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

Abstract

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-α- 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)-α- d-ribofuranan in good yield. The molecular weight of the benzylated ribofuranan was in the range of 9 × 10 3 to 10 × 10 3. Debenzylation of the polymer followed by acetylation gave peracetylated (1 → 5)-α- 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 × 10 3. Sulfation of the deacetylated octadecyl ribofuranans by piperidine-N-sulfonic acid in dry Me 2SO gave sulfated octadecyl ribofuranans with molecular weights of 3 × 10 3 to 9 × 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 μg/mL (a standard curdlan sulfate showed EC 50 = 0.43 μg/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.