Synthesis of Disaccharides Containing 6-Deoxy-α-L-talose as Potential Heparan Sulfate Mimetics

A 6-deoxy-alpha-L-talopyranoside acceptor was readily prepared from methyl alpha-L-rhamnopyranoside and glycosylated with thiogalactoside donors using NIS/TfOH as the promoter to give good yields of the desired alpha-linked disaccharide (69-90%). Glycosylation with a 2-azido-2-deoxy-D-glucosyl trichloroacetimidate donor was not completely stereoselective (alpha:beta = 6:1), but the desired alpha-linked disaccharide could be isolated in good overall yield (60%) following conversion into its corresponding tribenzoate derivative. The disaccharides were designed to mimic the heparan sulfate (HS) disaccharide GlcN(2S,6S)-IdoA(2S). However, the intermediates readily derived from these disaccharides were not stable to the sulfonation/deacylation conditions required for their conversion into the target HS mimetics.