Bile Acids with Cyclopropyl-Containing Side Chain. 1. Preparation and Properties of 3α,7β-Dihydroxy-22,23-methylene-5β-cholan-24-oic Acid

Article abstract of DOI:10.1021/jm00372a007

3α,7β-Dihydroxy-22,23-methylene-5β-cholan-24-oic acid (5), a side-chain cyclopropyl analogue of ursodeoxycholic acid (1b), has been prepared by the cyclopropanation of 3α,7β-diacetoxy-24-nor-5β-chol-22-ene (2) with ethyl diazoacetate, followed by saponification of the resulting cyclopropyl ester (3).The new bile acid presents similar properties to 1b in water.The sodium salt self-aggregates to form micelles at a concentration of 15.5 mM.The cyclopropane ring does not modify the pK_a with respect to compound 1b.Cyclopropyl acid 5 is taken up efficiently by rat liver and promptly secreted into bile.It is partially (70percent) conjugated with taurine.The bile flow and bile acids and phospholipids secretion are stimulated by 5, while the cholesterol secretion is stimulated by 5 to a lesser extent.