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).

在本篇论文中，我展示了我在两个主要项目上的研究成果；即 Cruentaren A 及其类似物的天然产物合成，以及 Hsp90ß 选择性抑制剂的合成。论文首先对 F1FO ATP 合成酶和 Hsp90ß 进行了详尽的介绍，随后阐述了评估多个手性中心构型异构化以及 Cruentaren A 后期修饰的 Cruentaren A 类似物的开发。研究随后转向一系列 Hsp90ß 选择性抑制剂的开发，以评估结合口袋中的溶剂暴露区域，最终，设计了 Hsp90ß 选择性赖氨酸靶向的共价抑制剂（TCIs）。