New bile acid analogs: 3 alpha, 7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acid, 3 alpha, 7 beta-dihydroxy-7 alpha-methyl-5 beta-cholanoic acid, and 3 alpha-hydroxy-7 xi-methyl-5 beta-cholanoic acid

Abstract

Methods are described for the chemical synthesis of three new bile acid analogs, namely, 3 alpha, 7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acid, 3 alpha, 7 beta-dihydroxy-7 alpha-methyl-5 beta-cholanoic acid and 3 alpha-hydroxyl-7 xi-methyl-5 beta-cholanoic acid. The starting material, 2-(3 alpha, 7 xi-dihydroxy-7 xi-methyl-24-nor-5 beta- cholanyl )-4, 4-dimethyl-2-oxazoline upon mild hydrolysis in aqueous HCl yields the two epimeric 3 alpha, 7-dihydroxy-7-methyl-5 beta-cholanoic acids which can be separated as the methyl esters by silica gel column chromatography. More rigorous hydrolysis in boiling methanolic HCl yields a mixture of unsaturated compounds which can be separated as their methyl esters into three fractions by silica gel-AgNO3 column chromatography. The fractions containing 3 alpha-hydroxy-7-methyl-5 beta-chol-6-enoic acid and 3 alpha-hydroxy-7-methylene-5 beta-cholanoic acid when subjected to catalytic hydrogenation yield 3 alpha-hydroxy-7 xi-methyl-5 beta-cholanoic acid.