Title

Part I. A 2-nitroimidazole indocyanine green dye derivative tumor imaging agent. Part II. A dichlorination-reductive-dechlorination route to N-acetyl-2-oxazolone. Part III. Intramolecular Diels-Alder approach to the synthesis of pancratistatin

Date of Completion

January 2007

Keywords

Chemistry, Organic|Health Sciences, Oncology

Degree

Ph.D.

Abstract

Over half a million Americans are expected to die from cancer this year alone. Early detection of cancerous tumors and effective treatments are vital to improve these numbers. Chapter 1 focuses on the synthesis of a 2-nitroimidazole containing indocyanine green dye derivative that has the potential to be a successful cancer imaging agent. The 2-nitroimidazole portion of the molecule is designed to aid in the accumulation of the entire molecule in cancerous tumors. The indocyanine green dye derivative portion of the molecule uses NIR light to image the tumors. This combination would enable doctors to image tumors that are currently too small to be seen by MRI and PET. Chapter 2 reports a new synthesis of 2-oxazolone, a heterocycle necessary for the proposed synthesis of the natural product pancratistatin in Chapter 3. The synthesis utilizes the dichlorination of the starting material, N-acetyl-2-oxazolidinone, as a route to the product. Pancratistatin is a phenanthridone alkaloid that possesses phenomenal anti-cancer properties; yet its natural abundance is too low for adequate amounts to be isolated and tested as a possible cancer treatment. Although there have been previous syntheses of the natural product, none have been high yielding enough to facilitate complete biological testing of the molecule. The proposed synthesis focuses on an intramolecular Diels-Alder reaction to overcome several of the synthetic challenges in the molecule. The intramolecular Diels-Alder reaction successfully creates the skeleton of pancratistatin, however, the stereochemistry around the B/C ring juncture is incorrect. Epimerization of one of the stereocenters is being investigated. ^