Electrochemically Induced Sequential Phosphorylation/Cyclization Access to Phosphorylated Pyridophenanthridines

Area of Science:

• Organic Chemistry
• Electrochemistry
• Medicinal Chemistry

Background:

• Pyrido-[4,3,2-gh]-phenanthridine derivatives are important heterocyclic compounds.
• Efficient synthesis of complex organic molecules is crucial for drug discovery.
• Electrochemical methods offer sustainable and controlled reaction pathways.

Purpose of the Study:

• To develop a novel electrochemical synthesis for phosphorylated pyrido-[4,3,2-gh]-phenanthridine derivatives.
• To investigate a cascade phosphorylation/cyclization reaction mechanism.
• To evaluate the preliminary anticancer activity of the synthesized compounds.

Main Methods:

• Utilized a Cp2Fe-assisted electrochemical cycle for synthesis.
• Employed a cascade reaction involving phosphonyl radical addition and cyanide insertion.
• Performed preliminary in vitro screening against cancer cell lines.

Main Results:

• Achieved synthesis of phosphorylated pyrido-[4,3,2-gh]-phenanthridine derivatives with yields up to 91%.
• Demonstrated mild reaction conditions and broad functional group tolerance.
• Identified compounds with promising inhibitory effects on selected cancer cell lines.

Conclusions:

• A novel and efficient electrochemical method for synthesizing phosphorylated pyrido-[4,3,2-gh]-phenanthridine derivatives has been established.
• The developed method is mild, tolerant of various functional groups, and high-yielding.
• The synthesized compounds exhibit potential as anticancer agents, warranting further investigation.