Preparation of ursodeoxycholic acid from 7-ketone lithocholic acid by stereoselective electroreduction

Xiaomei Huang,Xuejun Cao

doi:10.1186/s40643-015-0058-4

Abstract

Ursodeoxycholic acid (UDCA) is an important clinical drug in the treatment of liver disease. In previous work, ursodeoxycholic acid was prepared by traditional organic synthesis. The preparation of ursodeoxycholic acid through an electrochemical method with higher stereoselectivity and environmental friendliness is described herein. Dimethyl sulfoxide (DMSO), dimethylformamide (DMF), and N-methyl-2-pyrrolidone (NMP) were used as stereoselectivity additives during electroreduction. With 107.5 mM DMSO in methanol containing potassium bromide and a continuous current of 20 mA, 936 Coulombs was passed into the electrolysis system, achieving 88.5 % conversion of 7-ketone lithocholic acid (7K-LCA), while the yield of UDCA reached 72.8 %. Cyclic voltammetry (CV) was used to explore the electrochemical behavior of the reaction, and the electrolysis results were consistent with the cyclic voltammograms. Ursodeoxycholic acid can be prepared by electroreduction with high stereoselectivity. The method developed here offers a potential application for large-scale production of ursodeoxycholic acid and an interesting reference to asymmetric electrochemical reduction of the keto group.

Highlights

Ursodeoxycholic acid (UDCA) is an important clinical drug in the treatment of liver disease
Ursodeoxycholic acid was synthesized by electroreduction of 7-ketolithocholic acid under certain conditions
The C-7 carbonyl group of 7-ketone lithocholic acid (7K-LCA) is converted to a 7α-hydroxy group, and chenodeoxycholic acid is generated (Fig. 2)

Summary

Introduction

Ursodeoxycholic acid (UDCA) is an important clinical drug in the treatment of liver disease. Ursodeoxycholic acid (3α, 7β-2-hydroxy-5β-bile acid, UDCA) was first found by Shoda [1] in the bile of a black bear. It is used as a clinical drug in the treatment of gallstones, cholecystitis, PBC, and PSC and has broad market prospects and important scientific research value [2,3,4,5,6,7,8,9]. In the previous work [26], our group synthesized 7ketolithocholic acid, which is an important intermediate in ursodeoxycholic acid synthesis, by indirect electrooxidation. UDCA can be obtained stereoselectively in the presence of an aprotic polar solvent (Fig. 1)

Objectives

Methods

Results

Conclusion