Northwestern Solves 30-Year Rye Pollen Molecule Mystery
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- Karl A. Scheidt and Northwestern chemists confirmed the precise 3D structures of secalosides A and B for the first time by building the molecules from scratch in the lab, ending a 30-year-old deadlock that had stalled cancer-related research on these rye pollen compounds.
- The synthesis proved exceptionally difficult because the molecules contain a rare, highly strained 10-membered ring; the team worked around it by first assembling a larger, more flexible ring, then converting it into the strained ring in a single chemical step.
- Traditional NMR spectroscopy could not distinguish between two competing structural models that differed only in a mirror-image region — a subtlety comparable to left- vs. right-handed gloves, Scheidt said — so synthesis was the only way to settle the debate.
- The team synthesized both candidate structures and compared them against natural rye pollen extracts; only one matched perfectly, definitively identifying the correct configuration of each molecule.
- The findings were published in the Journal of the American Chemical Society (DOI: 10.1021/jacs.5c18864), with support from the National Institute of General Medical Science, an NSF grant, and the Chemistry of Life Processes Institute Lambert Fellowship.
- With the structure now confirmed, Scheidt said researchers can hunt for the specific active portion of the molecule and explore whether engineered versions could inform new cancer therapies; rye pollen extract is already sold as a dietary supplement for prostate health but has never been developed into a pharmaceutical.
Why it matters: For three decades, promising animal data on tumor clearance by rye pollen molecules sat in limbo because no one could determine exactly what they looked like — and without a confirmed structure, no drug-chemistry program could begin. Scheidt's team has now handed cancer researchers the molecular blueprint they needed to identify the active component and design improved versions, the precondition for any pharmaceutical development of these compounds.
