Date of Award:

5-2009

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Chemistry and Biochemistry

Committee Chair(s)

Bradley S. Davidson

Committee

Bradley S. Davidson

Committee

Alvan Hengge

Committee

Lisa Berreau

Committee

Roger Coulomb

Committee

Tom Chang

Abstract

Chapter 1 provides some background information on the disease area of cancer and current modes of treatment. Chemotherapy treatment is discussed with a focus on the major cellular targets for these drugs: DNA and microtubules. For each target, classes of active compounds are described along with their mode of action. The microtubule stabilizing agent laulimalide is introduced and a case is made for analogue synthesis.

Chapter 2 describes our first generation efforts toward synthesis of des-methyl laulimalide. The target compound is divided into a northern and southern fragment with the synthesis of each fragment described. The preparation of landmark intermediates along the synthetic route is also described.

Chapter 3 presents our ongoing efforts toward a second generation synthesis of des-methyl laulimalide. Our progress toward a des-methyl,des-pyran analogue is covered as well.

Chapter 4 reviews progress in the area of laulimalide analogue development. Biological assay results and the first insights into structure-activity-relationships are described.

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9cdd68107878b30b83591aeb39f43472

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