SYNTHETIC STUDIES ON SELECTIN LIGANDS INHIBITORS - SYNTHESIS AND BIOLOGICAL EVALUATION OF SULFATED AND PHOSPHORYLATED BETA-D-GALACTOPYRANOSIDES AND LACTOPYRANOSIDES CONTAINING FATTY-ALKYL RESIDUES OF DIFFERENTCARBON-CHAIN LENGTHS/

To investigate the biological selectin-ligand interactions, fourteen s ulfated and eight phosphorylated beta-D-galacto-and lactopyranosides c ontaining branched fatty-alkyl residues in place of the ceramide have been synthesized. Regioselective sulfation of the parent glycolipids t hrough the dibutylstannylene acetal with a certain amount of sulfur tr ioxide-trimethylamine complex produced the target sulfated glycolipids , while stepwise phosphorylation by treatment of the properly protecte d diol with dibenzyloxy(diisopropylamino)phosphine gave the phosphoryl ated glycolipids. The synthetic glycolipids showed an interesting mode of inhibition of the binding of HL-60 cells to immobilized P-, L- and E-selectins during in vitro experiments. In addition, using computer modeling techniques, we examined the molecular basis for the ligand-se lectin complex formation. These glycolipids may be useful as therapeut ic agents against selectin-dependent inflammation.