Author ORCID Identifier
https://orcid.org/0009-0000-5150-7125?lang=en
Date of Award
Spring 5-27-2025
Document Type
Thesis (Ph.D.)
Department or Program
Chemistry
First Advisor
Glenn Micalizio
Abstract
The complex molecular scaffolds of tetracyclic triterpenoid natural products continue to inspire novel chemical reactions. Steroid-based drugs have contributed significantly to human health in the past century, demonstrating a broad range of therapeutic applications including anti-viral, anti-inflammatory, and anti-cancer activities. However, the efficient and flexible synthesis of tetracyclic triterpenoids remains an unsolved problem. Despite numerous reports of medically relevant bioactivity associated with cucurbitanes, lanostanes, and cardenolides, exploration of their pharmaceutical promise has been limited by a lack of access to molecules bearing their requisite carbon frameworks. Prior to the initiation of my doctoral research, there were no reported syntheses of any cucurbitane natural product and only three reported syntheses of lanostanes. Our efforts to establish robust chemical methods to populate this pharmaceutically privileged chemical space has culminated in the following progress: (1) the first total synthesis of a cucurbitane natural product, octanorcucurbitacin B; (2) a novel cucurbitane-to-lanostane rearrangement affording an enantiomeric lanostane system; and (3) efforts towards the first asymmetric total synthesis of sarmentogenin, a cardenolide.
Recommended Citation
Bucknam, Andrea Rachel, "Progress towards the asymmetric de novo synthesis of tetracyclic triterpenoids: cucurbitanes, lanostanes, and cardiotonic steroids" (2025). Dartmouth College Ph.D Dissertations. 372.
https://digitalcommons.dartmouth.edu/dissertations/372
