Synthesis of a novel 'smart' bifunctional chelating agent 1-(2-[β,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4- aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10- tetraazacyclododecane (Gal-PA-DO3A-NH_2) and its Gd(Ⅲ) complex

摘要

A new synthetic pathway to 1-(2-[β,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyI)-4,10-bis(carb-oxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH_2) and 1 -(2-[β,D-galactopyranosyloxy]ethyl)-4,7,10-tris(carboxy-methyl)-1, 4,7,10-tetraazacyclododecane (Gal-DO3A) chelating agents was developed involving full hydroxyl- and carboxyl-group protection in precursors to product. Two sequences of cyclen-N-functionalisation were subsequently investigated, one successfully, towards synthesis of the novel 'smart' bifunctional Gal-PA-DO3A-NH_2 chelate. The longitudinal proton relaxivities of the neutral [Gd-(Gal-PA-DO3A-NH_2)] and [Gd-(Gal-DO3A)] complexes were increased by 28% and 37% in the presence of β-galac tosidase, respectively.