ChemInform Abstract: 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-ribofuranosyl)benzimidazole (TCRB) and the 2-bromo analogue (BDCRB) were synthesized 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 of the target enzyme(s), a series of N1- and N3-ribonucleosides of imidazo[4,5-b]quinolines were designed as linear dimensional analogues. The nucleosides 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 selected and prepared as the key intermediates in this study. During this study, a novel photoassisted annulation was developed for the synthesis of 6,7-dichloroimidazo[4,5-b]quinolin-2-one, which overcame several problems that were encountered with the literature annulation method. Regioselective ribosylations of this heterocycle were developed and gave both the N1 and the N3 isomers in high yield.