Recent Progress in Preparation and Applications of Oxazino[4,3-a] pyrroloimidazo[5,4-f]benzimidazole (imino)quinone as an Anti-Cancer Agent

Abstract

: The aim of this study is to prepare a novel precursor for the synthesis of imidazo[5,4-f]benzimidazole(imino)quinone. This will target the over-expression of the enzyme NAD(P)H: quinone oxidoreductase (NQO1) in solid tumours. An electron withdrawing group was incorporated into the structure, and the substituted ring size was reduced as this is hypothesised to increase its binding affinity to NQO1. The 2, 5-difluoroaniline was acetylated using acetic anhydride to produce N-(2,5-difluorophenyl) acetamide. The latter underwent selective nitration to produce N-(2,5-difluoro- 4-nitrophenyl) acetamide followed by oxidation using methane sulfonic acid and hydrogen peroxide to give 1,4-difluoro-2,5-dinitrobenzene. The synthesized precursor was achieved by the double nucleophilic aromatic substitution of morpholine and pyrrolidine onto 1,4-difluoro-2,5-dinitrobenzene. The 4-(2,5-dinitro-4-pyrrolid-1-yl) morpholine was successfully synthesized in four synthetic steps. The identity and purity were confirmed using NMR with peaks assigned using proton-fluorine coupling values. Further work is recommended for the developments of this study, additional synthetic steps using the novel precursor need to be carried out to achieve oxazino[4,3-a] pyrroloimidazo[5,4-f] benzimidazole(imino)quinone.