UNIST Develops Pharmaceutical Ingredient Synthesis Method Using Electrolysis

Professor Park Cheol-min's Team Develops Nitrogen Heterocycle Synthesis Method... Green Light for New Drug Development
Producing Pharmaceutical Components Cleaner and at Lower Cost

Professor Park Cheolmin at UNIST.

[Asia Economy Yeongnam Reporting Headquarters Reporter Kim Yong-woo] A technology that easily synthesizes pharmaceutical ingredients using electrical energy has been developed, attracting attention. It is an important research result in the field of new drug development.

The research team led by Professor Park Cheol-min of the Department of Natural Sciences at Ulsan National Institute of Science and Technology (UNIST) developed a synthesis method to produce 'indolopyran,' a type of 'nitrogen heterocyclic compound,' using electrical energy.

This is an eco-friendly and economical synthesis method that induces reactions using abundant 'oxygen' in the air, without elements that cause pollution such as metal catalysts or high temperatures. The same synthesis method can also produce 'oxygen heterocyclic compounds,' which is expected to greatly aid new drug development research.

Nitrogen heterocyclic compounds are included in about 60% of drugs recently approved by the FDA. They have a structure where nitrogen atoms are inserted between carbon atoms bonded in a ring form, and drugs are synthesized by attaching functional groups here.

The difficulty of synthesis varies depending on the shape of the ring and the type of functional groups. Indolopyran, recently noted for its anticancer effects, is one of the difficult substances to synthesize. There are not many synthesis methods, and those that exist require reagents (bases) and metal catalysts or can only be synthesized at high temperatures.

Professor Park Cheol-min's team synthesized indolopyran by pairing two substances, 'indole' and 'active methylene,' through reactions occurring at the cathode and anode of the electrode.

Schematic diagram of the synthesis process of indolopyran using electrical energy and the concept of bioactive compounds containing indolopyran.

At room temperature, oxygen in the air was used as a reagent, and iodide was used as a catalyst instead of metal. A separate reagent (base) with 'deprotonation ability' is required for the reaction to occur, but this synthesis method has the advantage of being able to use oxygen in the air as a pre-base. Additionally, by using a constant voltage mode that maintains a steady voltage, the problem of functional group damage caused by high voltage was overcome.

Subin Choi, a combined master's and doctoral course researcher in the Department of Natural Sciences who led the study, explained, "Unlike synthesis methods that mainly use only one electrode, we were able to synthesize indolopyran with a complex structure by utilizing reactions occurring at both the anode and cathode."

The research team found the generation principle of indolopyran through Density Functional Theory and various designed reaction pathway identification experiments.

At the cathode and anode, iodine and oxygen undergo redox reactions to produce iodine radicals and superoxide radicals, respectively, and the superoxide radical acts as a base to proceed with the reaction.

After the 'coupling' reaction of indole and active methylene compounds, the intermediate substance is finally completed as indolopyran through an 'electrocyclization reaction' that forms the ring shape.

Professor Park Cheol-min said, "Unlike existing synthesis methods, we were able to synthesize nitrogen heterocyclic compounds by applying an eco-friendly and economical organic synthesis method using electrical energy."

This research was selected as a Hot Paper in the top chemistry journal 'Angewandte Chemie International Edition' and was published on July 7. The research was conducted with support from the National Research Foundation of Korea.

This content was produced with the assistance of AI translation services.