Saccharide Thiols for the Synthesis of S-Linked Glycosaminoglycan Analogues

Glycosaminoglycans (GAGs) are an important group of biomolecules and are unbranched polysaccharides consisting of repeating disaccharide moieties. One GAG, heparin, is polysulfated with alternating D-glucosamino and either D-glucuronic or L-iduronic acid units and is used as an anticoagulant drug.[1] As part of our work on heparin analogues in which the disaccharide units are S-linked rather than O-linked, we are attempting to synthesize the disaccharide thiol 5. (see Scheme below). The donor 1 is synthesized starting from glucose pentaacetate and the acceptor 2 from glucosamine hydrochloride The disaccharide 3 obtained from the glycosylation reaction between 1 and 2 has been subjected to multistep manipulations to give 4, a possible precursor to the desired thiol 5.