Synthesis of Novel Acyclic Nucleoside and Acyclic Nucleoside Phosphonate Analogues of a Ring-Expanded ("Fat") Nucleobase Containing the Imidazo[4,5-e][1,3]diazepine Ring System.

A number of acyclic nucleosides and nucleoside phosphonates have exhibited potent antiviral activities in recent years, and many of them have been approved by U.S. Food and Drug Administration (FDA) for a variety of viral infections. These include, but are not limited to, Acyclovir (I) for herpes simplex virus (HSV I and HSV II), Ganciclovir (II) for human cytomegalovirus (HCMV), Penciclovir (III) and Adefovir (PMEA) (IV) for hepatitis B virus (HBV). We have recently reported the synthesis and potent anti-HBV activity of a ring-expanded ("fat") nucleoside (V). We now report the synthesis of an acyclic nucleoside analogue (VI) as well as an acyclic nucleoside phosphonate analogue (VII) of the "fat" nucleoside V.