Abstract
The 18F-labeling of CF2H groups has been recently studied in radiopharmaceutical chemistry owing to the favorable nuclear and physical characteristics of the radioisotope 18F for positron emission tomography (PET). Following up on the reported efficiency of the [18F]difluoromethyl benzothiazolyl-sulfone ([18F]1) as a 18F-difluoromethylating reagent, we investigated the influence of structurally-related [18F]difluoromethyl heteroaryl-sulfones in the reactivity toward the photoredox C–H 18F-difluoromethylation of heteroarenes under continuous-flow conditions. In the present work, six new [18F]difluoromethyl heteroaryl-sulfones [18F]5a–[18F]5f were prepared and, based on the overall radiochemical yields (RCYs), three of these reagents ([18F]5a, [18F]5c, and [18F]5f) were selected for the fully automated radiosynthesis on a FASTlabTM synthesizer (GE Healthcare) at high level of starting radioactivity. Subsequently, their efficiency as 18F-difluoromethylating reagents was evaluated using the antiherpetic drug acyclovir as a model substrate. Our results showed that the introduction of molecular modifications in the structure of [18F]1 influenced the amount of fac-IrIII(ppy)3 and the residence time needed to ensure a complete C–H 18F-difluoromethylation process. The photocatalytic C–H 18F-difluoromethylation reaction with the reagents [18F]5a, [18F]5c, and [18F]5f was extended to other heteroarenes. Radical-trapping experiments demonstrated the likely involvement of radical species in the C–H 18F-difluoromethylation process.
Highlights
The fluorine-18 (18 F) isotope has been regarded the “radionuclide of choice” due to its suitable physical and nuclear features for in vivo positron emission tomography (PET) imaging in living subjects [1,2,3,4]
We initially performed the organic synthesis of the difluoromethyl heteroaryl-sulfones 5a–5f as prepare the difluoromethyl heteroaryl-sulfones 5a–5f, we considered a two-step procedure involving non-radioactive standards for confirmation of the identity of the 18F-labeled compounds
The difluoromethylation of the heteroaryl-thiols 3a–3f to afford the difluoromethyl heteroarylInspired by the methodologies formerly described by Akita [46] and Jubault [47], the sulfides 4a–4f
Summary
The fluorine-18 (18 F) isotope has been regarded the “radionuclide of choice” due to its suitable physical and nuclear features for in vivo positron emission tomography (PET) imaging in living subjects [1,2,3,4]. PET technology has proven highly valuable in the observation of biochemical and physiological changes that may take place before the anatomical alterations of a certain disease are detected [5,6,7,8]. The suitability of the 18 F radioisotope in Catalysts 2020, 10, 275; doi:10.3390/catal10030275 www.mdpi.com/journal/catalysts. Among the 10,existent motifs, the difluoromethyl (CF2 H) group has attracted considerable attention in medicinal chemistry due to its lipophilic hydrogen-bond donor anatomical alterations of a certain disease are detected [5,6,7,8]. The suitability of the 18F radioisotope in properties
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
