CHAMPAIGN, Ill. (WCIA) — An Illinois research team has recently discovered a way to produce a special class of molecule that could open the door for new drugs to treat untreatable diseases.

Organic derivatives of ammonia, called amines, are one of the most prevalent structures found in medicine today. According to officials, more than 40 percent of drugs and drug candidates contain amines, and 60 percent of those amines are tertiary, so named for the three carbons that are bonded to a nitrogen.

Officials stated, “Tertiary amines are found in some of the most impactful human medicines, including antibiotics, breast cancer and leukemia drugs, opioid pain medications, antihistamines, blood thinners, HIV treatments, antimigraine medications and more. They increase a drug’s solubility and can trigger its key biological functions.”

Much of the functional potential of tertiary amines has remained untapped. It is because the traditional process of making them requires specific, controlled conditions that inherently limit the discovery of new tertiary amines, which could potentially treat a wide range of currently untreatable diseases.

An Illinois research team led by Lycan Professor of Chemistry M. Christina White and graduate students Siraj Ali, Brenna Budaitis and Devon Fontaine have discovered a new chemical reaction, a carbon-hydrogen amination cross-coupling reaction, that creates a faster, simpler way of making tertiary amines without the limitations of classic methods.

This new reaction in the chemist’s toolbox transforms the traditional tertiary amine building process into a procedure that can be carried out in general conditions open to air and moisture with the potential for automation. The researchers said this new procedure uses a metal catalyst discovered by their group (Ma-WhiteSOX/palladium) and two building blocks— abundant hydrocarbons (olefins containing adjacent C—H bond) and secondary amines— to generate a variety of tertiary amines.

According to Dr. White, the discovery has the potential for chemists to take a lot of different secondary amines and couple them with a lot of different olefins, both of which you can either buy or easily make.

“These are stable starting materials. You could have them in individual containers, mix and match them, and using our catalyst make many different combinations of tertiary amines,” said Dr. White. “The flexibility of this reaction makes the discovery process for tertiary amine drugs easier.”

This highly flexible system for making tertiary amines is also very practical.

“You could, in principle, run it on your stovetop,” White explains. “You don’t need to handle it with a lot of precautions, you can run it open to the air and you don’t have to exclude water. You just need your starting materials, the palladium/SOX catalyst and a little heat. It should work just the way we are doing it in the lab.”

Dr. White said when a pharmaceutical company wants to make tertiary amines, they often have to use specialized procedures, but this reaction allows them to take two simple, often commercial, starting materials and put them together using the same procedure.

“Because the conditions are so simple and work for so many different amines and olefins there is great potential to adopt this reaction for automation,” she added.

The major challenge the team overcame in this discovery was solving a long-standing problem in C—H functionalization chemistry: replacing a hydrogen atom on a molecule’s carbon framework with a basic, secondary amine to directly make tertiary amines.

The researchers made 81 tertiary amines in their study, coupling a wide range of complex, medicinally relevant secondary amines to many complex olefins containing reactive functionality. This includes functionality that is reactive with secondary amines in the traditional tertiary amine manufacturing processes.

Click here to watch a video explaining the study.