Synthesis of ursodeoxycholic acid by electrochemical stereoselective reduction of 7-ketolithocholic acid in aprotic solvents

Abstract A novel method of producing ursodeoxycholic acid was developed through electrochemical stereoselective reduction of 7-ketolithocholic acid (7K-LCA) in a undivided electrolytic cell and aprotic solvents as electrolyte. Five aprotic solvents were investigated as electrolytes, the simple struc...

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Autores principales:	Jinxue Shen, Dongdong Dong, Zefa Wang, Junfen Wan, Xuejun Cao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b18e980beae43e0b67f86527b7408c4
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spelling	oai:doaj.org-article:3b18e980beae43e0b67f86527b7408c42021-12-02T16:28:06ZSynthesis of ursodeoxycholic acid by electrochemical stereoselective reduction of 7-ketolithocholic acid in aprotic solvents10.1038/s41598-021-95577-42045-2322https://doaj.org/article/3b18e980beae43e0b67f86527b7408c42021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95577-4https://doaj.org/toc/2045-2322Abstract A novel method of producing ursodeoxycholic acid was developed through electrochemical stereoselective reduction of 7-ketolithocholic acid (7K-LCA) in a undivided electrolytic cell and aprotic solvents as electrolyte. Five aprotic solvents were investigated as electrolytes, the simple structure of dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF) were easily attacked by chloride ions and undergo nucleophilic reactions, resulting in no target reactions. The structure of hexamethylphosphoric triamide (HMPA) and 1,3-methyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinone (DMPU) is relatively complex, but chloride ions can still attack them, and it was easier for 7K-LCA to directly undergo a reduction reaction under the action of electric current, because of the small steric hindrance of chenodeoxycholic acid (CDCA), 7K-LCA was stereoselectively reduced to CDCA. Due to the stable structure of the five-membered imidazole ring of 1,3-dimethyl-2-imidazolidinone (DMI), 7K-LCA undergoes two nucleophilic and a "Walden inversion", thereby stereoselective reduction of 7K-LCA to UDCA. In DMI, the highest conversion rate of 7K-LCA was 58.3%, the yield of UDCA was 34.9%, ee value was 100%. Linear sweep voltammetry was used to explore the electrochemical behavior of the reaction, and the electrolysis results were consistent with the linear sweep voltammetry. The product was characterized by using IR, 1H NMR and 13C NMR, it confirm the product was UDCA. The method developed in this paper provides a relatively environmentally friendly and low-consumption method for large-scale production of ursodeoxycholic acid, and provides a valuable reference for the asymmetric electrochemical reduction of ketone groups.Jinxue ShenDongdong DongZefa WangJunfen WanXuejun CaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jinxue Shen Dongdong Dong Zefa Wang Junfen Wan Xuejun Cao Synthesis of ursodeoxycholic acid by electrochemical stereoselective reduction of 7-ketolithocholic acid in aprotic solvents
description	Abstract A novel method of producing ursodeoxycholic acid was developed through electrochemical stereoselective reduction of 7-ketolithocholic acid (7K-LCA) in a undivided electrolytic cell and aprotic solvents as electrolyte. Five aprotic solvents were investigated as electrolytes, the simple structure of dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF) were easily attacked by chloride ions and undergo nucleophilic reactions, resulting in no target reactions. The structure of hexamethylphosphoric triamide (HMPA) and 1,3-methyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinone (DMPU) is relatively complex, but chloride ions can still attack them, and it was easier for 7K-LCA to directly undergo a reduction reaction under the action of electric current, because of the small steric hindrance of chenodeoxycholic acid (CDCA), 7K-LCA was stereoselectively reduced to CDCA. Due to the stable structure of the five-membered imidazole ring of 1,3-dimethyl-2-imidazolidinone (DMI), 7K-LCA undergoes two nucleophilic and a "Walden inversion", thereby stereoselective reduction of 7K-LCA to UDCA. In DMI, the highest conversion rate of 7K-LCA was 58.3%, the yield of UDCA was 34.9%, ee value was 100%. Linear sweep voltammetry was used to explore the electrochemical behavior of the reaction, and the electrolysis results were consistent with the linear sweep voltammetry. The product was characterized by using IR, 1H NMR and 13C NMR, it confirm the product was UDCA. The method developed in this paper provides a relatively environmentally friendly and low-consumption method for large-scale production of ursodeoxycholic acid, and provides a valuable reference for the asymmetric electrochemical reduction of ketone groups.
format	article
author	Jinxue Shen Dongdong Dong Zefa Wang Junfen Wan Xuejun Cao
author_facet	Jinxue Shen Dongdong Dong Zefa Wang Junfen Wan Xuejun Cao
author_sort	Jinxue Shen
title	Synthesis of ursodeoxycholic acid by electrochemical stereoselective reduction of 7-ketolithocholic acid in aprotic solvents
title_short	Synthesis of ursodeoxycholic acid by electrochemical stereoselective reduction of 7-ketolithocholic acid in aprotic solvents
title_full	Synthesis of ursodeoxycholic acid by electrochemical stereoselective reduction of 7-ketolithocholic acid in aprotic solvents
title_fullStr	Synthesis of ursodeoxycholic acid by electrochemical stereoselective reduction of 7-ketolithocholic acid in aprotic solvents
title_full_unstemmed	Synthesis of ursodeoxycholic acid by electrochemical stereoselective reduction of 7-ketolithocholic acid in aprotic solvents
title_sort	synthesis of ursodeoxycholic acid by electrochemical stereoselective reduction of 7-ketolithocholic acid in aprotic solvents
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3b18e980beae43e0b67f86527b7408c4
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Synthesis of ursodeoxycholic acid by electrochemical stereoselective reduction of 7-ketolithocholic acid in aprotic solvents

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