Abstract
AbstractUrsodeoxycholic 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.
Graphical Abstract
Publisher
Springer Science and Business Media LLC
Subject
Renewable Energy, Sustainability and the Environment,Biomedical Engineering,Food Science,Biotechnology
Reference23 articles.
1. Chen W, Hu D, Liu G (2021) Synthesis of ursodeoxycholic acid from dehydroiso-androsterone 3-acetate. Chem J Chin Univ Chin 42:2782–2788. https://doi.org/10.7503/cjcu20210277
2. Cole EB, Bocarsly A, Bocarsly AB, Cole E (xxxx) Heterocycle catalyzed electrochemical reduction of a carbonyl compound, comprises introducing carbonyl compound into solution of e.g. electrolyte in divided electrochemical cell, varying and separating obtained aldehyde compounds. Liquid Light Inc; Univ Princeton
3. Hashiba H, Yotsuhashi S, Deguchi M, Yamada Y (2016) Systematic analysis of electrochemical CO2 reduction with various reaction parameters using combinatorial reactors. ACS Comb Sci 18:203–208. https://doi.org/10.1021/acscombsci.6b00021
4. Hattori M, Mikami K, Sekine T (xxxx) Selective redn. of bile acid having keto gp. at 7-position by reacting bile acid in presence of base using nickel catalyst in normal lower alcohol. Tanabe Co., Tokyo
5. Huang X, Cao X (2015a) Preparation of ursodeoxycholic acid from 7-ketone lithocholic acid by stereoselective electroreduction. Bioresour Bioprocess 2:1–9. https://doi.org/10.1186/s40643-015-0058-4