Electronic Theses and Dissertations

Date of Award


Document Type


Degree Name

Ph.D. in Pharmaceutical Sciences


Pharmaceutics and Drug Delivery

First Advisor

David A. Colby

Second Advisor

Joshua Sharp

Third Advisor

Hoang V. Le

Relational Format



Fluorine chemistry plays a diverse role in the pharmaceutical, agricultural, and material industries. In fact, around 25% of pharmaceuticals and 40% of agrochemicals contain at least one fluorine atom. The incorporation of fluorine into pharmaceuticals or natural products can increase bioavailability by enhancing lipophilicity, metabolic stability, and overall pharmacokinetics properties. Our laboratory has designed a method to generate difluoroenolates from pentafluoro-gem-diols. This reactivity can be used to produce molecules displaying a difluoromethyl group. The reaction occurs through the release of trifluoroacetate. We improved the design and synthesis of fluorinated derivatives of flavones and measured their antioxidants activities. This work expanded the understanding of structure-activity relationships of the flavone class of natural products for use in neurodegenerative disorders. The search for selective and more efficient fluorination methods is of interest to academia and industry as the demand for fluorinated building blocks increases. We utilized the difluoroenolates from the trifluoroacetate releases in synthesizing difluorinated α-haloketones and alcohols. This work enables the preparation of valuable difluorinated molecules, which can serve as building blocks in drug discovery. We also investigated the reactivity of under-explored fluorinated functional groups, like the pentafluorosulfanyl group. The pentafluorosulfanyl (SF5) group is one of the most recent additions to the fluorinated functional groups. We characterized the stability of the pentafluorosulfanyl group by examining different aromatic pentafluorosulfanyl compounds. We believe these studies will introduce novel reactivity that can be utilized to develop fluorinated molecules.

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