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Molecules 2013, 18(5), 5335-5347; doi:10.3390/molecules18055335
Article

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

1
, 2
, 3
 and 1,*
1 Department of Chemistry and Institute of Nuclear Medicine, University College London, 235 Euston Road (T-5), London, NW1 2BU, UK 2 Department of Chemistry, University of Oslo, PO Box 1033, Blindern N-0315, Oslo, Norway 3 Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, 33 Queen Square, London, WC1N 3BG, UK
* Author to whom correspondence should be addressed.
Received: 8 April 2013 / Revised: 16 April 2013 / Accepted: 3 May 2013 / Published: 10 May 2013
(This article belongs to the Special Issue PET Chemistry in Molecular Imaging)
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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.
Keywords: fluorine-18; click chemistry; BPDS; 2-[18F]fluoroethyl azide; 6-halopurine; automated synthesis; 1,2,3-triazole; PET; radiotracer fluorine-18; click chemistry; BPDS; 2-[18F]fluoroethyl azide; 6-halopurine; automated synthesis; 1,2,3-triazole; PET; radiotracer
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Galante, E.; Schoultz, B.W.; Koepp, M.; Årstad, E. Chelator-Accelerated One-Pot ‘Click’ Labeling of Small Molecule Tracers with 2-[18F]Fluoroethyl Azide. Molecules 2013, 18, 5335-5347.

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