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Synthetic Studies of Laulimalide Analogues

by McAlexander, Ian Addison

Abstract (Summary)
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.
Bibliographical Information:

Advisor:

School:Utah State University

School Location:USA - Utah

Source Type:Master's Thesis

Keywords:des methyl laulimalide microtubule stabilizer synthesis

ISBN:

Date of Publication:05/01/2009

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