Synthesis of 3α,6β,7a,12β- And 3α,6β,7β,12β-tetrahydroxy-5β-cholanoic acids

Article abstract of DOI:10.1016/0039-128X(92)90067-J

Chemical synthesis of 3α,6β,7α,72β- and 3α,6β,7β,12β-tetrahydroxy-5β-cholan-24-oic acids is described. 3α,12β-Dihydroxy-5β-chol-6-en-24-oic acid used as the starting material in the synthesis was prepared via oxidation of 3α,12a-dihydroxy-5β-chol-6-en-24-oic acid 3-hemisuαinate at C-12 followed by reduction with potassium/tertiary amyl alcohol. α-Epoxidation of the ester diacetate of 3a,12βdihydroxy-5β-chol-6-en-24-oic acid with m-chloroperbenzoic acid followed by cleavage of the epoxide with acetic acid and alkaline hydrolysis yielded 3α,6β,7a,12β-tetrahydroxy-5β-cholan-24-oic acid (overall yield 25%). N-Methylmorpholine-N-oxide-catalyzed osmium tetroxide oxidation of the ester diacetate of 3α,12β-dihydroxy-5β-chol-6-en-24-oic acid followed by alkaline hydrolysis yielded 3 α, 6β, 7β, 12β-tetrahydroxy-5β-cholan-24-oic acid (overall yield 33%). The structures of the synthesized bile acids were confirmed from their proto nuclear magnetic resonance and mass spectral fragmentation patterns.