Total Synthesis of <i>Pseudomonas aeruginosa</i> 1244 Pilin Glycan via <i>de Novo</i> Synthesis of Pseudaminic Acid
2017-08-24T00:00:00Z (GMT) by
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.