The Method Of Prepareing Ursodeoxycholic Acid From Chenodeoxycholic Acid

Ursodeoxycholic acid was prepared from chenodeoxycholic acid though two-step reaction, that is the first oxidation of chenodeoxycholic acid obtained an intermediate named 7-ketolithocholic acid, then asymmetric reduction of 7-ketolithocholic acid to ursodeoxycholic acid.The first step is the electrochemical generated Br2 from Br- oxidate 7-hydroxy of chenodeoxycholic acid and the product is 7-ketolithocholic acid, Br2 is reduced to Br- which is reoxidation on the electrode, that means, Br2 is recycling. Three electrodes, Ru/Ti, Graphite, and PbO2/Ti are tested in the electrolysis system by cyclic voltammetry study, cyclic voltammetry graphs confirmed indirect electrooxidation reaction route of chenodeoxycholic acid. Another work is the pilot of the reaction by adding a certain amount of material, the stability conditions for the batch electrolysis is, total electrolysis time of 8h, current 10A. As a result, chenodeoxycholic acid is completely converted, the conversion ratio of 7-ketolithocholic acid is higher than 95%, byproduct is 3,7-dionelithocholic acidThe second step is the reduction reaction of 7-ketolithocholic acid, electrochemical and catalytic transfer hydrogenation (CTH) are selected. Cyclic voltammetry study of lead and nickel in the H-divided cell electrolysis system provides a guidance of further optimization of conditions. Also Ni-Al alloy, Pd/C, Ru/C and Raney Ni are used as catalyst respectively for catalytic transfer hydrogenation of 7-ketolithocholic acid. The results show Raney nickel is better, the yield of ursodeoxycholic acid can be up to 90% or more. Optimum conditions for Raney Ni reaction are temperature 40℃, time 16h, m(Raney Ni)/m(7-ketolithocholic acid) =4 (Raney Ni referred to wet weight). Under such conditions, ursodeoxycholic acid yield is 92% which means a better stereoselective reduction.After recrystallization, IR,1H NMR and 13C NMR are introduced, the graphs demonstrate the product is ursodeoxycholic acid.