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 keysynthetic
step represented by the reductive NeO bond cleavage, an unusual double ring opening
afforded the aminol intermediates containing a b-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.