Synthesis of functionalized cyclohexenephosphonates and their inhibitory activity towards bacterial sialidases

We have synthesized a series of cyclohexenephosphonates derived from d- and l-xylose, designed as core structures for the development of high affinity mimics of sialic acid and of the sialidase reaction transition state. Extension of our syntheses to both xylose enantiomers has given us access to two series of cyclohexenephosphonates with regioisomeric double bonds. We have demonstrated the selective functionalization of the hydroxyl groups towards introduction of a glycerol side chain mimic and immobilization via a silyl linker. The inhibitory activity of a selected set of compounds towards three bacterial sialidases has been tested and moderate activity was found.