Chelator-Accelerated One-Pot ‘Click’ Labeling of Small Molecule Tracers with 2-[18F]Fluoroethyl Azide
| Autor: | Bent W. Schoultz, Matthias J. Koepp, Erik Årstad, Eva Galante |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
2-[18F]fluoroethyl azide
1 2 3-Triazole Pharmaceutical Science 010402 general chemistry 01 natural sciences automated synthesis Analytical Chemistry lcsh:QD241-441 chemistry.chemical_compound lcsh:Organic chemistry Drug Discovery Nucleophilic substitution BPDS Organic chemistry Physical and Theoretical Chemistry Fluoroethyl 010405 organic chemistry Organic Chemistry Combinatorial chemistry radiotracer Cycloaddition 0104 chemical sciences PET chemistry Chemistry (miscellaneous) Reagent Yield (chemistry) 6-halopurine click chemistry Click chemistry fluorine-18 Molecular Medicine Azide 1 2 3-triazole |
| Zdroj: | Molecules Volume 18 Issue 5 Pages: 5335-5347 Molecules, Vol 18, Iss 5, Pp 5335-5347 (2013) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules18055335 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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