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Chelator-Accelerated One-Pot ‘Click’ Labeling of Small Molecule Tracers with 2-[(18)F]Fluoroethyl Azide

2-[(18)F]Fluoroethyl azide ([(18)F]FEA) can readily be obtained by nucleophilic substitution of 2-azidoethyl-4-toluenesulfonate with [(18)F]fluoride (half-life 110 min), and has become widely used as a reagent for ‘click’ labeling of PET tracers. However, distillation of [(18)F]FEA is typically requ...

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Detalles Bibliográficos
Autores principales: Galante, Eva, Schoultz, Bent Wilhelm, Koepp, Matthias, Årstad, Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270487/
https://www.ncbi.nlm.nih.gov/pubmed/23666002
http://dx.doi.org/10.3390/molecules18055335
Descripción
Sumario:2-[(18)F]Fluoroethyl azide ([(18)F]FEA) can readily be obtained by nucleophilic substitution of 2-azidoethyl-4-toluenesulfonate with [(18)F]fluoride (half-life 110 min), and has become widely used as a reagent for ‘click’ labeling of PET tracers. However, distillation of [(18)F]FEA is typically required, which is time-consuming and unpractical for routine applications. In addition, copper(I)-catalyzed cycloaddition of [(18)F]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 [(18)F]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 [(18)F]FEA, and as cyclisation occurs almost immediately at room temperature, the reaction is tolerant to labile functional groups. The method was demonstrated by reacting [(18)F]FEA with a series of alkyne-functionalized 6-halopurines to give the corresponding triazoles in 55–76% analytical radiochemical yield.