Towards chemical synthesis of the Pseudomonas aeruginosa 1244 pilin glycan

Abstract

Pseudomonic acid (Pse) and its derivatives broadly exist in nature. Their chemical and biological properties are less investigated, because of the low efficiency of chemical synthesis. Comparatively, as a diamino sugar, Pse is much complicated than other ulosonic acid, including sialic acid, KDN and KDO. The naturally occurring substitutions on nitrogen of C-5 and C-7 are usually different. This difference increases the difficulty of its synthesis. Till now, the synthesis of Pse derivative with orthogonal protections on C-5 and C-7 has not been reported.

The thesis developed a concise route to synthesize Pse derivatives with orthogonally protected diamine groups. This work laid the foundation for the preparation for the investigation of Pse glycosylation.

The pilin glycan of Pseudomonas aeruginosa 1244 is a trisaccharide containing Pse, D-xylose and D-fucosamine. It has been identified and demonstrated with immunological properties. The thesis aims to develop the chemical synthesis of this trisaccharide. Both glycosylation between three monosaccharides are unknown.

The chemical syntheses of D-xylose building blocks and D-fucosamine building blocks are also achieved in this thesis. And the glycosylation between D-xylose and D-fucosamine is realized.

With the building blocks in hand, the glycosylation of Pse is studied towards the total synthesis of Pseudomonas aeruginosa 1244 pilin glycan.