A Multistep, One-Pot Bismuth-Mediated Radiohalogenation Method for Preparation of Radiopharmaceuticals for Imaging...

Area of Science:

• Medicinal Chemistry
• Radiochemistry
• Organic Synthesis

Background:

• (Radio)haloaromatic compounds are crucial in drug discovery and radiopharmaceuticals.
• Efficient synthesis of these compounds, especially for electron-deficient or hindered rings, remains a challenge.
• Existing methods often struggle with stoichiometric deficiency of halides.

Purpose of the Study:

• To develop a rapid, efficient, and regioselective radiohalogenation method.
• To address the need for synthesizing (radio)haloaromatic compounds with diverse electronic and steric properties.
• To demonstrate the utility of the method for preparing radiopharmaceuticals.

Main Methods:

• Regioselective bismuth-mediated radiohalogenation of arylboronates.
• Utilized a wide range of functional groups and aromatic ring types (electron-rich, -deficient, -neutral, sterically crowded).
• Applied the method to synthesize radiolabeled derivatives of radiopharmaceuticals, including a PSMA inhibitor.

Main Results:

• Achieved excellent radiochemical conversion (80-99%) and purity (>99%).
• Obtained high radiochemical yields (42-78%) for 77Br-, 124I-, and 211At-labeled compounds.
• Demonstrated high molar activities (>250 GBq/μmol) for radiolabeled radiopharmaceuticals.

Conclusions:

• The developed bismuth-mediated method is convenient and effective for synthesizing (radio)haloaromatic compounds.
• The method is suitable for a broad scope of aromatic substrates, including challenging ones.
• This approach is highly promising for the clinical application of radiopharmaceuticals.