Date of Award

Winter 12-6-2022

Document Type

Thesis (Ph.D.)

Department or Program

Chemistry

First Advisor

Glenn C. Micalizio

Abstract

Tetracyclic triterpenoids are ubiquitous in nature and biology, with members displaying a wide range of medically relevant properties and occupying rather distinct regions of chemical space. Members of this large class include well-known steroid hormones and sterols as well as structurally interesting subclasses such as lanostanes and euphanes, among others. Comprised of the tetracyclic skeleton with three stereodefined quaternary centers at ring-junction positions, lanostanes and euphanes present synthetic challenges that are different from those encountered in efforts targeting the structurally less complex steroid hormones. Lanostanes, in particular, stand as a historically important class of compounds as significant attention has been directed at understanding the biosynthesis of lanosterol, the primary precursor to cholesterol, for the past 50 years. Though studies in this area have led to the development of new reaction methods and synthesis strategies, lanostanes and the structurally related euphanes continue to stand as challenges for asymmetric de novo synthesis. This thesis work describes progress towards the asymmetric total syntheses of lucidadone H, a hexanorlanostane natural product, and euphol, a euphane natural product. While the chemical technology that is central to both syntheses features metallacycle-mediated annulative cross-coupling, diastereoselective Friedel–Crafts cyclization and oxidative dearomatization/Wagner–Meerwein rearrangement to establish a functionalized tetracyclic intermediate, my efforts resulted in a concise synthesis of hexanorlanostanes, and an asymmetric approach to a C14-desmethyl euphane system, which was identified to be a novel modulator of the Liver X Receptor.

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