University of Illinois Urbana-Champaign

Synthesis of sesquiterpene-tropolones

Bemis, Christopher Yngwie

Content Files
BEMIS-DISSERTATION-2019.pdf

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

Description

Title
Synthesis of sesquiterpene-tropolones
Author(s)
Bemis, Christopher Yngwie
Issue Date
2019-04-15
Director of Research (if dissertation) or Advisor (if thesis)
Sarlah, David
Doctoral Committee Chair(s)
Sarlah, David
Committee Member(s)
  • Denmark, Scott E.
  • Hergenrother, Paul J.
  • Silverman, Scott K.
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2019-08-23T19:51:52Z
Keyword(s)
  • total synthesis
  • organic synthesis
  • sesquiterpene-tropolones
  • meroterpenoids
  • tropolone
  • pycnidione
  • epolone A
  • epolone B
  • eupenifeldin
Abstract
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.
Graduation Semester
2019-05
Type of Resource
text
Permalink
http://hdl.handle.net/2142/104826
Copyright and License Information
Copyright 2019 Christopher Bemis

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Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations and Theses - Chemistry