Doctoral Dissertations

Date of Award


Degree Type


Degree Name

Doctor of Philosophy



Major Professor

David C. Baker


The research discussed in this dissertation focuses on the synthesis and biological evaluation of two families of therapeutic agents. In 1999 a group of scientists at the National Cancer Institute reported that during a screening of their database they had found an active non-nucleoside reverse transcriptase inhibitor. This compound (NSC-108406) was substantially more potent than the other inhibitors identified during their screening with an IC50 of 0.5 ± 0.3 μM. During a cell-based antiviral screen, it was found to provide an EC50 of 1.5 ± 1.0 μM. In an effort to increase the potency of the lead, a set of analogs of NSC-108406 was synthesized in our laboratories, providing a compound with an EC50 of 0.036 μM. Hydramycin is a naturally occurring pluramycinone that is a potent antimicrobial and antitumor agent and whose biological activity has created an interest in its synthesis. Our work began with a model study that established a strategy by which the pyranone system and associated functionality could be realized. The route makes use of a novel alkyne and a fluoride-induced ring closure that provided a molecule consisting of a chromenone with the essential moieties analogous to those of hydramycin. The protocol was applied to a compound containing the hydramycin anthraquinone system via a 2-formyl-1- hydroxy anthraquinone that was coupled with an alkyne.

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