At a Glance
- University of Delaware chemists have successfully synthesized the anti-cancer natural product (–)-psiguadial A in the lab for the first time using readily available chemicals.
- This complex molecule, initially found in guava plants, shows significant promise in fighting aggressive and difficult-to-treat liver cancers, a growing global health concern.
- The new synthetic pathway provides a low-cost and scalable “recipe,” overcoming the natural scarcity of the compound and enabling much broader scientific research and development.
- A key step in the process involved a novel chemical reaction to form a highly congested carbon bond, followed by a clever ring closure to build the molecule’s unique core.
- The research team is now collaborating with the National Cancer Institute to explore the molecule’s effectiveness against liver cancer and its potential application for other cancer types.
Researchers at the University of Delaware have successfully recreated a potent anti-cancer molecule originally found in guava plants, thereby providing a new pathway for developing treatments for aggressive liver cancers. The work, led by Associate Professor William Chain, utilizes a process called natural product total synthesis to construct the complex compound, known as (–)-psiguadial A, from simple, widely available laboratory chemicals. This breakthrough offers a solution to the natural scarcity of the molecule, which has limited its study and potential therapeutic use. The team’s complete method was published in the international chemistry journal Angewandte Chemie.
Natural product total synthesis is a field of chemistry focused on creating a “recipe” to build complex molecules found in nature entirely from scratch. For (–)-psiguadial A, the challenge was significant due to its intricate, three-dimensional structure. The Delaware team’s innovative approach involved first building a complex terpenoid component—a class of organic compounds often found in plant oils. They then joined this piece to another chemical fragment using a novel coupling reaction to form a difficult, congested connection between atoms, before executing a final, carefully controlled reaction to form the molecule’s unique seven-membered ring core.
The importance of this achievement lies in its potential to accelerate cancer research and drug development. “The majority of clinically approved medicines are either made from a natural product or are based on one,” Chain said in a university press release. “But there aren’t enough natural resources to make enough treatments.” By providing a scalable, low-cost method to produce (–)-psiguadial A, this research empowers scientists worldwide to investigate its full potential. “Now chemists will be able to take our manuscripts and basically follow our ‘recipe’ and they can make it themselves,” he added.
With liver and bile duct cancers on the rise globally and five-year survival rates for late-stage diagnoses below 15%, new therapeutic options are urgently needed. The University of Delaware team is already collaborating with the National Cancer Institute to advance the research, exploring how effectively the synthesized molecule can combat liver cancer cells and whether its properties could be helpful against other forms of the disease. This work paves the way for creating new, more effective, and accessible medicines rooted in the chemical power of nature.
References
- Douwes, H. & University of Delaware. (2025, August 19). Synthesis of a molecule found in guava plants offers hope in fighting liver-related cancers. Phys.Org; University of Delaware. https://phys.org/news/2025-08-synthesis-molecule-guava-liver-cancers.html
- O’Grady, L. P., Achtenhagen, M., Wisthoff, M. F., Lewis, R. S., Pfeifer, K., Zheng, W., Martin, M. I., Yap, G. P. A., & Chain, W. J. (2025). Enantioselective total synthesis of (–)‐psiguadial a. Angewandte Chemie, 137(30), e202506537. https://doi.org/10.1002/ange.202506537
