Journal of Lipid Research, Vol 25, 646-650, Copyright © 1984 by Lipid Research, Inc.
Stereospecific synthesis of 3 beta-hydroxylated bile alcohols
B Dayal, DN Greeley, TH Williams, GS Tint and G Salen
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.
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