Synthesis of a Pentasaccharide Fragment Related to the Inner Core Region of Rhizobial and Agrobacterial Lipopolysaccharides

Abstract

The pentasaccharide fragment α-d-Man-(1 → 5)-[α-d-Kdo-(2 → 4)-]α-d-Kdo-(2 → 6)-β-d-GlcNAc-(1 → 6)-α-d-GlcNAc equipped with a 3-aminopropyl spacer moiety was prepared by a sequential assembly of monosaccharide building blocks. The glucosamine disaccharide-as a backbone surrogate of the bacterial lipid A region-was synthesized using an 1,3-oxazoline donor, which was followed by coupling with an isopropylidene-protected Kdo-fluoride donor to afford a protected tetrasaccharide intermediate. Eventually, an orthogonally protected manno-configured trichloroacetimidate donor was used to achieve the sterically demanding glycosylation of the 5-OH group of Kdo in good yield. The resulting pentasaccharide is suitably protected for further chain elongation at positions 3, 4, and 6 of the terminal mannose. Global deprotection afforded the target pentasaccharide to be used for the conversion into neoglycoconjugates and "clickable" ligands.