Rye pollen molecule structures confirmed after decades-long puzzle

Chemists at Northwestern University have confirmed the 3D structures of two molecules found in rye pollen, resolving a problem that had limited follow-up research for nearly three decades. The finding gives scientists a molecular map for studying compounds that earlier animal studies linked to tumor-fighting effects, though Northwestern said no drug has been developed from them.

The molecules, known as secalosides A and B, were built in the lab and compared with material extracted from rye pollen, according to Northwestern University. The work was published in the Journal of the American Chemical Society under the title “Synthesis and Structural Confirmation of Secalosides A and B.”

A stalled lead from nature

Northwestern said researchers first identified the unusual rye pollen molecules about 30 years ago after animal studies suggested they could slow tumor growth or help clear tumors. The lead stalled because scientists could not determine the molecules’ exact 3D arrangement, a key requirement for understanding how a compound might act in the body.

Karl A. Scheidt, the Northwestern chemist who led the study, said earlier researchers saw effects in animal models through an unknown mechanism that did not appear toxic. “Now that we confirmed the structure of these molecules, we can find the active ingredient — or what part of the molecule is doing the work,” Scheidt said in Northwestern’s announcement.

Scheidt is a professor of chemistry at Northwestern’s Weinberg College of Arts and Sciences and a professor of pharmacology by courtesy at the Feinberg School of Medicine, according to the university. Northwestern said he is also affiliated with the Chemistry of Life Processes Institute and the Robert H. Lurie Comprehensive Cancer Center.

Why structure mattered

According to Northwestern, standard methods, including advanced nuclear magnetic resonance spectroscopy, could not fully settle how one important region of the molecules was arranged. Scientists had been weighing two possible structures that contained the same atoms and connections but differed in a mirror-image feature.

That distinction can affect whether a molecule fits a biological target, Northwestern said. Scheidt compared the problem to hands and gloves: mirror images can look closely related, but the wrong orientation can fail to work.

To settle the question, the Northwestern team used total synthesis, a chemistry approach that builds a natural product step by step in the laboratory. The university said the task was difficult because secalosides A and B contain a rare, strained 10-membered ring at their center.

The researchers first made a larger and more flexible ring, then used a chemical reaction to convert it into the smaller strained ring in one step, according to Northwestern. After making both proposed versions, the team compared them with rye pollen samples and found that only one matched.

Next questions

Northwestern said the confirmed structures should allow researchers to test how the compounds interact with the immune system and which parts of the molecules may be responsible for biological activity. Scheidt said the team is seeking immunology collaborators to help move the work toward a possible clinical endpoint.

The university placed the work in a broader history of natural products guiding drug discovery, citing morphine from the opium poppy, Taxol from the Pacific yew tree and statins from fungi. Scheidt said natural compounds are often starting points rather than ready-made medicines, because chemists may need to alter them to improve stability, delivery or targeting.

Northwestern said rye pollen extract is already sold as a dietary supplement used by many people for prostate health, but it has not become a pharmaceutical treatment. The study was supported by the National Institute of General Medical Science, the Chemistry of Life Processes Institute Lambert Fellowship and the National Science Foundation, according to the university.

This story draws on original reporting from ScienceDaily.