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Total Synthesis of Pseudomonas aeruginosa 1244 Pilin Glycan via de Novo Synthesis of Pseudaminic Acid
journal contribution
posted on 2017-08-24, 00:00 authored by Han Liu, Yanfeng Zhang, Ruohan Wei, Gloria Andolina, Xuechen LiPseudaminic 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 Pseudomonas aeruginosa. Herein we
present the development of a facile and scalable de novo synthesis of Pse and its functionalized derivatives from easily
available Cbz-l-allo-threonine methyl ester
(16 steps in 11% yield). The key reactions in our de novo synthesis involve the diastereoselective glycine thioester
isonitrile-based aldol-type reaction to create the 1,3-anti-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 P. aeruginosa 1244 pilin trisaccharide α-5NβOHC47NFmPse-(2→4)-β-Xyl-(1→3)-FucNAc.