MCR Scaffolds Get Hotter with ¹⁸F-Labeling

Area of Science:

• Radiochemistry and Medicinal Chemistry
• Development of novel radiotracers for molecular imaging
• Application of multicomponent reactions (MCRs) in drug discovery

Background:

• Positron emission tomography (PET) is crucial for drug development and diagnostics, but efficient synthesis of radiolabeled compounds remains a challenge.
• Multicomponent reactions (MCRs) allow for the rapid synthesis of diverse, drug-like molecules.
• Combining PET labeling with MCRs can streamline radioanalytical and imaging studies.

Purpose of the Study:

• To develop and optimize robust on-site radiolabeling conditions for MCR-synthesized scaffolds.
• To demonstrate the applicability of the method across various drug-like molecular structures.
• To facilitate the synthesis of novel PET imaging agents.

Main Methods:

• Optimization of copper-mediated oxidative ¹⁸F-fluorination conditions.
• Application of the optimized method to diverse MCR scaffolds including arenes, β-lactam, tetrazole, and oxazole.
• Synthesis of labeled compounds via pinacol-derived aryl boronic esters (arylBPin).

Main Results:

• Successful development of robust on-site radiolabeling conditions.
• Achieved radiochemical conversions (RCCs) ranging from 15% to 76% for various scaffolds.
• Demonstrated the versatility of the method for synthesizing structurally different, drug-like molecules.

Conclusions:

• The developed method offers a simplified approach to synthesizing ¹⁸F-labeled compounds for PET imaging.
• This strategy effectively combines MCRs with efficient radiolabeling, accelerating the development of diagnostic agents.
• The optimized on-site radiolabeling is applicable to a range of biologically relevant scaffolds.