Exploring the Interactions of Unsaturated Glucuronides with Influenza Virus Sialidase

Abstract

A series of C3 O-functionalized 2-acetamido-2-deoxy-?4-߭D-glucuronides were synthesized to explore noncharge interactions in subsite 2 of the in?uenza 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 in?uenza virus sialidase at a sub-占level; the introduction of small alkyl substituents or an acetyl group at C3 is also tolerated.