Potential Bile Acid Metabolites. 25. Synthesis and Chemical Properties of Stereoisomeric 3α,7α,16- and 3α,7α,15-Trihydroxy-5β-cholan-24-oic Acids

Abstract

Epimeric 3α,7α,16- and 3α,7α,15-trihydroxy-5β-cholan-24-oic acids and some related compounds were synthesized from chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), respectively. The key reaction involved one-step remote oxyfunctionalization of unactivated methine carbons at C-17 of CDCA and at C-14 of UDCA as their methyl ester-peracetate derivatives with dimethyldioxirane (DMDO). After dehydration of the resulting 17α- and 14α-hydroxy derivatives with POCl₃ or conc. H₂SO₄, the respective Δ¹⁶- and Δ¹⁴-unsaturated products were subjected to hydration via hydroboration followed by oxidation to yield the 3,7,16- and 3,7,15-triketones, respectively. Stereoselective reduction of the respective triketones with tert-butylamine-borane complex afforded the epimeric 3α,7α,16- or 3α,7α,15-trihydroxy derivatives exclusively. A facile formation of the corresponding ε-lactones between the side chain carboxyl group at C-24 and the 16α- (or 16β-) hydroxyl group in bile acids is also clarified.