Chemistry of fluorinated purines

Fluorinated purines and related nucleosides exhibit a diverse range of biological activities. The presence of a single fluoro or trifluoromethyl group at the 2-, 6-, or 8-position of a purine or purine nucleoside, or combinations of multiple substitutions at these positions, can confer advantageous changes to physicochemical, metabolic and biological properties. The incorporation of an 18 F label into purine nucleosides provides tools for in vivo imaging by positron emission tomography (PET). In this chapter we outline the many synthetic routes, both well established and more unusual, that are available for the selective preparation of 2-, 6-, or 8-substituted fluorinated purines, and the extension of these methods to make derivatives fluorinated at specific combinations of these positions. Applications of fluorinated purines in biomedical research are highlighted. The reactions of fluorinated purines are also summarised, in particular the range of nucleophilic displacements that make the molecules useful as synthetic intermediates for medicinal chemistry and reagents for chemical biology studies.