A convenient procedure for the synthesis of 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,23-tetrol (23R and 23S) and 24-nor-5 beta-cholestane-3 alpha,7 alpha,12alpha,26-tetrol (25R and 25S) starting from 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol was developed.
Dehydration of 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha, 25-tetrol with
glacial acetic acid and
acetic anhydride yielded a mixture of 24-nor-5 beta-cholest-23-ene-3 alpha,7 alpha,12 alpha-triol and the corresponding delta 25 compound. Hydroboration and oxidation of the mixture of unsaturated nor-triols resulted in the formation of 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,23-tetrols (23R and 23S) and 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,26-tetrols (25R and 25S). In addition, smaller amounts of 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,22 xi-tetrol and 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol were also obtained. The C26
bile alcohols epimeric at C-23 and C-25 were resolved by analytical and preparative TLC and characterized by gas-liquid chromatography and mass spectrometry. Provisional assignment of the configurations of the C-23 and C-25
hydroxyl groups were made on the basis of molecular rotation differences. These C26
alcohols will be used to test the stereospecificity of the hepatic
enzymes that promote oxidation of the
cholesterol side chain.