Strategies in Synthesis of Heparin/Heparan Sulfate Oligosaccharides: 2000-Present

Heparin and heparan sulfate are members of the glycosaminoglycan family that are involved in a multitude of biological processes. The great interests in the anticoagulant properties of heparin have stimulated major advances in synthetic strategies toward clinically effective analogues, as demonstrated importantly by the approval of the fully synthetic pentasaccharide fragment, termed fondaparinux (Arixtra®), of the heparin macromolecule for treatment of deep-vein thrombosis. Given the highly complex nature of heparin and heparan sulfate, the chemical synthesis of their components is a challenging endeavor. In the past decade, multiple approaches have been developed to improve the overall synthetic efficiency. New strategies have emerged that can generate libraries of oligosaccharide components of heparin and heparan sulfate. This article discusses recent developments in the assembly of heparin and heparan sulfate oligosaccharides and the associated challenges in their synthesis.