Purification of Artemisinin from the Product Solution of a Semisynthetic Reaction within a Single Crystallization Step

Artemisinin, a natural compound isolated from the Artemisia annua L. plant, represents an indispensable ingredient in artemsisinin-based combination therapies (ACT) against malaria. Starting from dihydroartemisinic acid, a biosynthetic precursor of the target, a semisynthetic pathway described previously provides in the reactor effluent approximately 69% artemisinin together with structurally similar byproducts. Successful purification of artemisinin was achieved by a combination of continuous chromatography and crystallization. This work is directed to isolate crystalline artemisinin of high purity from the effluent of the catalytic reaction by crystallization only. On the basis of knowledge of artemisinin solubility and nucleation behavior in the reaction medium, a seeded cooling crystallization was designed and implemented subsequent to organic synthesis. It provided crystalline artemisinin with a final purity of 99.9% in a single straightforward crystallization step, simplifying the overall purification process significantly. The new purification method was further demonstrated to successfully isolate pure crystalline artemisinin from a synthesis solution produced directly using crude A. annua extract as initial feed.