Synthesis of sesquiterpene-tropolones

Bemis, Christopher Yngwie

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

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

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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