Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review
Ursodeoxycholic acid (UDCA) is a pharmaceutical ingredient widely used in clinics. As bile acid it solubilizes cholesterol gallstones and improves the liver function in case of cholestatic diseases. UDCA can be obtained from cholic acid (CA), which is the most abundant and least expensive bile acid...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Beilstein-Institut
2018-02-01
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| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.14.33 |
| _version_ | 1818431779172777984 |
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| author | Fabio Tonin Isabel W. C. E. Arends |
| author_facet | Fabio Tonin Isabel W. C. E. Arends |
| author_sort | Fabio Tonin |
| collection | DOAJ |
| description | Ursodeoxycholic acid (UDCA) is a pharmaceutical ingredient widely used in clinics. As bile acid it solubilizes cholesterol gallstones and improves the liver function in case of cholestatic diseases. UDCA can be obtained from cholic acid (CA), which is the most abundant and least expensive bile acid available. The now available chemical routes for the obtainment of UDCA yield about 30% of final product. For these syntheses several protection and deprotection steps requiring toxic and dangerous reagents have to be performed, leading to the production of a series of waste products. In many cases the cholic acid itself first needs to be prepared from its taurinated and glycilated derivatives in the bile, thus adding to the complexity and multitude of steps involved of the synthetic process. For these reasons, several studies have been performed towards the development of microbial transformations or chemoenzymatic procedures for the synthesis of UDCA starting from CA or chenodeoxycholic acid (CDCA). This promising approach led several research groups to focus their attention on the development of biotransformations with non-pathogenic, easy-to-manage microorganisms, and their enzymes. In particular, the enzymatic reactions involved are selective hydrolysis, epimerization of the hydroxy functions (by oxidation and subsequent reduction) and the specific hydroxylation and dehydroxylation of suitable positions in the steroid rings. In this minireview, we critically analyze the state of the art of the production of UDCA by several chemical, chemoenzymatic and enzymatic routes reported, highlighting the bottlenecks of each production step. Particular attention is placed on the precursors availability as well as the substrate loading in the process. Potential new routes and recent developments are discussed, in particular on the employment of flow-reactors. The latter technology allows to develop processes with shorter reaction times and lower costs for the chemical and enzymatic reactions involved. |
| first_indexed | 2024-12-14T15:54:43Z |
| format | Article |
| id | doaj.art-b9cdeead6a124bf0b1048764d5af16a6 |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-14T15:54:43Z |
| publishDate | 2018-02-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-b9cdeead6a124bf0b1048764d5af16a62022-12-21T22:55:18ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972018-02-0114147048310.3762/bjoc.14.331860-5397-14-33Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical reviewFabio Tonin0Isabel W. C. E. Arends1Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The NetherlandsDepartment of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The NetherlandsUrsodeoxycholic acid (UDCA) is a pharmaceutical ingredient widely used in clinics. As bile acid it solubilizes cholesterol gallstones and improves the liver function in case of cholestatic diseases. UDCA can be obtained from cholic acid (CA), which is the most abundant and least expensive bile acid available. The now available chemical routes for the obtainment of UDCA yield about 30% of final product. For these syntheses several protection and deprotection steps requiring toxic and dangerous reagents have to be performed, leading to the production of a series of waste products. In many cases the cholic acid itself first needs to be prepared from its taurinated and glycilated derivatives in the bile, thus adding to the complexity and multitude of steps involved of the synthetic process. For these reasons, several studies have been performed towards the development of microbial transformations or chemoenzymatic procedures for the synthesis of UDCA starting from CA or chenodeoxycholic acid (CDCA). This promising approach led several research groups to focus their attention on the development of biotransformations with non-pathogenic, easy-to-manage microorganisms, and their enzymes. In particular, the enzymatic reactions involved are selective hydrolysis, epimerization of the hydroxy functions (by oxidation and subsequent reduction) and the specific hydroxylation and dehydroxylation of suitable positions in the steroid rings. In this minireview, we critically analyze the state of the art of the production of UDCA by several chemical, chemoenzymatic and enzymatic routes reported, highlighting the bottlenecks of each production step. Particular attention is placed on the precursors availability as well as the substrate loading in the process. Potential new routes and recent developments are discussed, in particular on the employment of flow-reactors. The latter technology allows to develop processes with shorter reaction times and lower costs for the chemical and enzymatic reactions involved.https://doi.org/10.3762/bjoc.14.33bile acidsbiotransformationhydroxysteroid dehydrogenasesproduction processUDCA |
| spellingShingle | Fabio Tonin Isabel W. C. E. Arends Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review Beilstein Journal of Organic Chemistry bile acids biotransformation hydroxysteroid dehydrogenases production process UDCA |
| title | Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review |
| title_full | Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review |
| title_fullStr | Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review |
| title_full_unstemmed | Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review |
| title_short | Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review |
| title_sort | latest development in the synthesis of ursodeoxycholic acid udca a critical review |
| topic | bile acids biotransformation hydroxysteroid dehydrogenases production process UDCA |
| url | https://doi.org/10.3762/bjoc.14.33 |
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