Chemical diversification of the natural products quinine, abietic acid and pleuromutilin by ring distortion

Hicklin, Robert W

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https://hdl.handle.net/2142/89201 Copy

Description

Title

Chemical diversification of the natural products quinine, abietic acid and pleuromutilin by ring distortion

Author(s)

Hicklin, Robert W

Issue Date

2015-11-18

Director of Research (if dissertation) or Advisor (if thesis)

Hergenrother, Paul J

Doctoral Committee Chair(s)

Hergenrother, Paul J

Committee Member(s)

• Moore, Jeffrey S
• White, M. Christina
• Bailey, Ryan C

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Ring Distortion
• Natural Products
• Organic Synthesis
• Quinine
• Abietic Acid
• Pleuromutlin
• Fenestrane

Abstract

Ring distortion reactions directly alter the core ring systems of small molecules and can lead to striking changes in molecular structure. Strategic application of ring distortion reactions to complex molecules, such as natural products, is an effective method for the generation of compounds that exhibit significant molecular complexity, but possess vastly different molecular structures. The compounds produced by this complexity to diversity approach are advantageous starting points for the discovery of new biologically active compounds, as they possess a level of molecular complexity found in approved drugs but lacking in other screening collections used in drug discovery. The chapters herein emphasize the utility of ring distortion reactions for modifying complex molecules and assert the potential of ring distortion as strategy for the synthesis of complex and diverse small molecules. Chapter 1 defines the different methods of ring distortion and demonstrates how these reactions can be employed for the selective modification of complex molecules. Chapter 2 focuses on the application of ring distortion reactions to the cinchona alkaloid natural product quinine towards the creation of a collection of complex and diverse small molecules. Chapter 3 details the ring distortion of the terpene natural product abietic acid and details strategies for the synthesis of derivative libraries from the products of ring distortion. Chapter 4 describes on the ring distortion of the terpene natural product pleuromutilin and the discovery of a pleuromutilin-derived compound with anticancer activity.

Graduation Semester

2015-12

Type of Resource

text

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http://hdl.handle.net/2142/89201

Copyright and License Information

Copyright 2015 Robert Hicklin

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