Rapid Electrophilic 211At‐Astatination of Trimethylgermyl Arenes

• Published in: ChemPlusChem (Weinheim, Germany) Vol. 89; no. 9; pp. e202400254 - n/a
• Main Authors: Müller, Marius, Battisti, Umberto Maria, Zabrocki, Merlin, Hansson, Ellinor, Jensen, Holger, Aneheim, Emma, Lindegren, Sture, Herth, Matthias Manfred
• Format: Journal Article
• Language: English
• Published: 01.09.2024
• Subjects: Astatine-211; Chemical Sciences; Electrophilic Aromatic Substitution; Kemi; Radiopharmaceuticals; Trifluoro Acetic Acid; Trimethylgermyl Arenes
• DOI: 10.1002/cplu.202400254
• ISSN: 2192-6506

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). 211At‐Astatodegermylation: Different ortho‐, meta‐, and para‐substituted trimethylgermyl arenes were astatinated at low precursor amounts (0.15 μmol) in trifluoroacetic acid with an average radiochemical conversion (RCC) of ca. 50 % for electron‐rich and approx. 70 % in case of electron‐deficient arenes.