Late stage benzylic C-H fluorination with [¹⁸F]fluoride for PET imaging.
We describe the first late-stage (18)F labeling chemistry for aliphatic C-H bonds with no-carrier-added [(18)F]fluoride. The method uses Mn(salen)OTs as an F-transfer catalyst and enables the facile labeling of a variety of bioactive molecules and building blocks with radiochemical yields (RCY) ranging from 20% to 72% within 10 min without the need for preactivation of the labeling precursor. Notably, the catalyst itself can directly elute [(18)F]fluoride from an ion exchange cartridge with over 90% efficiency. Using this feature, the conventional and laborious dry-down step prior to reaction is circumvented, greatly simplifying the mechanics of this protocol and shortening the time for automated synthesis. Eight drug molecules, including COX, ACE, MAO, and PDE inhibitors, have been successfully [(18)F]-labeled in this way.
Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States.
Xiongyi
X
Huang
Wei
W
Liu
Hong
H
Ren
Ramesh
R
Neelamegam
Jacob M
JM
Hooker
John T
JT
Groves
D002384:Catalysis; D005029:Ethylenediamines / Q000737:chemistry; D005459:Fluorides / Q000138:chemical synthesis / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry; D054879:Halogenation; D008345:Manganese / Q000737:chemistry; D008958:Models, Molecular; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*
D005029:Ethylenediamines; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D008345:Manganese; C011452:disalicylaldehyde ethylenediamine; D005459:Fluorides