SYNTHESIS OF β-Δ-GalNAc4,6-diS(1-4)[α-L-Fuc2,4-diS(1-3)]β-Δ-GlcA, A NOVEL TRISACCHARIDE UNIT OF SEA CUCUMBER

Body wall of the sea cucumbers often contain chondroitin sulfate (CS) like acidic polysaccharides which have CS backbone with sulfated fucoses as branches [1]. These acidic polysaccharides show anticoagulant activity [2] even via oral dose different from heparin. However the relationship between the biological activity and the structural domain is still obscure. These novel acidic polysaccharides are promising as a new type of drug. These facts prompted us to synthesize the novel acidic oligosaccharide to elucidate the problems. Here we report the first synthesis of the representative repeating CS disaccharide unit having sulfated fucose at O-3 of GlcA residue as a 4-methoxyphenyl glycoside; β-D-GalNAc4,6-diS(1-4)[α-L-Fuc2,4-diS(1-3)]β-D-GlcA-OMP. We prepared a suitably protected GalN₃-GlcA disaccharide moiety based on the established procedures of the CS-synthesis with some arranges. The liberated OH-3 of the GlcA residue was stereoselectively fucosylated. The target trisaccharide was finally obtained after sulfation at four OH groups, hydrogenolysis to remove benzyl ethers also to reduce the azide to amine, N-acetylation and final saponification in good yields. The final product was well assigned as the desired trisaccharide by ¹H-NMR.

References

[2] R. J. C. Fonseca and P. A. S. Mourão, Thromb. Haemost., 96, 822-829 (2006).