⅲ was determined by single-crystal X-ray diffraction and it was as expected.
Key words: hyodeoxycholic acid; α-muricholic acid; selective oxidation; hydroxylation; hydrolysis; drug
materials

鼠胆酸（Muricholic acid，MCA）是重要的 括 α-鼠胆酸（α-MCA）、β-鼠胆酸（β-MCA）和 ω-
胆汁酸之一，其与猪胆酸(Hyocholic acid，HCA) 鼠胆酸（ω-MCA）这 3 种手性异构体，结构如下
的主要区别在于 6-OH 及 7-OH 的构型不同，且包 所示。

收稿日期：2019-05-16; 定用日期：2019-07-03; DOI: 10.13550/j.jxhg.20190443
基金项目：广东省科技厅科技计划项目资金资助（2016A010121004）
作者简介： 李 阳（1991—），男，硕士生，E-mail：liyanggood@126.com。联系人：张 雷（1971—），男，教授，E-mail：lzhangce@scut.edu.cn。