Synthesis Towards a Constrained Paclitaxel Analog 公开

Kimzey, Clinton James (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/mg74qn037?locale=zh
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Abstract

Since its discovery in the 1960s, pacilitaxel (PTX) has been one of the most important discoveries in the field of cancer therapeutics, and is currently used in the treatment of metastatic breast cancer, ovarian carcinoma, and AIDS-related Kaposi-Sarcoma. PTX works by binding to the β-tubulin subunit of cellular microtubules, and this PTX-tubulin complex stabilizes the microtubule structure preventing cells from completing mitotic division. In an effort to synthesize more targeted analogs of PTX, researchers have been trying to determine the conformation PTX assumes upon binding the β-tubulin subunit. In recent years, there have been two major conformations suggested. The first is the T-Taxol conformation suggested by James P. Snyder of Emory University and the second is the REDOR-Taxol conformation suggested by Iwao Ojima of Stony Brook University. Because these two conformations contain many similarities, it is difficult to determine which is the correct conformation. It is therefore the purpose of this research to synthesize a constrained PTX analog that has the potential to shed light on this topic.

Table of Contents

List of Figures
List of Schemes
List of Abbreviations
I. Introduction
Taxol: A History and Introduction...1
Microtubules: Background and Interactions with Taxol...4
Conformationally Constrained Taxol...6
II. Results and Discussion
Results and Discussion...8
Conclusion...11
Future Plans...12
III. Experimental
Experimental Methods...12
Experimental...13
References...20





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