| Chapter 1: This chapter gives a brief history of alpha-hydroxytropolones, how they were discovered and unique properties of these substrates. Included is a background on the bioactivity of these substrates in cellular targets such as bacteria, fungi, parasites, tumors and toxicity, as well as their ability to inhibit various metallo-based enzymes. Structure activity relationships studies are reviewed on important metalloenzymes HIV-Reverse Transcriptase (RT) and Inositol monophosphatase (IMPase). Finally the chapter finishes with a synthetic overview of alpha-hydroxytropolones including natural product targets such as puberulic acid, puberulonic acid, beta-thujaplicinol, and alpha-hydroxytropolone.;Chapter 2: A brief review on beta-hydroxy-gamma-pyrone based oxidopyrylium cycloadditions will be presented as well as important oxidopyrylium cycloaddition/ring opening procedures to yield natural tropolone products. Research from the Murelli laboratory will be highlighted. This chapter will discuss a new synthetic route toward functionalized alpha-hydroxytropolones. A beta-hydroxy-gamma-pyrone intermolecular oxidopyrylium cycloaddition with a range of alkynes that was optimized to an efficient and high yielding process will be discussed. Next two ring catalyzed ring openings will be discussed; one that utilizes boron trichloride that attains alpha-hydroxytropolones and 7-methoxytropolones, and a triflic acid mediated sequence that yields exclusive 7-methoyxtropolones and furans. Finally, a new reaction with the oxidopyrylium species will be highlighted that shows the exchange of alcohols in these reactive species.;Chapter 3: Chapter three describes the background on three specific medicinal targets: ANT (2")-Ia, HIV RT RNase H, and HBV RT RNaseH and preliminary structure activity relationship studies with alpha-hydroxytropolones synthesized in this research are outlined. |
