A protocol for controlled reactivity shift in the 2,2-difluorovinyl motif used for selective S–18F and C–18F bond formation.

Autor: Maqbool, Mudasir, Jakobsson, Jimmy Erik, Alluri, Santosh Reddy, Kramer, Vasko, Riss, Patrick Johannes
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Zdroj: Communications Chemistry; 4/29/2024, Vol. 7 Issue 1, p1-6, 6p
Abstrakt: Positron emission tomography (PET) is a powerful imaging technique for biomedical research, drug development and medical diagnosis. The power of PET lies in biochemically selective radiotracers, labelled with positron emitters like fluorine-18 image chemical processes in vivo. A rapid and remarkably efficient, unprecedented protocol to select between S-F and C-F bond formation based on activation of 1,1-difluoroethylene groups followed by selective oxidation or reduction is described. While transition metal mediated conditions can be employed, the reaction proceeds in high yield using unobjectionable chemical reagents amenable to routine radiotracer production. The latter bodes well for facile clinical translation of the method. The new technique affords radiotracers and the labelling reagent 2,2-difluoro-2-(fluoro-18F)ethyl 4-methylbenzenesulfonate ([18F]1b) in excellent yield. Following oxygenation of the reaction mixture with medical oxygen or air, sulfonyl fluorides are obtained as the primary product. The new protocol was employed in a proof of principle to develop a radiometric assay for quantitation of sulfonylation yield with sulfonyl fluoride reagents. With operational ease and mild conditions, the method bodes a high potential for radiolabelling of biomolecules, known enzyme inhibitors and other temperature-sensitive compounds. The fluorine isotope 18F is a PET nuclide used for imaging studies, but the incorporation of [18F]HF into 2,2-difluorovinyl groups to generate radiotracers and labeling reagents has only been achieved in low yields. Here, using a combination of Et3SiH and TEMPO in the absence of oxidizing agents is shown to afford a higher yield, better product quality, and controllable selectivity between the formation of a S–F or C–F bond. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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