Synthesis and biological evaluation of 2-amino-2-deoxy- and 6-amino-6-deoxy-cyclomaltoheptaose polysulfates as synergists for angiogenesis inhibition

Abstract

2-Amino-2-deoxy-cyclomaltoheptaose was prepared from β-cyclodextrin perbenzoate [heptakis(2,3,6-tri- O-benzoyl)cyclomaltoheptaose] by a series of reactions including selective de- O-benzoylation at C-2 of one of the perbenzoylated d-glucopyranosyl moieties, oxidation to the 2-ulose derivative, oxime formation, and reduction to the 2-amino-2-deoxy- d-glucose moiety. This compound and 6-amino-6-deoxycyclomaltoheptaose accessible from β-cyclodextrin through the known procedure were sulfated to give polysulfated aminocyclomaltoheptaose derivatives ( 3, 5). Employing β-cyclodextrin polysulfate as a reference compound, the synergistic effects of 3 and 5 for cortexolone on angiogenesis inhibitory activity were examined by rabbit-corneal micropocket assay system. In contrast to the significant anti-angiogenesis activity of the β-cyclodextrin polysulfate-cortexolone pair, neither 3 nor 5 showed any cooperative activity with cortexolone in the inhibition of basic FGF-induced angiogenesis.