Mawick M, Jaworski C, Bittermann J, Iovkova L, Pu Y, Wängler C, Wängler B, Jurkschat K, Krause N, Schirrmacher R (2023) CycloSiFA: The Next Generation of Silicon-Based Fluoride Acceptors for Positron Emission Tomography (PET). Angewandte Chemie International Edition, 62(50), e202309002. DOI: 10.1002/anie.202309002.
Cyclic azasilole derivatives undergo ring-opening with 18F– anions under mild conditions and with high radiochemical yield. They represent a novel class of Silicon Fluoride Acceptor systems (CycloSiFA) and hold great potential for convenient kit-like labelling procedures in different medicinal applications.
The ring-opening Si-fluorination of a variety of azasilole derivatives cyclo-1-(iPr2Si)−4-X−C6H3−2-CH2NR (4: R=2,6-iPr2C6H3, X=H; 4 a: R=2,4,6-Me3C6H2, X=H; 9: R=2,6-iPr2C6H3, X=tBuMe2SiO; 10: R=2,6-iPr2C6H3, X=OH; 13: R=2,6-iPr2C6H3, X=HCCCH2O; 22: R=2,6-iPr2C6H3, X=tBuMe2SiCH2O) with different 19F-fluoride sources was studied, optimized and the experience gained was used in a translational approach to create a straightforward 18F-labelling protocol for the azasilole derivatives [18F]6 and [18F]14. The latter constitutes a potential clickable CycloSiFA prosthetic group which might be used in PET tracer development using Cu-catalysed triazole formation. Based on our findings, CycloSiFA has the potential to become a new entry into non-canonical labelling methodologies for radioactive PET tracer development.