Date of Award

Summer 6-10-2024

Document Type

Thesis (Ph.D.)

Department or Program

Chemistry

First Advisor

Glenn C. Micalizio

Abstract

Natural products have long served as a stimulus for growth and innovation to advance the field of organic chemistry. This thesis describes efforts in complex molecule synthesis that demonstrate the broad value of programs in natural product total synthesis and natural product-inspired function-oriented synthesis. The first part of this thesis describes a function-oriented synthesis approach to pentacyclic triterpenoids through design of a simplified 26-norpentacyclic triterpenoid platform to promote future medicinal exploration in this area. These studies yielded a divergent asymmetric synthesis of 26-norgermanicol and 26-norlupeol as well as the discovery of a new class of androgen receptor antagonist that is ~6x more potent than the natural product lupeol. The second part of this thesis describes studies aimed at developing a new strategy for the synthesis of oxygenated carbocycles to address challenges associated with the synthesis of highly oxygenated terpenoid natural products. These efforts resulted in the invention of a suite of novel annulation processes for the union of alkynes with dicarbonyl systems. Application of this designed annulation is highlighted by use in a total synthesis of anhydroryanodol that constitutes a formal total synthesis of ryanodol.

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