Advanced crystallography for structure determination of natural products

Covering: up to 2025Crystallographic analysis has become the most reliable method for elucidating the structures of natural products, as it can provide absolute configurations with precise spatial arrangement information at the molecular level. However, obtaining high-quality and suitable-sized single crystals can be challenging for many natural products, making their structure determination difficult through traditional crystallography techniques. Recent advancements in this field have introduced innovative strategies to overcome the obstacle. These cutting-edge strategies include post-orientation of organic molecules within pre-prepared porous crystals (crystalline sponge method), co-crystallization of organic molecules with a crystalline mate through supramolecular interactions (crystalline mate method), encapsulation of organic molecules within inert oil nanodroplets (encapsulated nanodroplet crystallization method), and the use of electron diffraction and microscopy for nanocrystals (microcrystal electron diffraction method). This highlight delves into the fundamental principles, key characteristics, and representative applications of each strategy, as well as their respective advantages and limitations, aiming to guide researchers in choosing the most suitable crystallography approach for analyzing the structures of natural products.