Artemisinin, a secondary metabolite of sweet wormwood, is the basis for the production of the most effective antimalarial drugs. Since the amount of artemisinin currently produced from plants is not sufficient to treat the worldwide malaria cases, an effective semisynthetic method was developed recently that is capable of producing artemisinin from dihydroartemisinic acid (DHAA). DHAA is a byproduct obtained during the extraction of artemisinin from plant leaves. The photocatalytic reaction to convert DHAA to artemisinin can be performed continuously in a tubular reactor using toluene as a solvent. The reactor effluent contains besides artemisinin the photocatalyst (dicyanoanthracene) and several compounds that are structurally similar to artemisinin, including unreacted DHAA starting material. To isolate artemisinin from the reaction mixture, two separation techniques were applied, crystallization and chromatography. The solid obtained by seeded cooling crystallization was highly enriched in artemisinin but contained also traces of the photocatalyst. In contrast, using a variant of continuously operated multicolumn simulated moving bed (SMB) chromatography, which splits the feed into three fractions, we were able to recover efficiently the photocatalyst in the raffinate stream. The extract stream provided already almost pure artemisinin, which could be finally further purified in a simple crystallization step

Bis(demethoxy)curcumin (BDMC), extracted from rhizomes of the traditional herb Curcuma longa, has revealed a wide range of medicinal applications, such as antimicrobial and anticarcinogenic. Pure BDMC was obtained by recrystallization from ethanol and three BDMC solvates were identified with acetone, methanol and isopropanol. The crystal structures of pure BDMC and the solvates were resolved by single crystal X-ray diffraction. Analyses of the crystal structures and calculations of crystal packing efficiencies revealed that pure BDMC is efficiently packed. The solvents involved are not utilized to fill the void spaces in the crystal structures, but to provide effective intermolecular interactions. The stoichiometry of the three solvates obtained from single crystal data is 1:1, which is in good agreement with the gravimetric analyses. Furthermore, the desolvation process and stability of the solvates were investigated by various analytical techniques including X-ray diffraction, differential scanning calorimetry, thermogravimetric analyses, hot-stage microscopy and dynamic vapor sorption. Results show that the methanol solvate is more stable compared to the acetone and isopropanol solvates attributed to the strong hydrogen bonding network. Moreover, the desolvation process of the three solvates proceeds through a destructive-reconstructive mechanism.

Crystallization-based separation of curcumin from ternary mixtures of curcuminoids having compositions comparable to commercial extracts was studied experimentally. Based on solubility and supersolubility data of both, pure curcumin and curcumin in presence of the two major impurities demethoxycurcumin (DMC) and bis(demethoxy)curcumin (BDMC), seeded cooling crystallization procedures were derived using acetone, acetonitrile and 50/50 (wt/wt) mixtures of acetone/2-propanol and acetone/acetonitrile as solvents. Starting from initial curcumin contents of 67–75% in the curcuminoid mixtures single step crystallization processes provided crystalline curcumin free of BDMC at residual DMC contents of 0.6–9.9%. Curcumin at highest purity of 99.4% was obtained from a 50/50 (wt/wt) acetone/2-propanol solution in a single crystallization step. It is demonstrated that the total product yield can be significantly enhanced via addition of water, 2-propanol and acetonitrile as anti-solvents at the end of a cooling crystallization process.