Synthesis of 18F‐labeled Aryl Trifluoromethyl Sulfones, ‐Sulfoxides, and ‐Sulfides for Positron Emission Tomography

• Published in: Angewandte Chemie 2024-07, Vol.136 (27), p.n/a
• Main Authors: Veth, Lukas, Windhorst, Albert D., Vugts, Danielle J.
• Format: Article
• Language: English
• Subjects: Aromatic compounds; Bioactive compounds; Biological activity; Fluorides; Fluorine isotopes; fluorine-18; Functional groups; isotopic labeling; Nuclear medicine; PET; Positron emission; Positron emission tomography; radiochemistry; Radiolabelling; Reagents; Sulfides; Sulfones; Sulfoxides; Tomography; Tracers; trifluoromethylation
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202404278

Positron emission tomography (PET) is becoming increasingly important in nuclear medicine and drug discovery. To date, the development of many potential PET tracers is hampered by the lack of suitable synthetic pathways for their preparation. This is particularly true for the highly desired radiolabeling of compounds bearing [18F]CF3‐groups. For instance, S(O)nCF3‐groups (n=0, 1, 2) serve as structural motif in a range of biologically active compounds, but their radiosynthesis remains largely unprecedented (for n=1, 2). Herein, we describe general methods for the radiosynthesis of 18F‐labeled aryl trifluoromethyl sulfones, ‐sulfoxides, and ‐sulfides. All three methods are operationally straightforward, start from widely available precursors, i.e., sulfonyl fluorides and thiophenols, and make use of the recently established [18F]Ruppert‐Prakash reagent. Further, the syntheses display good functional group tolerance as demonstrated by the 18F‐labeling of more than 40 compounds. The applicability of the new method is demonstrated by the radiolabeling of three bioactive molecules, optionally to be used as PET tracers. In a broader context, this work presents a substantial expansion of the chemical space of radiofluorinated structural motifs to be used for the development of new PET tracers. The mild and high‐yielding synthesis of 18F‐labeled aryl trifluoromethyl sulfones, ‐sulfoxides, and ‐sulfides using [18F]Ruppert‐Prakash reagent is described. The application to the radiolabeling of different bioactive compounds using >1 GBq of 18F‐labeling reagent is demonstrated. This work expands the radiochemical space of [18F]CF3‐containing structural motifs for the use in positron emission tomography.