Copper-mediated nucleophilic 18F-radiolabelling of (hetero)arenes for applications in positron emission tomography

Thesis

This thesis focuses on the development of a novel nucleophilic ¹⁸F-fluorination of (hetero)arenes and of a rapid screening experiment to facilitate the application of this reaction to complex heterocyclic targets of medicinal importance.

Chapter 1 introduces the use of molecules labelled with fluorine-18 as tracers in positron emission tomography and reviews methods for the preparation of [¹⁸F]fluoroarenes published prior to the start of the work in this thesis.

Chapter 2 describes the development of a novel method for the preparation of electronically-diverse [¹⁸F]fluoroarenes from aryl boronic esters and [¹⁸F]fluoride, mediated by a copper complex. Application of this ¹⁸F-fluorodeboronation to electron-rich radiotracers is demonstrated. Methods for the preparation of [¹⁸F]fluoroarenes published after the start of the work in this thesis are reviewed.

Chapter 3 outlines a rapid screening experiment for assessing the tolerance of the ¹⁸F-fluorodeboronation towards heterocycles, and the use of this method to guide the retro-radiosynthesis of heterocycle-rich, medicinally relevant molecules.

Chapter 4 contains synthetic procedures and characterisation data for compounds in Chapters 2 and 3.

Authors: Taylor, N

• DOI: 10.5287/ora-o8rxgdapn
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Positron Emission Tomogrphy; 18F-Radiolabelling; 18F-Fluorination; [18F]Fluoroarenes; Copper; PET
• Subjects: Tomography, Emission; Fluorination