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

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.

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

2016

Author dc:creator

• Hicklin, Robert W

Contributors dc:contributor

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

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

Statement dc:rights

• Copyright 2015 Robert Hicklin

Language dc:language

en

Handle dc:identifier

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

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/89201