The aim of this work is to study sustainable approaches to pure betulin using green low-polar solvents from natural feedstockpine monoterpenes and limonene. The conventional methods of extracting outer birch bark (OBB) lead to extracts that contain only 50%−75% of betulin, while refining processes of OBB extracts are usually labor consuming and employ toxic solvents. The extractions of OBB using monoterpenes and their hydrogenated analogs at boiling and microwaveassisted conditions turned out to be insufficiently selective and lead to a significant uptake of extractants on the depleted bark. To obtain pure betulin, the sequence including energy-saving extraction of OBB with a green solvent (ethyl acetate, EtOAc), saponification of the extract, and purification of betulin in limonene or hydrogenated monoterpenes was proposed. The protocol of processing primary extracts with stable monoterpeneslimonene, pinane, and hydrogenated turpentine oil ensured separation of pure betulin (95%−97%) with high yields (75%−82%) and the effective recycling of extractants (81%− 87%). The refining of plant metabolites in monoterpenes can be regarded as a promising method, successfully competing with the known multistep processes and methods employing toxic solvents.
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