Date of Award
1-1-2021
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
Dr. Sudeshna Roy
Second Advisor
Dr. David Colby
Third Advisor
Dr. Hoang Le
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Fluorinated compounds have been routinely synthesized in the pharmaceutical and agricultural industries. Approximately, 45% of drugs approved by the U.S. Food and Drug Administration in 2018−2019, and 52% of agricultural products between 2010 and 2017 were fluorinated compounds. In comparison to their non-fluorinated counterparts, fluorinated drugs have different pharmacokinetics and pharmacodynamics profiles. Bond strength and electronegativity of the fluorine atom can affect the compound's pKa, dipole moment, and metabolic stability. Therefore, methods to access fluorinated compounds are highly pursued in organic synthesis. Various fluorinating agents (nucleophilic and electrophilic) have been developed over the last few decades and are widely employed in organic synthesis. Fluorinecontaining building blocks are a practical method to synthesize fluorinated targets.
This thesis aims to extend the applications of fluoronitroalkenes as a fluorinated building block in 1,3-dipolar cycloaddition and 1,4-conjugate addition reactions to construct a variety of mono-fluorinated molecules. It is well established that fluoronitroalkenes undergo 1,3-dipolar cycloaddition. This process has been successfully used to access 4-fluoropyrazoles in the presence of in-situ prepared hydrazones and acetic acid. Furthermore, fluoronitroalkenes also used to synthesize 4-fluoro-triazole analog of fentanyl, which are under biological valuation. Radioligand binding assay was conducted and showed a drop in the binding affinity for μ-opioid receptors.
The applications of fluoronitroalkenes have been extended to 1,4-conjugate addition reactions using organocatalysis. A conjugate addition is a method for forming carbon-carbon or carbon–heteroatom bonds. Using organocatalysis, trimethylsilyl azide served as a nitrogen-based nucleophile to create a carbon–nitrogen bond asymmetrically. At the present, our laboratory is optimizing this reaction under various conditions and catalysts.
Recommended Citation
Alrefaei, Hamdan Eid, "Applications of Fluoronitroalkenes in 1,3-Dipolar Cycloaddition and 1,4-Conjugate Addition" (2021). Electronic Theses and Dissertations. 2658.
https://egrove.olemiss.edu/etd/2658