The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click-type reaction, was used to label a double-stranded oligonucleotide (siRNA) with fluorine-18. An alkyne solid support CPG for the preparation of monostranded oligonucleotides functionalized with alkyne has been developed. Two complementary azide labeling agents (1-(azidomethyl)-4-[(18)F]fluorobenzene) and 1-azido-4-(3-[(18)F]fluoropropoxy)benzene have been produced with 41% and 35% radiochemical yields (decay-corrected), respectively. After annealing with the complementary strand, the siRNA was directly labeled by click chemistry with [(18)F]fluoroazide to produce the [(18)F]-radiolabeled siRNA with excellent radiochemical yield and purity.
![4-[2-[(E)-2-[(3Z)-3-[(2Z)-2-[3,3-dimethyl-1-(4-sulfobutyl)indol-2-ylidene]ethylidene]-2-(prop-2-ynylamino)cyclopenten-1-yl]ethenyl]-3,3-dimethylindol-1-ium-1-yl]butane-1-sulfonate Structure](https://image.chemsrc.com/caspic/187/1188292-54-7.png)