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dc.contributor.advisorGeorg, Gunda I.
dc.contributor.authorNiphakis, Micah James
dc.date.accessioned2010-06-09T03:01:12Z
dc.date.available2010-06-09T03:01:12Z
dc.date.issued2010-04-08
dc.date.submitted2010
dc.identifier.otherhttp://dissertations.umi.com/ku:10757
dc.identifier.urihttp://hdl.handle.net/1808/6281
dc.description.abstractThis 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.
dc.format.extent376 pages
dc.language.isoEN
dc.publisherUniversity of Kansas
dc.rightsThis item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
dc.subjectOrganic chemistry
dc.subjectPharmaceutical chemistry
dc.subjectEnaminone
dc.subjectPalladium
dc.subjectPhenanthropiperidine
dc.subjectTylocrebrine
dc.subjectTylophora indica
dc.subjectTylophorine
dc.titlePhenanthropiperidine Alkaloids: Methodology Development, Synthesis and Biological Evaluation
dc.typeDissertation
dc.contributor.cmtememberAubé, Jeff
dc.contributor.cmtememberHanson, Paul R.
dc.contributor.cmtememberGrunewald, Gary L.
dc.contributor.cmtememberDutta, Apurba
dc.thesis.degreeDisciplineMedicinal Chemistry
dc.thesis.degreeLevelPh.D.
kusw.oastatusna
kusw.oapolicyThis item does not meet KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


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