A simple iterative method for the synthesis of β-(1→6)-glucosamine oligosaccharides

Poly-N-acetylglucosamine (PNAG) saccharides are an important constituent of bacterial biofilms, such as those produced by Staphylococcus aureus. We have developed a simple two-step iterative method for the synthesis of β-(1→6)-glucosamine oligosaccharides that are structurally similar to PNAG. We illustrate the method with the formation of a pentasaccharide. The key building block is an orthogonally protected N-trifluoroacetamido thioglycoside donor that was added in succession to a glycosyl acceptor, enabling efficient glycosylation of the growing chain. In the second step of the iterative cycle, this building block is quantitatively deprotected at the C-6-hydroxyl position, ready for the next saccharide addition. Building from an azido-functionalised GlcNAc monosaccharide acceptor, the pentasaccharide was synthesised in seven steps in an overall yield of 25%.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Efficient, scalable and high yielding syntheses of β-(1→6)-glucosamine oligosaccharides. ► Use of N-trifluoroacetyl substituted donors provides a simple and much-needed alternative to the N-phthalimido-protected donors utilised in many methodologies to date. ► A two-step, iterative process applied to generate the protected pentasaccharide in an overall yield of 25%. ►Saccharide oligomers may be useful in the preparation of vaccines targeting bacterial biofilms.