Synthesis of 2,6,7-Trichloro-1-(β-d-ribofuranosyl)naphtho[2,3-d]imidazole: A Linear Dimensional Analogue of the Antiviral Agent TCRB

Abstract

Human cytomegalovirus (HCMV) remains a significant clinical problem in neonates and immunocompromised individuals such as those undergoing transplantation as well as individuals with acquired immune deficiency syndrome (AIDS). Recently in our laboratory, 2,5,6-trichloro-1-(β-d-ribofuranosyl)benzimidazole (TCRB, 1a) and 2-bromo-5,6-dichloro-1-(β-d-ribofuranosyl)benzimidazole (BDCRB, 1b) were found to have better activities in cell culture studies against HCMV than the clinically used agents ganciclovir and foscarnet. These benzimidazole compounds appear to act by a unique mechanism. However, as the biological target of TCRB and BDCRB has not been completely identified, 2,6,7-trichloro-1-(β-d-ribofuranosyl)naphtho[2,3-d]imidazole (2) was designed as a linear dimensional analogue of TCRB for a study on the spatial limitation of the binding site in the target enzyme. In the synthesis, a convenient route was developed for the synthesis of 2-substituted 6,7-dichloronaphtho[2,3-d]imidazoles involving a Diels−Ald...