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The natural product artemisinin and its derivatives are the most effective treatments in the fight against malaria. A new general hydrogenation procedure by C. Oliver Kappe and coworkers of the University of Graz, in Austria, could help eliminate a bottleneck in the synthesis of the drugs (Chem. Eur. J. 2015, DOI: 10.1002/chem.201406439). Artemisinin is currently made two ways: by a semisynthetic route starting from the intermediate artemisinic acid produced by engineered yeast, and by a continuous-flow process starting with the intermediate dihydroartemisinic acid. An efficient large-scale method for reducing artemisinic acid to dihydroartemisinic acid has been a missing link. Kappe’s team developed a catalyst-free flow reactor method to generate diimide (N2H2) in situ from inexpensive hydrazine hydrate (N2H4•H2O) and O2 and use it as a reagent for the hydrogenation of artemisinic acid. The procedure avoids the need for H2 and a precious-metal catalyst—typically used in hydrogenations—and leaves N2 as the only by-product.
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