Off-campus UNL users: To download campus access dissertations, please use the following link to log into our proxy server with your NU ID and password. When you are done browsing please remember to return to this page and log out.
Non-UNL users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
18F-Labeling of Aromatic Amines for Molecular Imaging
By developing protection schemes for drug-like amines, I have expanded the scope of diaryliodonium salt labeling chemistry. Diaryliodonium salts are well-known intermediates for the preparation of labeled compounds, particularly 18F-fluorinated arene imaging agents for positron emission tomography (PET). PET imaging is an established non-invasive imaging technique used for the diagnosis and staging of diseases such as cancer and Alzheimer's. Despite the utility of PET and the importance of 18F-fluoride in the preparation of PET radiotracers, chemists still struggle to incorporate fluorine-18 into electron-rich arenes efficiently. There are several challenges to the introduction of [18F]fluorine for the preparation of PET tracers: time (< 2 h), scale (~1 ng fluorine-18), and high isotopic purity requirements. In practice, these considerations require that the source of fluorine-18 is 18F-fluoride, and that only nucleophilic reactions can be considered. In the DiMagno laboratories, we have developed an efficient, nucleophilic method to incorporate 18F-fluoride into a wide array of aromatic compounds. The scope of substrates that can be radiolabeled using diaryliodonium salts is broad, but has several limitations. Reducing functional groups such as free N-H groups and tertiary sp3-hybridized amines are incompatible with the strongly oxidizing iodine(III) center. Additionally, diaryliodonium salt stability and regiochemical control suffer when particularly electron-rich aryl groups, such as anilines, are substituents on iodine(III). These synthetic hurdles can be overcome by use of a protecting group strategy. Installing electron-withdrawing protective groups on the aniline nitrogen opens a straightforward route to functionalizing and radiolabeling aminoaryl substituents in relatively complex molecules. I have also developed a novel protecting group using tetra-alkyl quaternary ammonium salts that allows functionalization of arenes containing sp3-hybridized amines via diaryliodonium salts. Using these protection schemes, I have successfully radiofluorinated several compounds of interest that were previously inaccessible using diaryliodonium salts.
Linstad, Ethan J, "18F-Labeling of Aromatic Amines for Molecular Imaging" (2018). ETD collection for University of Nebraska - Lincoln. AAI10790690.