Synthesis and anti-HIV activity of sulfated polysaccharides containing acetamido groups

A series of stereoregular azido group-containing copolymers such as poly [3-azido-2-O-t-butyldimethylsilyl-3-deoxy- (1-->5) -alpha-D-xylofuranose-co-2,3-di-O-t-butyldimethylsilyl- (1 --> 5)-alpha-D-ribofuranose] [copoly (A3ASX-ADSR)] were synthesized by selective ring-opening polymerization of 1,4-anhydro-3-azido-2-O-t-butyldimethylsilyl-3-deoxy-alpha-D-xylopyranose (A3ASX) and 1,4-anhydro-2,3-di-O-t-butyldimethylsilyl- alpha-D-ribopyranose (ADSR) with BF3. OEt2 catalyst. The number-average molecular weights (M) over bar n) were in a range of 3.5 x 10(4) similar to 4.2 x 10(4). The optical rotations ([alpha]D) increased from +119 degrees to +143 degrees 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)alpha-D-xylofuranose-co- (1-->5) -alpha-D-ribofuranose] [copoly(A3AAdX-R)] with (M) over bar n 9.0 x 10(8) and [alpha]D of + 150.8 degrees. Sulfation of the 3AAdXF and copoly(A3AAdX-R) produced a sulfated 3-acetamido-3-deoxy- (1-->5)-alpha-D-xylofuranan with (M) over bar n of 17.1 x 10(3), and a sulfated poly[3-acetamido-3-deoxy- (1-->5) alpha-D-xylofuranose-co-(1-->5) -alpha-D-ribofuranose] with (M) over bar n of 10.9 x 10(3). 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 0.42 mu g/mL to 62.86 mu g/mL, while they showed low anticoagulant activities in the range of 0 to 6 unit/mg.