Total Synthesis of the Repeating Units of Highly Functionalized O-Antigens of Pseudomonas aeruginosa ATCC 27577, O10, and O19

Abstract

The first total synthesis of the repeating units of the O-antigens of Pseudomonas aeruginosa ATCC 27577, O10, and O19 was achieved via a linear glycosylation strategy. This also represents the first synthesis of an oligosaccharide containing an α-linked N-acetyl-l-galactosaminuronic acid (l-GalpNAcA) unit. All of the glycosyl linkages, including three challenging 1,2-cis-glycosidic bonds of amino sugars, were effectively constructed with high to exclusive stereoselectivity, while orthogonal protection tactics were employed to facilitate regioselective glycosylations and the introduction of a variety of functionalities. An acetyl group migration phenomenon was found during the synthesis of the O-acylated repeating unit of the P. aeruginosa ATCC 27577 antigen. All synthetic targets carried an amino functional group in the linker at the reducing end, thus facilitating further regioselective elaboration and biological studies. The synthetic strategy established here should be useful for the preparation of other similar oligosaccharides.