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211 At and 125 I‐Labeling of (Hetero)Aryliodonium Ylides: Astatine Wins Again
Author(s) -
Maingueneau Clémence,
Berdal Marion,
Eychenne Romain,
Gaschet Joëlle,
Chérel Michel,
Gestin JeanFrançois,
Guérard François
Publication year - 2022
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202104169
Subject(s) - chemistry , scavenger , nucleophile , acetonitrile , nucleophilic substitution , radiochemistry , derivative (finance) , combinatorial chemistry , medicinal chemistry , radical , organic chemistry , catalysis , financial economics , economics
Despite the growing interest in radioiodine and 211 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 125 I and 211 At‐labeling of aryliodonium ylides. Whereas radioiodination efficiency was low, 211 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‐[ 211 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 211 At‐labeling and will complement the short but now growing list of available astatination reactions.