The traceless Staudinger ligation for indirect 18F-radiolabelling

Area of Science:

• Radiochemistry
• Organic Synthesis
• Chemical Biology

Background:

• The Staudinger ligation is a bioorthogonal reaction widely used in chemical biology.
• Radiofluorination, particularly with fluorine-18 (18F), is crucial for developing Positron Emission Tomography (PET) imaging agents.
• Efficient and high-yielding methods for incorporating 18F into molecules are in high demand.

Purpose of the Study:

• To develop a novel Staudinger radio-ligation method for 18F-labeling.
• To achieve high radiochemical yields in the synthesis of 18F-labeled molecules.
• To introduce and validate a fluorous variant of the Staudinger radio-ligation for potential applications in purification or specialized labeling.

Main Methods:

• The study employed the Staudinger ligation between phosphine-substituted thioesters and 18F-fluoroethylazide.
• Optimization of reaction conditions to maximize radiochemical yield.
• Validation of a fluorous modification to the Staudinger radio-ligation approach.

Main Results:

• The developed Staudinger radio-ligation successfully produced 18F-labeled molecules.
• Radiochemical yields consistently surpassed 95%.
• The first fluorous variant of the Staudinger radio-ligation was successfully validated.

Conclusions:

• The Staudinger ligation offers a highly efficient route for 18F-labeling.
• The high yields achieved are advantageous for the synthesis of radiopharmaceuticals.
• The validated fluorous Staudinger radio-ligation expands the toolkit for radiolabeling and purification strategies.