Exploring the Interactions of Unsaturated Glucuronides with Influenza Virus Sialidase

A series of C3 <i>O</i>-functionalized 2-acetamido-2-deoxy-Δ⁴-β-d-glucuronides were synthesized to explore noncharge interactions in subsite 2 of the influenza virus sialidase active site. In complex with A/N8 sialidase, the parent compound (C3 OH) inverts its solution conformation to bind with all substituents well positioned in the active site. The parent compound inhibits influenza virus sialidase at a sub-μM level; the introduction of small alkyl substituents or an acetyl group at C3 is also tolerated