Preparation and characterization of 3-monohydroxylated bile acids of different side chain length and configuration at C-3. Novel approach to the synthesis of 24-norlithocholic acid.

Abstract

A series of 3-monohydroxylated bile acids, in unlabeled and radioactive form, of varying side chain length and configuration at C-3 has been synthesized and rigorously characterized. They include: 3 alpha- and 3 beta-hydroxy-5 beta-androstane-17 beta-carboxylic acids (C20); 3 alpha- and 3 beta-hydroxy-5 beta-pregnan-21-oic acids (C21); 3 alpha- and 3 beta-hydroxy-23,24-bisnor-5 beta-cholan-22-oic acids (C22); 3 alpha- and 3 beta-hydroxy-24-nor-5 beta-cholan-23-oic acids (C23, norlithocholic and isonorlithocholic acids); and 3 beta-hydroxy-5 beta-cholan-24-oic acid (C24, isolithocholic acid). A novel approach to the degradation of lithocholic acid acetate to 24-norlithocholic acid is described. This degradation involves the photochemical modification of a Hunsdiecker reaction and Kornblum oxidation of the intermediate 23-bromide. The availability of these compounds makes it possible to study the metabolism and biological effects of short chain bile acids.