Synthesis and evaluation of putative oxocarbenium intermediate mimic in the KDO8P synthase-catalyzed reaction as a tool for the design of potent inhibitors for lipopolysaccharide biosynthesis

The new amino phosphonate 4, which mimics the ionic and steric properties of putative oxocarbenium intermediate 3, was synthesized from -mannose and evaluated as inhibitor of Kdo8P synthase. It was found that 4 is the most potent inhibitor of the enzyme yet tested, with a Ki value of 3.3 μM.