Synthesis and Anti-HIV Activity of Sulfated Polysaccharides Containing Acetamido Groups.

Abstract

A series of stereoregular azido group-containing copolymers such as poly [3-azido-2-O-t-butyldimethylsilyl-3-deoxy-(1→5)-α-D-xylofuranose-co-2, 3-di-O-t-butyldimethylsilyl-(1→5)-α-D-ribofuranose] [copoly (A3ASX-ADSR)] were synthesized by selective ring-opening polymerization of 1, 4-anhydro-3-azido-2-O-t-butyldimethylsilyl-3-deoxy-α-D-xylopyranose (A3ASX) and 1, 4-anhydro-2, 3-di-O-t-butyldimethylsilyl-α-D-ribopyranose (ADSR) with BF3•OEt2 catalyst. The number-average molecular weights (_??_n) were in a range of 3.5×104_??_4.2×104. The optical rotations ([α] D) increased from +119°to+143° with increasing mole fraction of the xylofuranosidic units in the copolymers from 30% to 78%.Reduction of the azido group in the copolymer into an amino group, acetylation of the amino group into an acetamido group, and removal of the t-butyldimethylsilyl group afforded poly [3-acetamido-3-deoxy-(1→5)-α-D-xylofuranose-co-(1→5)-α-D-ribofuranose] [copoly (A3AAdX-R)] with _??_n 9.0×103 and [α] D of +150.8°. Sulfation of the 3AAdXF and copoly (A3AAdX-R) produced a sulfated 3-acetamido-3-deoxy-(1→5)-α-D-xylofuranan with _??_n of 17.1×103, and a sulfated poly _??_3-acetamido-3-deoxy-(1→5)-α-D-xylofuranose-co-(1→5)-α-D-ribofuranose_??_ with _??_n of 10.9×103. The degrees of sulfation of homo- and co-polymers were 0.72 and 1.03, respectively. The four kinds of sulfated acetamido group-containing polypentoses exhibited medium-to-high anti-HIV (human immunodeficiency virus) activities in the range of EC50 of from 0.42μg/mL to 62.86μg/mL, while they showed low anticoagulant activities in the range of 0 to 6unit/mg.