Synthesis and Antiviral Properties of Spirocyclic [1,2,3]-Triazolooxazine Nucleosides

An efficient synthesis of spirocyclic triazolooxazine nucleosides is described. This was achieved by the conversion of β‐D‐psicofuranose to the corresponding azido‐derivative, followed by alkylation of the primary alcohol with a range of propargyl bromides, obtained by Sonogashira chemistry. The products of these reactions underwent 1,3‐dipolar addition smoothly to generate the protected spirocyclic adducts. These were easily deprotected to give the corresponding ribose nucleosides. The library of compounds obtained was investigated for its antiviral activity using MHV (mouse hepatitis virus) as a model wherein derivative 3 f showed the most promising activity and tolerability. Taming the ring: Reported herein is the synthesis of a novel class of conformationally restricted nucleoside (see scheme). The synthesis relies on an intramolecular 1,3‐dipolar cycloaddition to generate a class of compounds which have conformational similarities to Ribaviran. Consequently, these systems were tested for their antiviral properties and several were shown to have promising activity against mouse hepatitis virus.