Variant synthetic pathway to glucuronic acid-containing di- and trisaccharide thioglycoside building blocks for continued synthesis of Cryptococcus neoformans capsular polysaccharide structures

An alternative pathway to glucuronic acid-containing di- and trisaccharide thioglycoside building blocks, suitable for the synthesis of Cryptococcus neoformans capsular polysaccharide structures, has been developed. As opposed to our earlier synthesis, this approach features the introduction of the glucuronic acid motif at the di- and trisaccharide level through oxidation of a glucose residue. This approach circumvents problems encountered in glycosylations with glucuronic acid donors and benzylation of glucuronic acid-containing derivatives. Selective protection of primary alcohols was obtained at the di- and trisaccharide stage using TBDMS or trityl protecting groups, respectively. After benzylation of the secondary hydroxyl groups and subsequent removal of the TBDMS or trityl group, oxidation of the free primary alcohols to carboxylic acids was performed in high yield using the TEMPO–BAIB reagent mixture, which does not tend to oxidize thioglycosides. The new approach requires a number of extra steps, but has proven to be more reliable and easily reproducible.