Synthetic studies directed towards hunanamycin, teixobactin and telomycin antibiotic natural products and their analogues

Thomas, Carys (2018) Synthetic studies directed towards hunanamycin, teixobactin and telomycin antibiotic natural products and their analogues. Doctoral thesis, University of East Anglia.

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The emergence of bacteria resistant to all clinically approved antibiotics has led to a worldwide search for new drugs. Without new antibiotics many aspects of modern medicine would become nearly impossible.
One possible solution is to use natural products which show antibacterial activity as the starting point for new antibiotics. Sometimes new natural products act upon well-known targets. However, sometimes they will show previously unknown modes of action. One natural product which acts upon a new target is hunanamycin A, a small molecule inhibitor of the riboflavin synthase enzyme, an enzyme not found in mammalian cells. A new synthesis of hunanamycin A has been achieved, using ribose as a starting material. The synthesis can easily be adapted to make new analogues to improve the activity of hunanamycin A.
Teixobactin is a macrocyclic lariat depsipeptide showing excellent activity against Gram-positive bacteria, by targeting lipid II and III to prevent cell wall biosynthesis. Teixobactin is made up from a 13 membered depsipeptide macrocycle containing the non-proteinogenic amino acid enduracididine and a seven amino acid linear tail. Arginine was substituted for enduracididine in this research. A combination of solid phase and solution phase synthesis were then used in research towards teixobactin analogues for testing in order to improve the pharmacological properties and understand the structure-activity relationship.
Another macrocyclic depsipeptide showing antibacterial activity is telomycin. A combination of solid and solution phase synthesis may also be used to make analogues of telomycin for structure-activity relationship.
In summary, synthetic studies based on natural products showing antibacterial activity has been carried out in order to work towards the development of new antibiotics.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Stacey Armes
Date Deposited: 12 Apr 2019 11:36
Last Modified: 12 Apr 2019 11:36


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