Chemoenzymatic synthesis of heparin oligosaccharides

Abstract

Chemoenzymatic synthetic methods can provide efficient synthetic routes to heparin-derived oligosaccharides. By combining techniques from traditional organic synthesis and enzymatic catalysis, synthetic routes can be made shorter and with greater yields. One of these techniques is fluorous separations. Tagging an oligosaccharide with a fluorous group and using fluorous affinity chromatography can make the purifications of enzymatic reactions easy. Another technique is the use of unnatural substrates for enzymatic reaction. Several unnatural glycosylation acceptors have been chemically synthesized, and their use as enzymatic substrates in various conditions is explored. Finally, chemoenzymatic techniques have been applied to a synthetic scheme resulting in the pentasaccharide anticoagulant fondaparinux. Several methods for the purification of di-, tri- and tetrasaccharide enzymatic products have been examined and discussed.