Studies Towards the Total Synthesis of Lancifodilactone G

Lancifodilactone G is a distinctive nortriterpenoid first isolated from the leaves of Schisandra lancifolia in 2005 by Sun and coworkers. Although it exhibits moderate anti-HIV activity and mild cytotoxicity, the presence of a rare aliphatic enol within this complex natural product presents a significant synthetic challenge. Given its limited availability from nature, we aimed to develop a scalable synthesis to support further biological evaluation and, more importantly, to investigate the origin and stability of the enol motif. This thesis describes the development of a convergent first-generation synthesis of the complete polyoxygenated carbon skeleton of lancifodilactone G, providing a foundation for further exploration of its structural complexity. Chapter 1 provides an account of lancifodilactone G, including its isolation, biosynthetic pathway, and biological activity, while also reviewing previous synthetic strategies toward this structurally complex natural product. Chapter 2 details the synthesis of the western fragment, which utilizes a chiral pool strategy to rapidly construct the tricyclic ABC ring system in 12 steps longest linear sequence and 3.2% overall yield. Chapter 3 describes the synthesis of the eastern fragment, featuring an asymmetric approach to furnish the densely functionalized F ring, including several contiguous stereocenters, achieved in 17 steps longest linear sequence in 2.5% overall yield. Chapter 4 describes the development of a highly convergent fragment coupling and a pinacol cyclization strategy to construct the eight-membered core, culminating in the synthesis of the complete polyoxygenated carbon skeleton of lancifodilactone G in 24 steps longest linear sequence in 0.3% overall yield. Chapter 5 outlines future directions for completing the first total synthesis of lancifodilactone G in as few as three remaining steps, including the development of a strategy to install the unprecedented enol motif. The insights gained from this work will provide critical insight into the origin and stability of the enol and potentially allow us to further probe its reactivity.

Department dc:contributor.department

Chemistry

Author dc:creator

• Conway, Alexander G.

Advisor dc:contributor.supervisor

• Evans, P. Andrew

• Total synthesis
• Lancifodilactone G

Statement dc:rights

• Attribution-NonCommercial-NoDerivatives 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1974/34445

OAI identifier oai:identifier

oai:queensu.scholaris.ca:1974/34445