Adverse effects of alkali and acid on the anticoagulant potency of heparin, evaluated with methyl 2-deoxy-2-sulf- amino-α-d-glucopyranoside 3-sulfate as a model compound

Abstract A variety of chemical modifications can induce a reduction in the anticoagulant activity of heparin. Among such modifications are the removal in alkaline solution of the 2- O -sulfonate group of α- l -idopyranosyluronic acid 2-sulfate residues ( 1 ) and, in a weakly acidic medium, of the N -sulfonate group of residues of 2-deoxy-2-sulfamino-α- d -glucopyranose 6-sulfate ( 2 ). This study examined the possibility that the losses in anticoagulant potency are related to a concomitant removal of the 3- O -sulfonate group of residues of 2-deoxy-2-sulfamino-α- d -glucopyranose 3,6-disulfate ( 6 ) in the AT-III binding site. It entailed a synthesis of methyl 2-deoxy-2-sulfamino-α- d -glucopyranoside 3-sulfate ( 7 ), as a model compound that was subjected to both the strongly alkaline and weakly acidic conditions appropriate for the modification of residues 1 and 2 , respectively. The 3-sulfate group of 7 was found to be highly stable in both environments. This indicated that the adverse effects that these conditions have on the anticoagulant properties of heparin are not specifically associated with the 3-sulfate substituent of residues of 6 in the polymer.