Investigation of fluorination methodologies for application in positron emission tomography

Abstract

The use of fluorinated compounds has become increasingly popular within recent decades, especially within the fields of pharmaceuticals, agrochemicals, and fine chemicals. Incorporation of fluorine into a compound has various effects on the chemical properties of a molecule. In the pharmaceutical industry, around 20% of the commercially available pharmaceuticals contain fluorinea . Fluorine incorporation has profound effects on the pharmacokinetics and physiochemical properties of a compound, such as the adsorption, distribution, and increased metabolic stability. An emerging area of fluorine chemistry is the application of the unnatural isotope fluorine-18 in radiochemical labelling for positron emission tomography (PET). PET is a non-invasive nuclear imaging technique that is used to observe biological and physiological functions in the body, including blood flow, metabolism and to probe disease progression. Fluorine-18 is the most clinically relevant radioisotope for PET imaging; however the universal uptake of PET is limited and there is an urgent unmet clinical need to expand the range of the fluoro-radiopharmaceuticals that are readily available and open the way for the benefits that the power medical imaging offers in the diagnosis and management of disease. The work herein describes the investigation into a nucleophilic and electrophilic fluorination methodology. The study of an iron (II) acetylacetonate initiated electrophilic fluorination method led to the discovery of a practical route to the thiodifluoromethylene group using SelectfluorTM. Subsequent mechanistic investigation has allowed the synthesis of a number of difluorinated compounds in moderate to excellent yields.