Synthesis of sulfonated amino-polysaccharides having anti-HIV and blood anticoagulant activities

Abstract

Sulfonated 3-amino-3-deoxy-( 1 → 6)- α- d-allopyranans were synthesized to elucidate the relationship between structure and such specific biological activities as anti-HIV and blood anticoagulant activities. Ring-opening copolymerization of 1,6-anhydro-3-azido-2,4-di- O-benzyl-3-deoxy- β- d-allopyranose 1 with 1,6-anhydro- 2,3,4-tri- O-benzyl- β- d-allopyranose 2 with PF 5 catalyst gave copolymers having various proportions of the 1 unit. 13C NMR spectroscopy showed the resulting copolymers to have α-( 1 → 6)-stereoregularity, and the monomer reactivity ratios were calculated to be r 1 =0.92 and r 2 =1.11 by the Kelen–Tüdös method. Reduction of the azido groups and subsequent debenzylation of the copolymers afforded new amino-polysaccharides consisting of 3-amino-3-deoxy-allose and allose units. Sulfonation of 3-amino-3-deoxy-( 1 → 6)- α- d-allopyranan and copolysaccharides consisting of 3-amino-allose and allose or glucose units was performed with piperidine- N-sulfonic acid to give polysaccharides containing sulfoamido and sulfonate groups in good yields. The sulfoamido-copolysaccharides containing of 3-amino-3-deoxy-allose and glucose units exhibited high anti-HIV activities manifested by the 50% protecting concentration (EC 50) of 0.2–0.5 mg/mL and low cytotoxicity shown by a 50% cytotoxic concentration (CC 50) of >1000 μg/mL. The sulfoamido-copolysaccharides containing 3-amino-allose and allose units had somewhat lower anti-HIV activities (EC 50=0.8–0.9 μg/mL) and slightly higher cytotoxicities (CC 50=740∼797 μg/mL). In addition, it was found that the blood anticoagulant activity increased, with increasing proportion of the amino-allose unit, from 30 to 58 unit/mg (standard dextran sulfate, 22.7 unit/mg). These results suggest that the sulfonated 3-amino-3-deoxyallose unit plays important roles on both anti-HIV and blood anticoagulant activities.