Bile alcohol glucuronides: regioselective O-glucuronidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol

Abstract

A facile and regiocontrolled procedure for the preparation of 5-beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol-3-O-beta-D-glucuronide and its corresponding C-26 analogue is described. The method involves direct coupling of bile alcohols, namely, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol to methyl (tetra-O-acetyl-beta-D-glucopyranuronate) in the presence of a Lewis acid, tin(IV) chloride, in dichloromethane. The resulting anomeric pairs of 1,2-trans- and 1,2-cis-glucuronides of tetrols were resolved by analytical and preparative thin-layer chromatography, and their identities were established by high-resolution 1H NMR spectroscopy and by chemical-ionization and fast-atom-bombardment mass spectrometry. The method described has a practical advantage over the traditional two-step synthesis involving bromides as it is more efficient and uses inexpensive and less toxic materials. It is suggested that these compounds will be useful for studying permeability of the blood-brain barrier in cerebrotendinous xanthomatosis (CTX).