title: Chelator-accelerated one-pot 'click' labeling of small molecule tracers with 2-[¹⁸F]fluoroethyl azide.
abstract: 2-[¹⁸F]Fluoroethyl azide ([¹⁸F]FEA) can readily be obtained by nucleophilic substitution of 2-azidoethyl-4-toluenesulfonate with [¹⁸F]fluoride (half-life 110 min), and has become widely used as a reagent for 'click' labeling of PET tracers. However, distillation of [18F]FEA is typically required, which is time-consuming and unpractical for routine applications. In addition, copper(I)-catalyzed cycloaddition of [¹⁸F]FEA with non-activated alkynes, and with substrates containing labile functional groups, can be challenging. Herein, we report a highly efficient and practical ligand-accelerated one-pot/two-step method for 'click' labeling of small molecule tracers with [¹⁸F]FEA. The method exploits the ability of the copper(I) ligand bathophenanthrolinedisulfonate to accelerate the rate of the cycloaddition reaction. As a result, alkynes can be added directly to the crude reaction mixture containing [¹⁸F]FEA, and as cyclisation occurs almost immediately at room temperature, the reaction is tolerant to labile functional groups. The method was demonstrated by reacting [¹⁸F]FEA with a series of alkyne-functionalized 6-halopurines to give the corresponding triazoles in 55-76% analytical radiochemical yield.
authors.affiliation: Department of Chemistry and Institute of Nuclear Medicine, University College London, 235 Euston Road, T-5, London NW1 2BU, UK.
authors.forename: Eva
authors.initials: E
authors.lastname: Galante
authors.forename: Bent Wilhelm
authors.initials: BW
authors.lastname: Schoultz
authors.forename: Matthias
authors.initials: M
authors.lastname: Koepp
authors.forename: Erik
authors.initials: E
authors.lastname: Arstad
mesh_terms: D001386:Azides / Q000737:chemistry*; D002384:Catalysis; D057930:Click Chemistry / Q000379:methods*; D003300:Copper / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D001386:Azides; D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated; D003300:Copper