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Intramolecular conjugate displacement for making carbocycles and studies on the total synthesis of MPC1001

  • Author / Creator
    Wang, Lihong
  • The first chapter of this thesis describes methodology on an all-carbon intramolecular conjugate displacement between a carbon nucleophile and a Morita-Baylis-Hillman adduct for making carbocyclic skeletons. The reaction scope was examined with different electron-withdrawing groups, types of carbon nucleophile and leaving groups. The study demonstrated that this transformation is a convenient and effective way of constructing carbocycles, including some synthetically challenging structures. The mechanism of this transformation was probed by experiments designed to trap a possible anionic species of a non-concerted pathway. The second part of my thesis describes studies towards the total synthesis of the natural product MPC1001, which is a potential anti-tumor agent. Effort was focused on inventing a way of installing a disulfur bridge in a stereo-controlled manner. Difficulties were encountered for thiol deprotection, as attempted removal of many known thiol-protecting groups gave either no reaction or loss of the sulfur, possibly expelled by the nitrogen on the same carbon. Therefore, a new protecting group for thiols was designed, which could be deprotected under mild conditions. Although this protecting group allowed smooth deprotection with one specific reagent, additional problems prohibited carrying the research further using this group. A new route for installing the disulfide bridge was conceived and is still under examination.

  • Subjects / Keywords
  • Graduation date
    2011-11
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3M39W
  • 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)
    • Clive, Derrick L.J. (Chemistry)
  • Examining committee members and their departments
    • Weinfeld, Michael (Oncology)
    • Li, Liang (Chemistry)
    • Clive, Derrick L.J. (Chemistry)
    • Back, Thomas G. (Chemistry, University of Calgary)
    • Lowary, Todd L. (Chemistry)
    • Vederas, John C. (Chemistry)