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    Phenanthropiperidine Alkaloids: Methodology Development, Synthesis and Biological Evaluation

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    Niphakis_ku_0099D_10757_DATA_1.pdf (9.527Mb)
    Issue Date
    2010-04-08
    Author
    Niphakis, Micah James
    Publisher
    University of Kansas
    Format
    376 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Medicinal Chemistry
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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    Abstract
    This work is directed towards the development of safe phenanthropiperidines for the treatment of cancer. It focuses on synthetic methodologies that facilitate their preparation and biological studies to better understand the neurological side-effects of the only alkaloid within this class to enter clinical trials: tylocrebrine. The preparation of cyclic enaminones in high enantiomeric purity is made possible through a one-flask, two-step protocol that uses mild Boc-deprotection conditions to suppress racemization. Elaboration of the enaminone scaffold was made possible with a direct palladium(II)-catalyzed arylation using aryltrifluoroborates as coupling partners. These methods give access to enantiomerically pure 3-arylpiperidines which were used as precursors of phenanthropiperidine alkaloids. A small phenanthropiperidine library was prepared and studied to elucidate the cause of tylocrebrine's neurological side-effects. Although the causes remain elusive, tylocrebrine and several of its analogs were found to bind to key biogenic amine receptors, disclosing another potential risk factor for their therapeutic use.
    URI
    http://hdl.handle.net/1808/6281
    Collections
    • Dissertations [4472]
    • Medicinal Chemistry Dissertations and Theses [81]

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    785-864-8983

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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