211 At and 125 I-Labeling of (Hetero)Aryliodonium Ylides: Astatine Wins Again

• Published in: Chemistry : a European journal 2022-02, Vol.28 (11), p.e202104169-e202104169
• Main Authors: Maingueneau, Clémence, Berdal, Marion, Eychenne, Romain, Gaschet, Joëlle, Chérel, Michel, Gestin, Jean-François, Guérard, François
• Format: Article
• Language: English
• Subjects: Astatine - chemistry; Iodine Radioisotopes - chemistry; Pharmaceutical Preparations; Radiopharmaceuticals - chemistry
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202104169

Despite the growing interest in radioiodine and At-labeled radiopharmaceuticals, the search for radiolabeling reactions has been somewhat neglected, resulting in a limited number of available radiosynthetic strategies. Herein we report a comparative study of nucleophilic I and At-labeling of aryliodonium ylides. Whereas radioiodination efficiency was low, At-labeling performed efficiently on a broad scope of precursors. The most activated aryliodonium ylides led rapidly to quantitative reactions at room temperature in acetonitrile. For deactivated precursors, heating up to 90 °C in glyme and addition of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as radical scavenger appeared essential to avoid precursor degradation and to achieve high radiochemical yields and molar activity. The approach was applied successfully to the preparation of 4-[ At]astatophenylalanine (4-APA), an amino acid derivative increasingly studied as radiotherapeutic drug for cancers. This validated aryliodonium ylides as a valuable tool for nucleophilic At-labeling and will complement the short but now growing list of available astatination reactions.