Print Email Facebook Twitter Latest development in the synthesis of ursodeoxycholic acid (UDCA) Title Latest development in the synthesis of ursodeoxycholic acid (UDCA): A critical review Author Tonin, F. (TU Delft BT/Biocatalysis) Arends, I.W.C.E. (TU Delft BT/Biotechnologie) Department BT/Biotechnologie Date 2018-02-20 Abstract 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. Subject Bile acidsBiotransformationHydroxysteroid dehydrogenasesProduction processUDCA To reference this document use: http://resolver.tudelft.nl/uuid:b8240342-c6f0-49b4-90b4-2de4b35fd808 DOI https://doi.org/10.3762/bjoc.14.33 ISSN 1860-5397 Source Beilstein Journal of Organic Chemistry, 14, 470-483 Part of collection Institutional Repository Document type review Rights © 2018 F. Tonin, I.W.C.E. Arends Files PDF 1860_5397_14_33.pdf 1.9 MB Close viewer /islandora/object/uuid:b8240342-c6f0-49b4-90b4-2de4b35fd808/datastream/OBJ/view