Total Synthesis of <i>Pseudomonas aeruginosa</i> 1244 Pilin Glycan via <i>de Novo</i> Synthesis of Pseudaminic Acid

Pseudaminic acid (Pse) is a nonulos­onic acid unique to bacterial species, found as a component of important cell surface glycans and glyco­proteins in various pathogenic species, such as the critical hospital threat <i>Pseudomonas aeruginosa</i>. Herein we present the development of a facile and scalable <i>de novo</i> synthesis of Pse and its functionalized derivatives from easily available Cbz-l-<i>allo</i>-threonine methyl ester (16 steps in 11% yield). The key reactions in our <i>de novo</i> synthesis involve the diastereo­selective glycine thioester isonitrile-based aldol-type reaction to create the 1,3-<i>anti</i>-diamino skeleton, followed by the Fukuyama reduction and the indium-mediated Barbier-type allylation. Moreover, we have studied the glycosyl­ation of the Pse glycosyl donors and identified the structural determinants for its glycosyl­ation diastereo­selectivity, which enabled us to complete the total synthesis of <i>P. aeruginosa</i> 1244 pilin trisaccharide α-5NβOHC<sub>4</sub>­7NFm­Pse-(2→4)-β-Xyl-(1→3)-FucNAc.