Organomediated approaches to 18F-radiochemistry for PET

Thesis

This thesis has focussed on ¹⁸F-fluorination reactions activated by an organomediator, with the aim of broadening the scope of metal-free reactions in ¹⁸F-radiosynthesis.

Chapter 1 provides an introduction to positron emission tomography (PET) and ¹⁸Fradiochemistry, including radioisotope production and modes of activation in ¹⁸Fradiosynthesis.

In Chapter 2, the concept of chirality and its relevance in the context of radiotracer design is introduced. The previously disconnected fields of organomediated asymmetric fluorination and ¹⁸F-radiosynthesis are merged for the first time via investigation of three distinct activation modes: chiral non-racemic secondary amine-mediated asymmetric α-¹⁸F-fluorination of aldehydes employing [¹⁸F]N-fluorobenzenesulfonimide; use of a phase transfer reagent for asymmetric ¹⁸F-fluorocyclisation and application of a chiral nonracemic ¹⁸F-fluorinating agent, chiral [¹⁸F]Selectfluor bis-triflate. Application of the first of these approaches to the radiosynthesis of the PET tracer (2S,4S)-4-[¹⁸F]fluoroglutamic acid with high d.r. is described.

Chapter 3 explores the use of hypervalent iodine reagents to mediate the oxidative fluorination of N-arylsulfonamides with nucleophilic fluoride via an umpolung approach. Preliminary studies on translation to radiosynthesis with [¹⁸F]fluoride are also disclosed.

In Chapter 4, experimental data is provided for all compounds, as well as analytical and chiral HPLC traces for ¹⁸F-reactions.

Authors: Buckingham, F

• DOI: 10.5287/ora-6rxozrzvj
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Keywords: organomediated; 18F; radiochemistry; asymmetric; fluorination