An efficient, stereocontrolled, and highly divergent approach for the preparation of oligomers of chondroitin sulfate (CS) A, C, D, E, K, L, and M variants, starting from a single precursor easily obtained by semisynthesis from abundant natural polymer is reported for the first time. Common intermediates were designed that allowed the straightforward construction of O-sulfonated species either on the D-galactosamine unit (CS-A, -C, and -E) or on both D-glucuronic acid and D-galactosamine units (CS-D and CS-K, -L, and -M). This strategy represents a successful improvement and brings a definitive answer toward the synthesis of such complex molecules with numerous relevant biological functions.

Controlled acid hydrolysis of polymeric chondroitin sulfate of bovine origin afforded in good yield a basic disaccharide fragment that was used for the first time as a starting material for the expeditious preparation of a set of building blocks that in turn act as versatile synthons for the efficient and stereocontrolled construction of a collection of size-defined chondroitin oligomers (from di- to octasaccharides). This step economy process allows their preparation as reducing species, fitted with a fluorophore, or as biotinylated conjugates; all useful tools for the preparation of microarrays, or as probes for the study of the biosynthesis of chondroitin sulfate.