Diastereoselective One-Step Synthesis of 2-Keto-3-deoxy-<scp>d</scp>- glycero-<scp>d</scp>-galacto-nononic acid (KDN) Analogues as Templates for the Development of Influenza Drugs

Novel sialic acid scaffolds have great significance in the development of influenza neuraminidase inhibitors. Here the enzymatic synthesis of a wide range of 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN) analogues via aldol addition of pyruvate to D-mannose, D-glucose, D-galactose, 2-deoxy-D-glucose, D-arabinose, L-arabinose and L-rhamnose using a previously unstudied N-acetylneuraminic acid (Neu5Ac) aldolase derived from the bacterium Dyadobacter fermentas was exemplified. Several of the synthesized KDN analogues showed comparable or better inhibitory activity than unstudied Neu5Ac against the mutated influenza neuraminidases (A/California/04/2009 and A/Anhui/1/2005), which both show resistance to Neu5Ac-based neuraminidase inhibitors, demonstrating that these compounds are promising templates for the development of anti-influenza drugs.