Mirror Molecules: Key to Innovative Drug Discovery

A chemist from the University of Texas at Dallas and his research team have created an innovative chemical reaction that enables the selective synthesis of left-handed or right-handed versions of mirror molecules. These molecules show promise for treating various health issues, including cancer, infection, depression, and inflammation.

This advancement is significant because the left- and right-handed forms of chemical compounds (known as enantiomers) interact differently within the human body, despite sharing identical chemical properties. Developing efficient methods to produce only the desired enantiomer is essential for progress in medicinal chemistry.

In a study featured in Science, the researchers outline a technique that swiftly and effectively yields a pure sample of a single enantiomer. This process involves incorporating prenyl groups into enones through a newly designed catalyst in a single step.

Dr. Filippo Romiti, one of the study’s lead authors, pointed out that replicating nature’s method of assembling these molecules has historically been difficult. He believes this research signifies a major step forward in producing large quantities of biologically active molecules for therapeutic exploration.

Natural compounds play a crucial role in discovering new medications, but they are often found in small quantities. The researchers demonstrated that their new reaction can be completed in around 15 minutes at room temperature, making it far more energy-efficient than traditional techniques that require significant temperature adjustments.

Romiti collaborated with scientists from Boston College, the University of Pittsburgh, and the University of Strasbourg to bring this reaction to fruition. Their efforts focused on synthesizing polycyclic polyprenylated acylphloroglucinols (PPAPs), a class that encompasses over 400 natural products with a wide range of biological activities.

In their proof of concept, the team successfully synthesized enantiomers of eight PPAPs, including nemorosonol, known for its antibiotic effects. They tested the nemorosonol enantiomer on lung and breast cancer cell lines, observing promising results. Romiti emphasized that this breakthrough was possible only because they had access to large amounts of pure enantiomers, opening doors for further research and advancements in drug discovery and translational medicine.