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The availability of radiolabelled probes is important for in vivo studies by positron emission tomography (PET). Among the frontier challenges in 18F-radiochemistry are the interconnected goals of increasing synthetic efficiency and diversity in the construction of 18F-labelled radiotracers. 18F-Radioretrosynthetic strategies implemented to date are typically linear sequences of transformations designed with the aim of introducing the 18F-label ideally in the last step or at least as late as possible. Here we report that convergent 18F-radiochemistry allows for the rapid assembly of functionalised 18F-radiotracers from readily accessible 18F-labelled prosthetic groups. Using multicomponent reactions for proof of concept, Ugi-4CR, Passerini-3CR, Biginelli-3CR and Groebke-3CR were performed successfully using 18F-benzaldehydes and these highly convergent reactions delivered, in high radiochemical yield (RCY), structurally complex 18F-radiotracers with the label positioned on an aryl motif not responsive to direct nucleophilic fluorination. These data establish an unprecedented connection between radiochemistry for PET and the field of multicomponent chemistry and demonstrate that convergent retroradiosynthesis is a powerful strategy expanding dramatically the scope of 18F-prosthetic group radiochemistry. The preparation of 18F-labelled prosthetic groups from [18F]fluoride ion is commonly performed in many labelling laboratories, so the concept of convergent 18F-radiosynthesis can easily be applied immediately.
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