Application of the Diels-Alder reaction towards the total synthesis of embellistatin and natural product Inspired libraries

Download files
Access & Terms of Use
open access
Embargoed until 2016-01-31
Copyright: Nash, Justin
Altmetric
Abstract
Natural products are useful in the drug discovery paradigm, both as drugs and as inspiration for new scaffolds. This thesis is concerned with the synthetic work towards the asymmetric total synthesis of embellistatin, a novel anti-mitotic and anti- angiogenesis natural product. It is also concerned with the synthesis of a natural product-inspired library. Chapter 1 provides an introduction to natural products, small-molecule libraries and the Diels-Alder reaction as a method to construct such complex systems. Chapter 2 discusses the asymmetric synthesis towards the natural product embellistatin. Initially this involved the diastereoselective synthesis of a stereotriad containing the stereochemical information of the natural product. Subsequently, a diene- regenerative Diels-Alder approach was used to prepare the core of the natural product. In addition, methods for the construction and introduction of the two sidechains required to complete the natural product were examined. Chapter 3 describes the synthesis of a natural product-inspired library. Inspired by natural products like that of embellistatin, a natural product-inspired library based on fused heterobicyclic scaffolds was examined. A number of fused scaffolds were prepared using a Diels-Alder strategy. The scaffolds prepared were also subjected to an additional diversification step. In total, 73 compounds were synthesised during this project and have been submitted to the National Institutes of Health (NIH) Molecular Libraries Small Molecule Repository (MLSMR). A summary of the work and future directions for each project is given at the end of the respective chapter.
Persistent link to this record
Link to Publisher Version
Link to Open Access Version
Additional Link
Author(s)
Nash, Justin
Supervisor(s)
Morris, Jonathan
Creator(s)
Editor(s)
Translator(s)
Curator(s)
Designer(s)
Arranger(s)
Composer(s)
Recordist(s)
Conference Proceedings Editor(s)
Other Contributor(s)
Corporate/Industry Contributor(s)
Publication Year
2013
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
Files
download public version.pdf 9.65 MB Adobe Portable Document Format
Related dataset(s)