Synthesis and regioselective ribosylation of 6,7-dichloroimidazo[4,5-b]quinolin-2-one

The polyhalogenated benzimidazole nucleosides 2,5,6-trichloro-1-(beta-D-rib ofuranosyl)benzimidazole (TCRB) and the 2-bromo analogue (BDCRB) were synth esized in our laboratory and established as potent and selective antiviral agents against human cytomegalovirus (HCMV) with a novel mode of action. In an effort to study the behavior of the key substructure of these analogues in a dimensionally stretched-out manner and probe the spatial limitation o f the target enzyme(s), a series of N1- and N3-ribonucleosides of imidazo[4 ,5-b]quinolines were designed as linear dimensional analogues. The nucleosi des 6,7-dichloro-1-(beta-D-ribofuranosyl)imidazo[4,5-b]quinolin-2-one and 6 ,7-dichloro-3-(beta-D-ribofuranosyl)imidazo[4,5-b]quinolin-2-one were selec ted and prepared as the key intermediates in this study. During this study, a novel photoassisted annulation was developed for the synthesis of 6,7-di chloroimidazo[4,5-b]quinolin-2-one, which overcame several problems that we re encountered with the literature annulation method. Regioselective ribosy lations of this heterocycle were developed and gave both the N1 and the N3 isomers in high yield.