Iron-Catalyzed Batch/Continuous Flow C-H Functionalization Module for the Synthesis of Anticancer Peroxides

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Peroxides are valuable functional groups in organic synthesis and medicinal chemistry.
• Developing efficient and selective methods for peroxide synthesis remains a challenge.

Purpose of the Study:

• To develop a novel iron-catalyzed dehydrogenative cross-coupling reaction for peroxide synthesis.
• To synthesize and evaluate a library of novel peroxides derived from biologically relevant scaffolds.

Main Methods:

• Iron-catalyzed reaction of carbonyl compounds with aliphatic peroxides under mild conditions.
• Synthesis of diverse linear alkylated and arylated peroxides.
• Mechanistic studies involving redox processes and radical intermediates.
• Anticancer activity evaluation using cell viability assays.

Main Results:

• Successful synthesis of a library of peroxides in good to excellent yields.
• High selectivity and functional group tolerance observed for biologically important derivatives (2-oxindole, barbituric acid, 4-hydroxy coumarin).
• Scalable synthesis demonstrated, including continuous flow capability with enhanced safety.
• Identified peroxides exhibiting significant anticancer activity with a minimum IC50 of 5.3 μM.

Conclusions:

• The developed iron-catalyzed method provides an efficient and versatile route to novel peroxides.
• The synthesized peroxides demonstrate potent anticancer properties, highlighting their therapeutic potential.
• The reaction's scalability and safety features make it suitable for broader applications.