SYNTHESIS OF SULFATED AND PHOSPHORYLATED GLYCOPEPTIDES FROM THE CARBOHYDRATE-PROTEIN LINKAGE REGION OF PROTEOGLYCANS

The synthesis of the tetrasaccharide dipeptide beta-D-GlcpA-(1 --> 3)- beta-D-Galp4SO(3)Na-(1 --> 3)-beta-D-Galp-(1 --> 4)-beta-D-Xylp-(1 --> 0)-L-Ser-Gly was achieved by coupling a suitably protected tetrasacch aride trichloroacetimidate, built up from the nonreducing end by the s tepwise addition of monosaccharide units, to the protected dipeptide Z L-Ser-Gly-OBn. Sulfation at 0-4 of the second D-Gal unit and complete deprotection afforded the target molecule in high yield. Its phosphory lated analogue beta-D-GlcpA-(1 -> 3)-beta-D-Galp-(1 --> 3)-beta-D-Galp -(1 --> 4)-beta-D-XyIp2PO(3)Na(2)-(1 --> 0)-L-Ser-Gly was synthesized by coupling a protected trisaccharide trichloroacetimidate to the 2,3- O-isopropylidene derivative of Z-(D-Xyl-)L-Ser-Gly-OBn. Hydrolysis of the O-isopropylidene group, regioselective acetylation at 0-3 of the O -Xyl unit, and phosphorylation at 0-2 followed by complete deprotectio n gave the phosphorylated tetrasaccharide dipeptide in high yield. The se structures are found in the carbohydrate-protein linkage region of several proteoglycans.