Dai Mohan, Xu Binpeng, Guo Qing, Wan Junfen, Cao Xuejun
State Key Laboratory of Bioreactor Engineering, Department of Bioengineering, East China University of Science and Technology, Shanghai, 200237, China.
Bioresour Bioprocess. 2023 Aug 7;10(1):48. doi: 10.1186/s40643-023-00668-x.
Ursodeoxycholic acid (UDCA) is not only safer than chenodeoxycholic acid in the treatment of hepatobiliary diseases, but also has a wide range of applications in Acute Kidney Injury and Parkinson's Disease. The purpose of this experiment is to improve the conversion rate of 7-ketocholic acid (7K-LCA) and the yield of ursodeoxycholic acid in aprotic solvents during electrochemical reduction process. Three aprotic solvents were investigated as electrolytes. 1,3-Dimethyl-2-imidazolidinone (DMI) has a stable five-membered ring structure, and 7K-LCA has undergone two nucleophilic reactions and "Walden" inversion, the 7K-LCK was stereoselectively reduced to UDCA. Hexamethylphosphoramide (HMPA) and 1,3-methyl-3,4,5,6-Tetrahydro-2(1H)-pyrimidinone (DMPU) can be attacked by chloride ions to produce by-products. Molecular orbital theory-based simulations were conducted to study the reducibility of three aprotic solvents [hexamethylphosphoramide (HMPA), 1,3-methyl-3,4,5,6-Tetrahydro-2(1H)-pyrimidinone (DMPU), and 1,3-Dimethyl-2-imidazolidinone (DMI)] in combination with experiments. Choose the best solvent based on the simulation results, the electrolysis reaction can be carried out by applying current and voltage when lithium chloride is used as electrolytes. Calculations using Materials Studio showed that Cu, Pb, Hg-Cu, and Ni exhibited the highest binding energies to the substrate in this system. Using Cu as the electrode when the solvent is a 1:1 mix of DMI and HMPA, the conversion rate of 7-ketocholic acid (could reach 98%, the yield of ursodeoxycholic acid was up to 80%. Under the same conditions, linear voltammetry was performed on the electrochemical workstation to study the electrolysis behavior, and the obtained results were consistent with the experiment.
熊去氧胆酸（UDCA）在肝胆疾病治疗中不仅比鹅去氧胆酸更安全，而且在急性肾损伤和帕金森病中也有广泛应用。本实验的目的是提高非质子溶剂中7-酮胆酸（7K-LCA）在电化学还原过程中的转化率以及熊去氧胆酸的产率。研究了三种非质子溶剂作为电解质。1,3-二甲基-2-咪唑啉酮（DMI）具有稳定的五元环结构，7K-LCA发生了两次亲核反应和“瓦尔登”反转，7K-LCK被立体选择性还原为UDCA。六甲基磷酰胺（HMPA）和1,3-甲基-3,4,5,6-四氢-2(1H)-嘧啶酮（DMPU）会受到氯离子攻击产生副产物。结合实验，基于分子轨道理论进行模拟以研究三种非质子溶剂[六甲基磷酰胺（HMPA）、1,3-甲基-3,4,5,6-四氢-2(1H)-嘧啶酮（DMPU）和1,3-二甲基-2-咪唑啉酮（DMI）]的还原性。根据模拟结果选择最佳溶剂，当使用氯化锂作为电解质时，通过施加电流和电压进行电解反应。使用Materials Studio进行的计算表明，在该体系中Cu、Pb、Hg-Cu和Ni与底物的结合能最高。当溶剂为DMI和HMPA的1:1混合物时，使用Cu作为电极，7-酮胆酸的转化率可达98%，熊去氧胆酸的产率高达80%。在相同条件下，在电化学工作站上进行线性伏安法研究电解行为，所得结果与实验一致。
