DOI: 10.1126/sciadv.aej0213 ISSN: 2375-2548

Crystalline three-dimensional membranes enable chromatography-free purification of natural products

Xiao-Fan Hu, Han-Qing Yu, Menachem Elimelech, Yan-Fang Guan

Chromatographic purification of natural products is solvent intensive and energy-demanding and remains a major bottleneck in the sustainable production of pharmaceutical compounds. Here, we show that crystalline three-dimensional membranes enable chromatography-free purification of complex natural product mixtures by organic solvent nanofiltration. The rigid, nanomechanically robust channels of the membrane sustain continuous 6-day operation with commercial Taxus crude extracts, achieving ∼96% retention and fourfold enrichment of paclitaxel while allowing valuable precursors to permeate. The membranes exhibit high solvent permeance with negligible swelling, enabling stable molecular sieving in methanol across extended operation. Scalable fabrication via nanosphere-assembled interfacial polymerization produces continuous crystalline membranes over large areas. Life cycle assessment reveals nearly an order-of-magnitude reduction in carbon emissions compared with liquid chromatography. These results demonstrate a membrane platform that can replace chromatographic steps in natural product drug purification, offering a sustainable route for active pharmaceutical ingredient production.

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