About thirty years ago, researchers found two strange chemicals in rye pollen that slowed tumor growth in animals. The work stopped because they could not see the exact 3‑D shape of the chemicals.
Now a team at Northwestern University has solved that puzzle. By building the chemicals step‑by‑step in the lab, they proved the true structures of secalosides A and B for the first time.
With a clear molecular map, scientists can study how these rye pollen compounds talk to the immune system. That knowledge might help create new, safer ways to fight cancer.
The results were published in the Journal of the American Chemical Society.
"Earlier studies showed rye pollen could shrink tumors in animals without harming them," said Karl A. Scheidt, the study leader. "Now we know the exact shape, we can find the active part and improve it for future cancer medicines."
Scheidt is a chemistry professor at Northwestern’s Weinberg College and also works with the university’s cancer center.
Nature as a Medicine SourceMany medicines start from nature. The pain drug morphine comes from poppy plants, the chemotherapy drug Taxol was first taken from the yew tree, and cholesterol‑lowering statins were discovered in fungi.
"Natural products are great clues, even if they are not perfect drugs themselves," Scheidt explained. "We can redesign them to work better in the body."
Rye pollen may join this list. It is already sold as a supplement for prostate health, but it has not become a prescription drug because its exact molecular picture was missing.
Untangling a Decades‑Long MysteryTraditional tools like advanced NMR could not decide which of two mirror‑image shapes the molecules had. Both versions used the same atoms, but one was a left‑hand version and the other a right‑hand version. Small differences like this can change how a molecule works in the body.
"It’s like having a left‑hand glove and a right‑hand glove," Scheidt said. "You need the right glove for the right hand."
Building the Molecules From ScratchTo end the debate, the Northwestern team used total synthesis – a lab method that assembles a natural molecule piece by piece.
The task was tough because secalosides A and B contain a very rare, tightly squeezed ten‑membered ring. The scientists first made a larger, flexible ring, then triggered a reaction that snapped it into the tiny, strained ring in one step.
After creating both possible versions, they compared them with material taken from real rye pollen. Only one matched perfectly, confirming the correct structure.
"Now we can make the core of this natural product," Scheidt noted. "We are looking for immunology partners to see if it can move toward clinical use."
The study, titled "Synthesis and structural confirmation of secalosides A and B," received funding from the National Institute of General Medical Sciences, the Chemistry of Life Processes Institute, and the National Science Foundation.