Synthesis of sulfated octadecyl ribo-oligosaccharides with potent anti-AIDS virus activity by ring-opening polymerization of a 1,4-anhydroribose derivative

The synthesis and anti-AIDS virus activity of sulfated octadecyl ribofuranans with medium-range molecular weights have been investigated. Selective ring-opening polymerization of 1,4-anhydro-2,3-di-O-benzyl-alpha-D-ribopyranose with 10-20 mol% of boron trifluoride etherate as a catalyst in a large amount of dichloromethane gave 2,3-di-O-benzyl-(1-->5)-alpha-D-ribofuranan in good yield. The molecular weight of the benzylated ribofuranan was in the range of 9 X 10(3) to 10 X 10(3). Debenzylation of the polymer followed by acetylation gave peracetylated (1-->5)-alpha-D-ribofuranans. The peracetylated ribofuranans were treated with octadecyl alcohol and a stannic chloride catalyst to afford acetylated ribofuranans having octadecyl groups at the reducing terminal. The molecular weights of the resulting acetylated octadecyl ribofuranans were below 9 X 10(3). Sulfation of the deacetylated octadecyl ribofuranans by piperidine-N-sulfonic acid in dry Me(2)SO gave sulfated octadecyl ribofuranans with molecular weights of 3 X 10(3) to 9 X 10(3) and sulfur contents of 13.0-16.2%. The sulfated octadecyl ribofuranans had potent anti-AIDS virus activity, EC(50) = 0.6-2.5 mu g/mL (a standard curdlan sulfate showed EC(50) = 0.43 mu g/mL), and low anticoagulant activity, 4-17 units/mg (a standard dextran sulfate, 22.7 unit/mg). Structural analysis of the ribofuranans was performed by NMR at 400 and 600 MHz.