<p>This dissertation focuses on three main projects that include aspects of natural product synthesis, synthetic methodology, as well as the development of a small molecular probe for the study of protein palmitoylation. This first project introduces studies towards the synthesis of manassantins A and B which are potent inhibitors of hypoxia-inducible factor 1 (HIF-1). In addition, the preparation of manassantin A analogues is described along with preliminary structure-activity relationship (SAR) studies providing further insight into the structural requirements for HIF-1 inhibitory activity. The second project describes efforts towards the development of a fluorescence resonance energy transfer (FRET)-based assay system to characterize the palmitoylation of oncogenic Src family kinases. The initial work on this project involves the synthesis of a modified lipopeptide mimicking the critical N-terminus sequence of Src signaling proteins required for activation. Lastly, the third project focuses on the development of an asymmetric organocatalytic method to synthesize 2,7-cis- and 2,7-trans oxepanes as well as its application to the preparation of a simple cyclic ether. Ultimately, the goal of this work would be to extend this methodology to the preparation of complex, biologically active cyclic ethers.</p> / Dissertation
| Identifer | oai:union.ndltd.org:DUKE/oai:dukespace.lib.duke.edu:10161/3069 |
| Date | January 2010 |
| Creators | Kasper, Amanda Clare |
| Contributors | Hong, Jiyong |
| Source Sets | Duke University |
| Detected Language | English |
| Type | Dissertation |
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