Bile acids with a cyclopropyl-containing side chain. 1. Preparation and properties of 3 alpha, 7 beta-dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid.
3 alpha, 7 beta-Dihydroxy-22, 23-methylene-5 beta-cholan-24-oic acid (5), a side-chain cyclopropyl analogue of ursodeoxycholic acid (1b), has been prepared by the cyclopropanation of 3 alpha, 7 beta-diacetoxy-24-nor-5 beta-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 pKa with respect to compound 1b. Cyclopropyl acid 5 is taken up efficiently by rat liver and promptly secreted into bile. It is partially (70%) 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.
D000818:Animals; D001646:Bile / Q000378:metabolism; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008823:Micelles; D010477:Perfusion; D051381:Rats; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014867:Water
D008823:Micelles; D003840:Deoxycholic Acid; D014867:Water; D014580:Ursodeoxycholic Acid; C041489:3,7-dihydroxy-22,23-methylenecholan-24-oic acid