A team of chemists at the University of Texas at Dallas have developed a new chemical reaction that enables the selective synthesis of mirror molecules or enantiomers found in nature. These mirror molecules have identical chemical properties but can have different biological effects in the human body. Being able to synthesize only the desired version of these molecules is crucial for medicinal chemistry. Published in Science, the study describes a method to efficiently produce samples that are purely one enantiomer of a mirror-image pair of molecules, rather than a mixture of the two.
Dr. Filippo Romiti, an assistant professor at UT Dallas and corresponding author of the study, explained that their new chemical synthesis method involves adding prenyl groups to enones using a newly developed catalyst. This approach mimics the way nature creates these molecules and has been challenging for scientists to replicate successfully. By utilizing this method, researchers can now synthesize large quantities of biologically active molecules and test them for therapeutic activity. The speed and efficiency of the new chemical reaction allow for a more cost-effective and scalable production process compared to traditional methods.
Naturally occurring compounds are potential sources of new medicines, but their limited availability in nature requires scientists to develop methods to synthesize larger quantities for testing or drug manufacturing. In the study, researchers demonstrated how incorporating their new chemical reaction into the synthesis process could be completed in about 15 minutes at room temperature. This energy-efficient approach eliminates the need to heat or cool substances significantly during the reaction, making it more sustainable and practical for large-scale production.
Collaborating with researchers from various institutions, Dr. Romiti’s team focused on synthesizing a class of natural products called polycyclic polyprenylated acylphloroglucinols (PPAPs), which have diverse biological activities including anticancer, anti-HIV, and anti-inflammatory properties. By synthesizing enantiomers of eight PPAPs, including nemorosonol, a compound with antimicrobial activity, the researchers demonstrated the proof of concept for their method. Testing the nemorosonol enantiomer against lung and breast cancer cell lines showed promising effects, highlighting the potential impact of their research on cancer treatment and drug discovery.
The new chemical reaction developed by the team has implications for drug discovery and translational medicine. Beyond enabling more efficient drug manufacturing processes, the method allows for the creation of optimized versions of natural products called analogs that can be more potent or selective in their biological activity. This advancement provides chemists and biologists with a valuable tool to study and test the biological activity of numerous natural product derivatives that were previously challenging to synthesize in the laboratory.
Future research will focus on applying the new reaction to the synthesis of other classes of natural products, expanding the potential applications of the method. Dr. Romiti’s work in this area has been supported by grants from organizations like the National Institutes of Health, further emphasizing the significance of this research in advancing medicinal chemistry and drug development. Overall, the study represents a significant advancement in chemical synthesis techniques that have the potential to revolutionize the field of natural product-based drug discovery.