Intramolecular Friedel-Crafts Acylation of [11C]Isocyanates Enabling the Radiolabeling of [carbonyl-11C]DPQ.

Marius Ozenil, Lukas Kogler, Braeden A Mair, Marcus Hacker, Wolfgang Wadsak, Benjamin H Rotstein, Verena Pichler

Chemistry (Weinheim an der Bergstrasse, Germany) 2024 May 17

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α,β-aromatic lactams are highly abundant in biologically active molecules, yet so far they cannot be radiolabeled with short-lived (t1/2=20.3 min), β+-decaying carbon-11, which has prevented their application as positron emission tomography tracers. Herein, we developed, optimized, and applied a widely applicable, one-pot, quick, robust and automatable radiolabeling method for α,β-aromatic lactams starting from [11C]CO2 using the reagent POCl3⋅AlCl3. This method proceeds via intramolecular Friedel-Crafts acylation of in situ formed [11C]isocyanates and shows a broad substrate scope for the formation of five- and six-membered rings. We implemented our developed labeling method for the radiosynthesis of the potential PARP1 PET tracer [carbonyl-11C]DPQ in a clinical radiotracer production facility following the standards of the European Pharmacopoeia. © 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.

Citation

Marius Ozenil, Lukas Kogler, Braeden A Mair, Marcus Hacker, Wolfgang Wadsak, Benjamin H Rotstein, Verena Pichler. Intramolecular Friedel-Crafts Acylation of [11C]Isocyanates Enabling the Radiolabeling of [carbonyl-11C]DPQ. Chemistry (Weinheim an der Bergstrasse, Germany). 2024 May 17;30(28):e202400581