Reliable Chemical Synthesis of UDP-3-<i>O</i>-[(<i>R</i>)-3-Hydroxydecanoyl]-GlcNAc: The Native Substrate of <i>Pseudomonas aeruginosa</i> LpxC

Herein, we describe a reliable and efficient approach for the first chemical synthesis of biologically significant and complex 3-<i>O</i>-(<i>R</i>-3-hydroxydecanoyl) modified uridine diphosphate <i>N</i>-acetylglucosamine that is the native substrate of LpxC involved in the biosynthesis of the cell wall of <i>Pseudomonas aeruginosa</i>. The synthetic protocol provides a successful example for the reliable preparation of modified nucleoside diphosphate sugar, which features judiciously selected protecting groups, the formation of pyrophosphate linkage with 5'-phosphate nucleoside as nucleophile, and the straightforward purification process.