Breakthrough Synthesis Method Unlocks Potential of Mirror Molecules for Drug Discovery
A new synthesis method to come out of the University of Texas at Dallas should soon make the rapid and scalable creation of pure mirror molecules possible, unlocking all the potential of advanced drug discovery.
University of Texas at Dallas scientists have invented a new chemical synthesis method that for the first time will allow large quantities of so-called “mirror molecules” of compounds found in nature to be produced-the left- or right-handed versions of chemicals, opening doors to realizing potentially game-changing opportunities for drug developers. It promises to enable the manufacture of significant quantities of pure enantiomers, which can lead to treatments for everything from cancer and infections to depression and many other afflictions. It is an innovative method that is going to make the synthesis process relatively faster because energy losses incorporated with maintaining energy efficiency would end; this is sure to transform the sphere of medicinal chemistry and therapeutic research.
How a New Chemical Reaction is Facilitating Simpler and Quicker Synthesis of Pure Enantiomers
The left- and right-handed forms, or enantiomers, of molecules have precisely the same chemical properties but often have very different biological activity. For instance, one may have therapeutic activity while the other is inactive or even toxic. Clearly in order to design safe, effective drugs, methods of selectively producing single enantiomers are also required. This new synthesis method developed by Dr. Filippo Romiti et al meets this need by facilitating rapid, scalable, and efficient production of pure enantiomers with the system easily producible within just 15 minutes at room temperature.
Secret to Speed and Scalability: Adding Prenyl Groups
This novel strategy is founded on the fact that prenyl groups, composed of five carbon atoms, are added to enones-a class of organic compound-through a specially designed catalyst. The biogenic prenyl process provides access to the synthesis of most biologically active molecules; however, this process has been very difficult for scientists to achieve in a laboratory. The Romiti team succeeded in solving the mystery and perfecting the synthesis step to completion with low energy input and at high speed, along with the generation of an optically pure enantiomer.
Their approach is highly relevant for the synthesis of the polycyclic polyprenylated acylphloroglucinols, a group of more than 400 natural products exhibiting broad bioactivity in cancer, HIV, Alzheimer’s, epilepsy, and obesity conditions. There is an urgent need for medicinal chemists to prepare these natural products in larger amounts and further investigate them for therapeutic applications.
Proof of Concept: Investigating the Effects of the Technique
The researchers had synthesized eight enantiomers of PPAPs, including nemorosonol, a compound from a Brazilian tree known to have antimicrobial activity. Only by isolating pure enantiomers could the team begin for the first time ever to determine which version of the molecule was doing what in producing its biological effects. Results for the first lung and breast cancer cell line screens were encouraging, in that one enantiomer of the nemorosonol showed a great deal of anticancer activity. This discovery showed promise for accessing pure enantiomers as pathways for the better understanding and utilization of therapeutic potential from such natural products.
Accelerating Drug Discovery with Scalable Synthesis Techniques of Mirror Molecules
The novel synthesis route breaks new avenues open for drug discovery and translational medicine. In bulk and pure, the enantiomers can quickly be produced in good quantities. This can allow researchers to optimize analogues of the natural products that are more potent or more selective for specific biological activities. This could revolutionize the speed of accelerating new drug development since candidates may easily be screened quickly.
Romiti and colleagues want to apply this class of method to other types of natural products, which may yield yet more drug leads. The collaboration will be supported for five years by a $1.95 million grant from the National Institute of General Medical Sciences, continuing their exploration of synthesizing the complex molecules that might one day save lives.
Revolutionizing Synthesis of Natural Product Pharmaceuticals
There is no better example of great medicinal chemical advancements than a synthesis protocol based on flow chemistry. It ensures a very efficient access to pure enantiomers with more scalability. Hence, this is not only streamlining drug discovery, but it’s also opening the horizon to develop natural-product-based therapies. With further development and adaptation of this technology to other bioactive compounds, I believe it will revolutionize the way we produce new medicines and test them. The rapid generation of potential candidates for large numbers certainly means that the laboratory bench-to-medical application route will be accelerated. This will bring hope to millions of patients suffering worldwide.
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