Chemical Synthesis of Fucosylated Chondroitin Sulfate Oligosaccharides.

Fucosylated chondroitin sulfates (FuCSs) are a unique type of polysaccharides occurring in sea cucumber that show a variety of biological activities. In particular, well-defined FuCS oligosaccharides, consisting of a trisaccharide repeating unit of β-d-GalNAc(4,6-diS)-(1→4)-[α-l-Fuc(2,4-diS)-(1→3)]-β-d-GlcUA, display potent anticoagulant activity via selective inhibition of the intrinsic tenase, which could be developed into anticoagulant drugs without bleeding risk. Herein, we report an effective approach to the synthesis of FuCS oligosaccharides, as demonstrated by the successful elaboration of FuCS tri-, hexa-, and nonasaccharides. The syntheses employ an orthogonally protected trisaccharide as a pivotal building block that can be readily converted into the donor and acceptor for glycosidic coupling. In addition, the internal patterns of protecting groups, involving N-trichloroacetyl for N-acetyl group, benzylidene and benzyl groups for sulfonated hydroxyl groups, and benzoyl and methyl esters for free hydroxyl and carboxylic acid, respectively, ensure stereoselective formation of the glycosidic linkages and sequential transformation into the desired FuCS oligosaccharides.