"Click labeling" with 2-[18f]fluoroethylazide for positron emission tomography.
As an effort in the development of more flexible (18)F-labeling chemistry, we report herein on the use of the Cu(I)-catalyzed Huisgen cycloaddition, also known as the "click reaction", to form (18)F-labeled 1,2,3-triazoles. Nucleophilic fluorination of 2-azidoethyl-4-toluenesulfonate followed by distillation provided 2-[(18)F]fluoroethylazide in 55% radiochemical yield (decay-corrected). 2-[(18)F]fluoroethylazide was reacted with a small library of terminal alkynes in the presence of excess Cu(2+)/ascorbate or copper powder. The most reactive alkyne, N-benzylpropynamide provided nearly quantitative incorporation of 2-[(18)F]fluoroethylazide after 15 min at ambient temperature, whereas the majority of the alkyne substrates provided excellent yields of the corresponding (18)F-labeled 1,2,3-triazoles following heating to 80 degrees C. Using the method described, a model peptide was obtained in 92.3 +/- 0.3% (n = 3) radiochemical yield (decay-corrected) after purification by semipreparative HPLC.
Glaser
Matthias
M
Hammersmith Imanet Ltd, Cyclotron Building, Du Cane Road, London W12 ONN, UK.
Arstad
Erik
E
D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry*; D001557:Benzenesulfonates / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D010455:Peptides / Q000737:chemistry*; D049268:Positron-Emission Tomography; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry
C522267:2-azidoethyl-4-toluenesulfonic acid; C522266:2-fluoroethylazide; D000480:Alkynes; D001386:Azides; D001557:Benzenesulfonates; C522268:N-benzylpropynamide; D010455:Peptides; D014230:Triazoles; D003300:Copper