A Modular Approach to a Library of Semi-Synthetic Fucosylated Chondroitin Sulfate Polysaccharides with Different Sulfation and Fucosylation Patterns

Fucosylated chondroitin sulfate (fCS)—a glycosaminoglycan (GAG) found in sea cucumbers—has recently attracted much attention owing to its biological properties. In particular, a low molecular mass fCS polysaccharide has very recently been suggested as a strong candidate for the development of an antithrombotic drug that would be safer and more effective than heparin. To avoid the use of animal sourced drugs, here we present the chemical transformation of a microbial sourced unsulfated chondroitin polysaccharide into a small library of fucosylated (and sulfated) derivatives thereof. To this aim, a modular approach based on the different combination of only five reactions was employed, with an almost unprecedented polysaccharide branching by O-glycosylation as the key step. The library was differentiated for sulfation patterns and/or positions of the fucose branches, as confirmed by detailed 2D NMR spectroscopic analysis. These semi-synthetic polysaccharides will allow a wider and more accurate structure–activity relationship study with respect to those reported in literature to date.