Scheme: Wolfson Research Merit Awards
Organisation: University of Oxford
Dates: Oct 2013-Sep 2018
Summary: The impact of fluorine chemistry in the life sciences is enormous. As many as 30-40% of agrochemicals and 20% of pharmaceuticals on the market are estimated to contain fluorine, and developmental pipelines are predicted to contain more. Fluorine substitution affects nearly all physicochemical and adsorption, distribution, metabolism and excretion properties of a lead compound. Moreover, systematic fluorine scans of ligands is becoming a powerful approach to strenghthen protein-ligand binding interactions, one of the key aspects of lead optimisations. 19F- and 18F-labelled compounds are finding increasing use in imaging for Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET), respectively. These applications demand strategies for the selective installation of F-substituent on complex targets upon manipulation of feedstock functional groups. Our research program may be divided into two broad categories: (1) Chemical Advances for the synthesis of structurally and biologically compelling small fluorinated molecules for applications in medicinal chemistry, and (2) Radiochemical Advances for the production of [18F]labelled biomarkers for applications in PET. Such advances are crucial to interrogate molecular interactions in organisms using radioemission imaging methods and to develop new synthetic [18F]labelled (bio)molecules tools to diagnose, monitor and treat diseases. Over the course, of the year, we have developed new biomimetic reagents for nucleophilic fluorination, novel synthetic and catalytic methods for late stage fluorination, and novel radiochemistry to streamline access to novel radiotracers to be used in molecular imaging (PET).