Synthesis of Sulfamide Analogues of DPA in Anti-TB Drug Development
Degree GrantorUniversity of Canterbury
Degree NameMaster of Science
In 2009, approximately 1.7 million people died of tuberculosis. The emergence of drug-resistant strains of Mycobacterium tuberculosis (M. tuberculosis) has created an urgent demand for the development of new anti-tuberculosis (anti-TB) drugs and treatments. M. tuberculosis, the causative agent, has a protective complex cell wall structure that is essential for its survival. One of the major building blocks of the cell wall structure is an arabinofuranosyl polysaccharide called arabinan. Since arabinan is not present in mammals, it has become a promising target for anti-TB drug development. The arabinan component is biosynthesized by a family of arabinofuranosyltransferases (araTs) using the substrate decaprenolphosphoarabinose (DPA) as the donor of arabinose. This project targets the biosynthesis of arabinan by synthesizing analogues of DPA as potential inhibitors of araTs. A sulfamide moiety was chosen as an isosteric replacement of the phosphate group of DPA. To mimic the polyprenyl chain of DPA, a series of alkyl chains of varying length and a triethylene glycol (TEG) derived chain were used.