The Synthesis of Constituents of Wall Teichoic Acids, Integral Components of Gram Positive Bacterial Cell Walls

Abstract

The synthesis of wall teichoic acids, complex proteoglycans found on the surface of gram positive bacteria, has become a major area of interest in recent years because it has been established that they form a major role in the bacterium’s immunological defence against number of antibiotics. In this study two components of a wall teichoic acid found in the methicillin resistant Staphylococcus aureus bacteria were attempted to be synthesised: D-mannosamine, the less common isomer of D-glucosamine, which is part of a disaccharide linkage unit found in all wall teichoic acids. This was synthesised with limited success as an expected alcohol to azide reaction via a triflate intermediate, proved to remove neighbouring protecting groups, and other routes will have to be attempted to reach D-mannosamine. D-ribitol protected on the 1-OH with DMTr and the middle OH groups protected by benzylation, with a free 5-OH ready to be attached to a solid support and used in automated DNA synthesis to make the oligosaccharide found in Staphylococcus aureus. This route was more successful, although benzylation and removal of the 5-OH protecting group is still required to reach the desired monomer which could be taken forward to solid state synthesis via the phosphoramidite approach to produce WTA oligomers.

Date of Award	1 Aug 2019
Original language	English
Awarding Institution	The University of Manchester
Supervisor	John Gardiner (Supervisor) & Gordon Jayson (Supervisor)