From Polymer to Size-Defined Oligomers: An Expeditious Route for the Preparation of Chondroitin Oligosaccharides

摘要

Chondroitin sulfates are structurally complex, polyanionic, microheterogeneous, linear polysaccharides belonging to the glycosaminoglycan family. They are ubiquitous components of the extracellular matrix of all connective tissues, but are also found on mammalian cell surfaces and in neural tissues.[1] They are copolymers made of dimeric units composed of D-glucuronic acid (GlcA) and 2-acetamido-2-deoxy-D-galactose (GalNAc) arranged in the sequence [4)--D-GlcA-(13)--D-GalNAc-(1]n, and contain on average one sulfate group per disaccharide unit, but other types with sulfate(s) at various positions are also known. These sulfation patterns give rise to numerous biologically important functions, such as cell-cell recognition,[2] brain development and regeneration,[3] or binding to selectins,[4] and many other that are not completely deciphered at the molecular level. Unfortunately, structurally defined oligosaccharide fragments of chondroitin and its sulfo forms are not easily prepared, even though they are in great demand. Thus, rapid and efficient methods for the preparation of chondroitin sulfate oligomers are critical to advance our understanding of this important class of biomolecules. Synthetic approaches should ideally provide ready access and involve a small number of steps. Several syntheses of chondroitin sulfate oligosaccharides have recently been reported,[5] all starting from monomeric units. Since D-GalNAc is a rare and somewhat expensive sugar, its derivatives have been generally prepared by long routes. In a continued effort to try to reduce the number of transformations in a multistep procedure, we turned our attention towards the possible chemical hydrolysis of chondroitin sulfate polymers. These compounds are abundant and readily available, and were formerly mainly obtained from bovine cartilage. However, the discovery of bovine spongiform encephalopathy has meant that they cannot be used anymore, at least for medical purposes. Commercial products are now obtained from cartilage of marine origin (shark, skate), and they should constitute an attractive starting material for organic chemists.