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Exploring the chemical space around austdiol by semi-synthesis

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thesis
posted on 2023-01-24, 23:15 authored by Stefan Valter

Natural products provide structurally diverse chemical scaffolds with applications in pharmaceuticals and agrichemicals. However, many natural products do not possess PK/PD properties suitable for direct application as chemotherapeutic agent. When isolated material is sufficient, semi-synthetic modification of a natural product scaffolds is a useful technique for exploring chemical space around a pharmacophore to improve bioactivity and druggability. In this thesis, chemical derivatisation was used to expand the chemical space around austdiol, a toxic azaphilone first isolated in 1973 from the fungus Aspergillus ustus. A small semi-synthetic library of fourteen austdiol analogues was synthesised, focusing primarily on degradation, reduction, oxidation and amination reactions. Their structures were determined by HRESIMS and spectroscopic methods, including NMR and UV-vis. These derivatives were screened for antibacterial, antifungal, and cell cytotoxic activities. Finally, a 2,4-dinitrophenylhydrazone derivative of austdiol was explored as a chiral derivatisation agent to assist in the resolution of L and D enantiomers of amino acids commonly found in natural products, by UV-vis detection in reversed-phase liquid chromatography.

History

Table of Contents

1. Introduction -- 2. Stability of Austdiol -- 3. Semi-synthetic Derivatives of Austdiol -- 4. The Biological Activity of Austdiol and Related Analogues -- 5. Austdiol-DNP as an Amine Derivatising Agent -- 6. Austdiol-DNP as a Chiral Derivatising Agent -- 7. Concluding Remarks -- 8. Experimental -- 9. References -- 10. Supplementary Data

Awarding Institution

Macquarie University

Degree Type

Thesis MRes

Department, Centre or School

School of Natural Sciences

Year of Award

2022

Principal Supervisor

Andrew Piggott

Additional Supervisor 1

Joanne Jamie

Rights

Copyright: The Author Copyright disclaimer: https://www.mq.edu.au/copyright-disclaimer

Language

English

Extent

74 pages