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

UoM administered thesis: Master of Philosophy

  • Authors:
  • Michael Hales

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.

Details

Original languageEnglish
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Award date1 Aug 2019