Synthesis of bile acid 24-acyl glucuronides

The synthesis of acyl glucuronides of common bile acids is described. By means of the Mitsunobu reaction employing diethylazodicarboxylate and triphenylphosphine, bile acids were condensed through the inherent C-24 carboxy group with benzyl 2,3,4-tri-O-benzyl-D-glucopyranuronate, which was prepared from 1-O-methyl-alpha-D-glucose. The separation and purification of the beta-anomers at the anomeric position of the sugar moiety were attained by preparative thin-layer chromatography and/or high-performance liquid chromatography on a column packed with phenyl-bonded silica using H2O-MeOH as a mobile phase. The removal of the benzyl group on the sugar moiety was achieved by catalytic hydrogenation with 10% palladium on carbon to yield the desired acyl glucuronides of bile acids. The structures of these acyl glucuronides were confirmed by proton nuclear magnetic resonance spectral properties.