Multiatom Skeletal Editing to Access SeCN-Containing Bicyclo[1.1.1]pentanes with Antitumor Activity

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Drug Discovery

Background:

• Multiatom skeletal editing is crucial for synthesizing complex molecules with multiple pharmacophores.
• Developing efficient and green synthetic strategies is essential for modern drug discovery.

Purpose of the Study:

• To report the first synthesis of SeCN-substituted bicyclo[1.1.1]pentanes using multiatom skeletal editing.
• To evaluate the antitumor activity of the synthesized compounds.
• To establish an innovative synthetic platform for generating new molecular entities.

Main Methods:

• Combined multiatom skeletal editing with pharmacophore combination.
• Utilized the green solvent 2-methyltetrahydrofuran.
• Performed late-stage modification of amino acids, natural products, and drugs.

Main Results:

• Successfully synthesized SeCN-substituted bicyclo[1.1.1]pentanes.
• Identified a hit compound (3v) with an unprecedented scaffold and superior antitumor activity compared to the positive control.
• Demonstrated high atom economy and avoided the need for photocatalysts, oxidants, or transition metals.

Conclusions:

• The developed method offers a green and efficient approach for synthesizing novel SeCN-substituted bicyclo[1.1.1]pentanes.
• The identified hit compound shows significant potential for further development as an anticancer therapeutic.
• This work provides a new research paradigm for drug discovery through innovative synthetic platform development.