Preparation and physicochemical properties of natural (23R)-3α,7α,23- and (23R)-3α,12α,23-trihydroxylated bile acids and their (23S)-epimers

Abstract

By submitting the ketene silyl acetyl (5a) generated from 3α,7α-dihydroxy-5β-cholan-24-oic acid [chenodeoxycholic acid (1a)], to a variety of oxidants, a new efficient route to (23R)-3α,7α,23-trihydroxy-5β-cholan-24-oic acid [phocaecholic acid, (3a)] and its (23S)-epimer (4a) has been developed. By this route, the first synthesis of 3α,12α,23-trihydroxy-5β-cholan-24-oic acid (bitocholic acid) has been achieved and the stereochemistry at C-23 conclusively assigned as R. Aqueous physical chemical properties of (3a) have been studied and compared with those of (1a) and 3α,7α,12α-trihydroxy-5β-cholan-24-oic acid [cholic acid, (1b)], in order to gain insight into the influence of the hydroxy group at C-23 on the physical properties of bile acids.