Synthesis, properties, and hepatic metabolism of strongly fluorescent fluorodipyrrinones

Abstract

From non-fluorescent 8-H fluorophenyldipyrrinones, highly fluorescent (ϕF 0.4–0.6) analogs have been synthesized by reaction with 1,1′-carbonyldiimidazole to bridge the dipyrrinone nitrogens and form an N,N′-carbonyldipyrrinone (3H,5H-dipyrrolo[1,2-c:2′,1′-f]pyrimidine-3,5-dione). Amphiphilic, water-soluble 8-sulfonic acid derivatives are then obtained by reaction with concd H2SO4. The resulting fluorinated and sulfonated N,N′-carbonyl-bridged dipyrrinones, isolated as their sodium salts, are potential cholephilic fluorescence and 19F MRI imaging agents for use in probing liver and biliary metabolism. After intravenous injection in the rat they were excreted rapidly and largely unchanged in bile. 19F NMR spectroscopy of a pentafluorophenyl-tosylpyrrolinone synthetic precursor exhibited rarely seen diastereotopicity.