Hiroshi Susaki

Synthesis of 8-aminooctyl glycopyranosides and of their conjugates with poly(l-glutamic acid) having a 2-(4-hydroxyphenyl) ethylamino group for radiolabeling

Abstract 8-Aminooctyl glycopyranosides of β- d -galactose, β- l -fucose, α- and β- d -xyloses, α- and β- d -mannoses, 2-acetamido-2-deoxy-β- d -mannose, and 2-acetamido-2-deoxy-α- l -fucose were synthesized under Koenigs-Knorr type glycosylation reaction conditions using the corresponding glycopyranosyl halides or 2-azido-2-deoxy-glycopyranosyl halides and N-(8-hydroxyoctyl) phthalimide. Condensation of 8-aminooctyl glycopyranosides of β- d -galactose, β- l -fucose, α- d -xylose, and α- and β- d -mannoses with poly( l -glutamic acid) in the presence of 4-(2-aminoethyl)phenol and 1-(3-dimethylaminopropyl)-3-ethyl- carbodiimide hydrochloride or 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline as a condensation reagent, gave [8-(β- d -galactopyranosyloxy) octylamine]36-[2-(4-hydroxyphenyl)ethylamine]3-poly( l -glutamic acid) conjugate (41), [8-(β- l -fucopyranosyloxy)octylamine], 16-[2-(4-hydroxyphenyl)ethylamine]4-poly( l -glutamic acid) conjugate (42), [8-(α- d -xylopyranosyloxy)octylamine]12-[2-(4-hydroxyphenyl)ethylamine]2-poly( l -glutamic acid) conjugate (43), [8-(α- d -mannopyranosyloxy)octylamine]18-[2-(4-hydroxyphenyl)ethylamine]5-poly( l -glutamic acid) conjugate (44), and [8-(β- d -mannopyranosyloxy)octylamine]27-[2-(4-hydroxyphenyl)ethylamine]2-poly( l -glutamic acid) conjugate (45), respectively. The plasma elimination rates of [125I]-labeled carbohydrate- poly( l -glutamic acid) conjugates bearing 8-(β- d -galactopyranosyloxy)octylami 8-(α- d -mannopyranosyloxy)octylamino residues (41 and 45) after intravenous administration to rats were more rapid than that of [125I] [2-(4-hydroxy-phenyl)ethylamine]5-poly( l -glutamic acid) conjugate (40).