The first synthesis of azanonaborane-containing sugars, possible boron carriers for neutron capture therapy

Abstract

A novel class of boron containing sugars is described. They were synthesized in acceptable yields from readily available starting materials. Reaction of (4-aminobutylamine)-(N-aminobutyl)azanonaborane(11) [H₂N(CH₂)₄H₂NB₈H₁₁NH(CH₂)₄NH₂] with acetobromo-α-D-glucose or acetobromo-α-D-galactose in acetonitrile followed by hydrolysis with sodium methoxide afforded (4-α-glucopyranosylaminobutylamine)-(N-α-glucopyranosylaminobutyl)azanonaborane(11) or (4-α-galactopyranosylaminobutylamine)-(N-α-galactopyranosylaminobutyl)azanonaborane(11) in 65% and 63% yields, respectively. In a one step process, treatment of a B₈N cluster with D-ribose in methanol in the presence of a catalytic amount of glacial acetic acid gave (4-α-ribofuranosylaminobutylamine)-(N-α-ribofuranosylaminobutyl)azanonaborane(11) in 78% yield. The connection of monosaccharide units to the azanonaborane cluster enhances the stability and the water solubility of the resulting compounds, which are considered important factors for boron neutron capture therapy (BNCT) delivery agents. The in vitro toxicity test using B16 melanoma cells showed that azanonaborane clusters containing sugar are not toxic even at boron concentrations of 3 mM, whereas (4-aminobutylamine)-(N-aminobutyl)azanonaborane(11) has an LD₅₀ of about 700 μM. Results obtained from these studies may provide a more definitive answer as to the potential usefulness of these compounds for BNCT.