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Rapid Electrophilic 211At-Astatination of Trimethylgermyl Arenes
Marius Müller1,2, Umberto Maria Battisti1, Merlin Zabrocki1
1Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Abstract:
A set of 211At-astatoarenes were synthesized from corresponding trimethylgermyl arenes with an average radiochemical conversion (RCC) of ca. 50 % for electron-rich and approx. 70 % in case of electron-deficient arenes. Both electron rich and electron poor substrates were successfully radiolabeled at room temperature (RT) using relatively low precursor amounts (0.15 μmol/0.02 mL solvent (7.5 mM)). Ready access to ortho-, para- and meta- astatinated arenes was achievable. Optimized reaction conditions were successfully applied to label a poly (ADP-ribose) polymerase (PARP) inhibitor with a RCC of approx. 50 %. We believe that trimethylgermyl derivatives are a viable addition to the astatination precursor toolbox and facilitate astatination of arenes. The developed labeling method should easily be applicable for productions under good manufacturing practice (GMP).
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