Different positions of the modified compounds of the pharmaceutical properties are quite different, chenodeoxycholic acid molecules can be modified at the location of C6 hydrogen, C3 hydroxyl, C7 hydroxyl and C24 carboxyl. The acquisition of chenodeoxycholic acid derivatives begins with the modification of these positions.
Cholic acid and chenodeoxycholic acid are natural endogenous ligands of the farnesyl ester derivative X receptor (FXR). 6α-ethyl-chenodeoxycholic acid, also known as obeticholicacid (OCA) is a new derivative of chenodeoxycholic acid, is a highly complex FXR agonist, can promote cholic acid synthesis, treatment of primary biliary cirrhosis and nonalcoholic fatty liver disease, regulation of bile acid and cholesterol within the steady state, so its synthesis method of concern.
Using CDCA as raw material, with sodium hypochlorite solution /sodium bromide solution and tetrabutylammonium bromide oxidation, and then phenyl 24-carboxyl group, to be 7 - keto - lithocholic acid phenyl ester (20), silylene etherification ( 21), followed by an aldol reaction to give (22). The compound (23) was obtained by highly selective reduction of the 7-carbonyl group with NaBH4 / CeCl3 in THF / MeOH at room temperature to give the compound (23), while the hydrogenation ring outside the double bond was simultaneously deprotected to give (19) the yield was 32%.