Author ORCID Identifier

https://orcid.org/0009-0007-6160-0201

Date of Award

Summer 8-7-2024

Document Type

Thesis (Ph.D.)

Department or Program

Chemistry

First Advisor

Glenn C. Micalizio

Abstract

Tetracyclic triterpenoids have a rich history in biology, medicine, and chemistry. In terms of pharmaceutical relevance, compounds with this scaffold are one of the most successful classes with over 100 FDA approved examples. Despite this success, the vast majority of compounds within this class are prepared through semisynthesis. While this approach is undeniably successful, judged by the sheer number of medications generated, it also has limitations. Namely, semisynthesis requires the use of complex starting materials that have fixed absolute stereochemistry and often sparse functionality. One approach to address the inherent limitations with semisynthesis is through de novo synthesis. Recently, our group has put significant effort into establishing novel de novo synthetic organic chemistry to access unique tetracyclic triterpenoid systems. This thesis outlines my contributions to this body of work, including: (1) the development of a stereoselective Friedel–Crafts cyclization that allows access to C9-C13 anti-substituted tetracyclic triterpenoid systems (2) the design and synthesis of the enantiomeric estranes for glucocorticoid receptor modulation and (3) the first asymmetric total syntheses of (+)-euphol and (+)-tirucallol. It is our belief that the chemistry developed through these studies have the potential to be useful for the preparation of biologically relevant systems that would be difficult to access through any other means. Additionally, it is our hope that the work done in this thesis will be helpful to inspire new research to be done on these fascinating and complex systems.

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