Synthesis and molecular modeling of novel dihydroxycyclopentane-carbonitrile nor-nucleosides by bromonitrile oxide 1,3-dipolar cycloaddition

The regioisomeric cycloadducts of the bromonitrile oxide to the N-benzoyl-2,3-oxazanorborn-5-ene were easily prepared and elaborated into a novel class of uracil nor-nucleoside derivatives. In the key-synthetic step represented by the reductive N–O bond cleavage, an unusual double ring opening afforded the aminol intermediates containing a β-hydroxynitrile structure. By adapting known protocols, the aminols entered the linear construction of uracil rings. These novel nucleosides were found structurally similar to a potent antiviral compound, Brivudin, and molecular modeling and docking allowed to select one of the two regioisomeric structures as promising candidate for antiviral tests, due to the nice level of binding with the Thymidine Kinase, the enzyme involved in virus replication.