Inter vs. intraglycosidic acetal linkages control sulfation pattern in semi-synthetic chondroitin sulfate

tMicrobial-sourced unsulfated chondroitin could be converted into chondroitin sulfate (CS) polysaccha-ride by a multi-step strategy relying upon benzylidenation and acetylation reactions as key-steps for itsregioselective protection. By conducting the two reactions one- or two-pots, CSs with different sulfationpatterns could be obtained at the end of the semi-synthesis. In particular, a CS polysaccharide possess-ing sulfate groups randomly distributed between positions 4 and 6 of N-acetyl-galactosamine (GalNAc)units could be obtained through the two-pots route, whereas the one-pot pathway allowed an additionalsulfation at position 3 of some glucuronic acid (GlcA) units. This difference was ascribed to the stabi-lization of a labile interglycosidic benzylidene acetal involving positions O-3 and O-6 of some GlcA andGalNAc, respectively, when the benzylidene-acetylation reactions were conducted in a one-pot fashion.Isolation and characterization of a polysaccharide intermediate showing interglycosidic acetal moietieswas accomplished.