Synthesis of a carbocyclic sialic acid analogue for the inhibition of influenza virus neuraminidase

The influenza virus neuraminidase (NA) is essential for viral infection and offers a potential target for antiviral drug development. We prepared a carbocyclic sialic acid analogue, potentially able to inhibit NA. Its structure is an analogue of the transition-state of the reaction catalysed by NA. As starting material, quinic acid was selected owing to its ready availability and its stereochemical feature suitable for the target structure. The quinic acid was first converted in the shikimic acid; then two of the three hydroxyl functions of this product were selectively functionalised to obtain the target molecule (3 R,4 S,5 R)-4-acetamido-3-guanidino-5-hydroxycyclohex-1-ene-1-carboxylic acid. A carbocyclic sialic acid analogue 17, potentially able to inhibit neuraminidase (NA), was prepared. Its structure in an analogue of the transition state of the reaction catalysed by NA.