# Rapid Structural Analysis of Natural Products Using MicroED

**Authors:** Jieye Lin, Orel Paz, Johan Unge, Tamir Gonen

PMC · DOI: 10.1002/smll.202511875 · Small (Weinheim an Der Bergstrasse, Germany) · 2026-01-23

## TL;DR

MicroED is shown to be a fast and efficient method for determining the structures of complex natural products that were previously difficult to analyze.

## Contribution

The paper demonstrates that MicroED can be systematically applied to natural product structure elucidation using microgram quantities of material.

## Key findings

- MicroED successfully solved the 3D structures of nine chemically diverse natural products that had resisted structural analysis for years.
- The method achieves a success rate comparable to other techniques while using significantly smaller sample amounts.
- MicroED bypasses the need for large single crystals, making it a general and efficient tool for natural product analysis.

## Abstract

Structural analysis of natural products remains challenging due to their inherent complexity and limited availability. By solving nine chemically diverse natural products of high priority that have resisted reported 3D structures for years, we demonstrate that microcrystal electron diffraction (MicroED) can systematically and feasibly be applied to natural‐product structure elucidation on samples that were previously unattainable by other structural methods. In addition, using microgram quantities of material and side‐stepping the process to create large single crystals, the success rate is still comparable to other techniques on a general sample using larger amounts of the sample. We suggest that MicroED is not only a necessary technique but also a general and efficient tool for many applications.

The cryoEM method, MicroED used for rapid analysis and structure determination of natural products that remained unattainable by other structural biology methods

## Full-text entities

- **Diseases:** toxicity (MESH:D064420), Alzheimer's disease (MESH:D000544), inflammatory (MESH:D007249)
- **Chemicals:** chalconoid (MESH:D047188), lactone (MESH:D007783), progesterone (MESH:D011374), L-rhamnose (MESH:D012210), quinazolinone (MESH:D052999), Licochalcone A (MESH:C070840), icariside I (MESH:C526898), eurycomanone (MESH:C506425), fraxin (MESH:C080614), glycan (MESH:D011134), chalcone (MESH:D002599), H (MESH:D006859), furan (MESH:C039281), Baohuoside I (MESH:C060988), 3-hydroxypiperidine (-), Azadiradione (MESH:C479321), lomaiviticin A (MESH:C433842), lycodine (MESH:C585001), Isofebrifugine (MESH:C001207), C (MESH:D002244), azadirone (MESH:C487479), coumarin (MESH:C030123), yadanziolide S (MESH:C467917), flavonoid (MESH:D005419), alkaloid (MESH:D000470), amine (MESH:D000588), Water (MESH:D014867), Huperzine B (MESH:C053016), romidepsin (MESH:C087123), butanol (MESH:D000440), limonoid (MESH:D036701), ailanthone (MESH:C029825), fraxidin (MESH:C401933), 7-hydroxy-6,8-dimethoxycoumarin (MESH:C008182), copper (MESH:D003300), quassinoid (MESH:D036702), icariin (MESH:C056599), Licochalcone B (MESH:C541528), hydroxyl (MESH:D017665), Fraxetin (MESH:C105671), icaritin (MESH:C499403), fischerin (MESH:C083903), OH (MESH:C031356), alkane (MESH:D000473)
- **Species:** Azadirachta indica (Indian-lilac, species) [taxon 124943], Huperzia serrata (toothed club-moss, species) [taxon 355589], Epimedium davidii (species) [taxon 253605], Fraxinus excelsior (European ash, species) [taxon 38873], Eurycoma longifolia (species) [taxon 458531], Hydrangea febrifuga (species) [taxon 152286], Glycyrrhiza glabra (species) [taxon 49827]
- **Mutations:** C25 H, C23 H, C H, C10 H, C17 H

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12980483/full.md

## References

71 references — full list in the complete paper: https://tomesphere.com/paper/PMC12980483/full.md

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Source: https://tomesphere.com/paper/PMC12980483