MCR Scaffolds Get Hotter with (18)F-Labeling

Imaging techniques, such as positron emission tomography (PET), represent great progress in the clinical development of drugs and diagnostics. However, the efficient and timely synthesis of appropriately labeled compounds is a largely unsolved problem. Numerous small drug-like molecules with high structural diversity can be synthesized via convergent multicomponent reactions (MCRs). The combination of PET labeling with MCR synthesis of biologically active compounds can greatly simplify radioanalytical and imaging-based analysis. In a proof-of-concept study, we optimized robust on-site radiolabeling conditions that were subsequently applied to several structurally different drug-like MCR scaffolds (e.g., arenes, β-lactam, tetrazole, and oxazole). These labeled scaffolds were synthesized via pinacol-derived aryl boronic esters (arylBPin) by copper-mediated oxidative (18)F-fluorination with radiochemical conversions (RCCs) from 15% to 76%.