Stereospecific synthesis of 3 beta-hydroxylated bile alcohols

• Published in: Journal of lipid research Vol. 25; no. 6; pp. 646 - 650
• Main Authors: Dayal, B, Greeley, D N, Williams, T H, Tint, G S, Salen, G
• Format: Journal Article
• Language: English
• Published: United States Elsevier 01.06.1984
• Subjects: Bile Acids and Salts; Cholestanols - chemical synthesis; Magnetic Resonance Spectroscopy; Stereoisomerism
• ISSN: 0022-2275
• DOI: 10.1016/S0022-2275(20)37778-6

This paper describes the synthesis of 5 beta-cholestane-3 beta, 7 alpha,25-triol and 5 beta-cholestane-3 beta, 7 alpha, 12 alpha, 25-tetrol from their corresponding 3 alpha-analogs. The method consists of refluxing a mixture of a steroid alcohol, triphenylphosphine, and diethyl azodicarboxylate in benzene solution with an acid such as formic acid. The sterically pure ester (3 beta-formate) so formed after saponification then allows an easy access to the epimer of the starting alcohol. Differentiation of these 3 beta-hydroxy bile alcohols from their corresponding 3 alpha-epimeric analogs was made possible on the basis of proton, 13C-NMR, and mass spectra as well as chromatographic mobility. Steric requirements of sterols and nucleophilicity of attacking acidic components played an important role for the success of this synthesis. Only equatorial hydroxyl groups in these bile alcohols reacted under mild conditions and epimerization, as well as protection of the alcoholic group, was achieved in one step. Formic acid was the acid of choice since the axial formate ester formed is sufficiently reactive to be hydrolyzed (KHCO3/aq X MeOH) under mild conditions.