Synthesis of sesquiterpene-tropolones

A modular synthetic platform for the synthesis of the multi-bioactive sesquiterpene-tropolone natural products has been developed in an effort to provide general synthetic access to this class of compounds and related structures. In this work, the convergence of the sesquiterpene and tropolone fragments is enabled by a hetero-Diels–Alder reaction between a tropolone ortho-quinone methide and derivatives of α–humulene. Concise and scalable syntheses of both fragments are described, as well as alternative approaches to key intermediates. During the development of the tropolone synthesis, an unprecedented photochemical fragmentation was discovered. Two natural products, epolone B and deoxypycnidione have been synthesized employing this strategy, as well as two diastereomers of pycnidione. In these studies, a correction to the originally reported structure of epolone B is suggested based upon X-ray crystallographic data. The synthetic compounds were found to be cytotoxic to A459 and HCT116 cell lines. Current efforts are focused on synthesizing pycnidione in its correct relative stereochemical configuration. Future directions include application of these fragments in hetero-Diels–Alder reactions to synthesize related sesquiterpene-tropolones, other tropolone containing natural products, and bistropolone congeners for biological evaluation.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2019

Author dc:creator

• Bemis, Christopher Yngwie

Contributors dc:contributor

• Sarlah, David
• Denmark, Scott E.
• Hergenrother, Paul J.
• Silverman, Scott K.

• total synthesis
• organic synthesis
• sesquiterpene-tropolones
• meroterpenoids
• tropolone
• pycnidione
• epolone A
• epolone B
• eupenifeldin

Statement dc:rights

• Copyright 2019 Christopher Bemis

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/104826

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/104826