The enzymic and chemical synthesis of ursodeoxycholic and chenodeoxycholic acid from cholic acid.
Three approaches to the synthesis of ursodeoxycholic acid (UDC) from cholic acid have been investigated: (i) oxidation of cholic acid to 3 alpha, 7 alpha-dihydroxy-12 keto-5 beta-cholanoic acid (12K-CDC) with Clostridium group P 12 alpha-hydroxysteroid dehydrogenase (HSDH), isomerization of 12K-CDC to 3 alpha, 7 beta-dihydroxy-12 keto-5 beta-cholanoic acid (12K-UDC) with Clostridium absonum 7 alpha- and 7 beta-HSDH and reduction of 12K-UDC by Wolff-Kishner to UDC; (ii) isomerization of cholic acid to ursocholic acid (UC) by C. absonum 7 alpha- and 7 beta-HSDH, oxidation of UC to 12K-UDC with Clostridium group P 12 alpha-HSDH and Wolff-Kishner reduction of 12K-UDC to UDC; (iii) oxidation of cholic acid to 12K-CDC by Clostridium group P 12 alpha-HSDH, Wolff-Kishner reduction of 12K-CDC to chenodeoxycholic acid (CDC) and isomerization of CDC to UDC using whole cell cultures of C. absonum. In the first two approaches (using cell free systems) the yields of desired product were relatively low primarily due to the formation of various side products. The third method proved the most successful giving an overall yield of 37% (UDC) whose structure was verified by mass spectroscopy of the methyl ester.
D002478:Cells, Cultured; D002635:Chenodeoxycholic Acid / Q000378:metabolism*; D002793:Cholic Acids / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D003013:Clostridium / Q000201:enzymology; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D066298:In Vitro Techniques; D007536:Isomerism; D010084:Oxidation-Reduction; D014580:Ursodeoxycholic Acid / Q000378:metabolism*
D002793:Cholic Acids; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D006913:Hydroxysteroid Dehydrogenases