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.