The Synthesis of Analogs of Cruentaren A and Hsp90B-Selective Inhibitors

In this dissertation, I present my work performed on two main projects; the natural product synthesis of Cruentaren A and analogs thereof, and the synthesis of Hsp90ß-selective inhibitors. A thorough introduction to F1FO ATP synthase and Hsp90ß is provided, followed by the development of Cruentaren A analogs that evaluate the epimerization of several chiral centers as well as late-stage modifications of Cruentaren A. The work then shifts to the development of a series of Hsp90ß-selective inhibitors to evaluate the solvent-exposed region of the binding pocket, and finally, the design and development of Hsp90ß-selective lysine targeted covalent inhibitors (TCIs).