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A catalytic asymmetric synthesis of palmerolide A

  • Author / Creator
    Penner, Marlin
  • In the Introduction of this thesis, consideration is given to historical and ongoing value of investing research efforts in the total synthesis of natural products. Following this discussion is an explanation of the factors that guided the selection of palmerolide A as a synthetic target. The current status of palmerolide A in the academic literature is overviewed in the remainder of the introductory chapter, followed by a summary of research objectives at the conclusion. Chapter Two begins with a consideration of overall synthetic strategy and then narrows the focus to synthetic investigations that were directed towards what is defined as the “Eastern Hemisphere” of palmerolide A. These investigations involved extension of an inverse electron demand hetero-Diels-Alder-cycloaddition/allylboration methodology catalyzed by Jacobsen’s chromium(III) catalyst that was developed in the research group of Professor Dennis Hall for application to this synthesis. This highly enantioselective methodology was employed to set the desired relative and absolute stereochemistry of the entire Eastern Hemisphere through the introduction of a borono-Ireland-Claisen rearrangement; a unique variation of the Ireland-Claisen rearrangement developed during the synthesis. Also detailed are challenges and strategies employed to overcome issues in selectivity, protecting groups, and purification culminating in an optimized synthetic route to the Eastern Hemisphere. This project was collaborative in nature and a portion of the unique contributions by collaborators Dr. Vivek Rauniyar and Dr. Ludwig Kaspar are briefly described in Chapter 3. Chapter 4 recounts the key synthetic steps employed to join the hemispheres (Suzuki-Miyaura coupling), close the ring (Yamaguchi macrolactonization), form the dienamide side arm (Curtius rearrangement) and complete the synthesis. Of note was the challenge of overcoming a problematic late stage deprotection of a p-methoxybenzyl group. Chapter 5 presents preliminary research directed towards the synthesis of palmerolide A analogues focussed on modification of the macrocyclic backbone with an aromatic ring and modifications in protecting group strategy to address the problem encountered in the total synthesis followed by a conclusion in Chapter 6.

  • Subjects / Keywords
  • Graduation date
    2011-11
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3VQ2SN33
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Department of Chemistry
  • Supervisor / co-supervisor and their department(s)
    • Hall, Dennis (Chemistry)
  • Examining committee members and their departments
    • Veinot, Jonathan (Chemistry)
    • Clive, Derrick (Chemistry)
    • Barriault, Louis (Chemistry)
    • West, Frederick (Chemistry)
    • Underhill, D. Alan (Oncology & Medical Genetics)