Organomediated approaches to 18F-radiochemistry for PET

Description

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. <b>Chapter 1</b> provides an introduction to positron emission tomography (PET) and ¹⁸Fradiochemistry, including radioisotope production and modes of activation in ¹⁸Fradiosynthesis. In <b>Chapter 2</b>, 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 &alpha;-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. <b>Chapter 3</b> 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 <b>Chapter 4</b>, experimental data is provided for all compounds, as well as analytical and chiral HPLC traces for ¹⁸F-reactions.

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1. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730496

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Additional Fields

Identifer	oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:730496
Date	January 2015
Creators	Buckingham, Faye
Contributors	Gouverneur, Véronique
Publisher	University of Oxford
Source Sets	Ethos UK
Detected Language	English
Type	Electronic Thesis or Dissertation
Source	https://ora.ox.ac.uk/objects/uuid:00774f21-9abf-4a4a-b4d3-1300e3ae3fa1