The solubility of artemisnin in 12 different organic solvents, methanol, ethanol, butanol, acetone, ethyl acetate, isopropyl acetate, acetonitrile, hexane, heptane, 2-butanone (MEK), methyl tert-butyl ether (MTBE), and toluene, as well as in three binary solvent mixtures of ethyl acetate + ethanol, ethyl acetate + acetone, and ethanol + acetone, within the temperature range of (284.10 and 323.15) K, is obtained. The solubility data were fitted to the Two-Liquid-Non-Random (NRTL) activity coefficient equation to obtain the model binary interaction parameters, which were used to predict the solubility of artemisinin in ethyl acetate and acetone or ethanol binary solvent mixtures. The predicted values compared favorably with the experimental data.
The concise synthesis of a potent thrombin inhibitor was accomplished by a mild lactone aminolysis between an orthogonally protected bis-benzylic amine and a diastereomerically pure lactone. The lactone was synthesized by the condensation of l-proline methyl ester with an enantiomerically pure hydroxy acid, which in turn was synthesized by a highly stereoselective (>500:1 er) and productive (100,000:1, S/C) enzymatic reduction of an alpha-ketoester. In addition, a second route to the enantiomerically pure lactone was accomplished by a diastereoselective ketoamide reduction.
For viscous mycelial fermentations it was demonstrated at the pilot-plant scale that the replacement of standard radial flow Rushton turbines with larger diameter axial-flow Prochem hydrofoil impellers significantly improved oxygen transfer efficiency. It was also determined that the Streptomyces broth under evaluation is highly shear thinning. Separate experiments using a Norcardia broth with similar Theological properties demonstrated that the oxygen transfer coefficient, K(L)a, can be greatly increased by use of water additions to reduce broth viscosity. These observations are consistent with the hypothesis that the improvement in oxygen transfer by changing agitator types is primarily due to an improvement in bulk mixing. A model is presented, based on the concepts of Bajpai and Reuss, which explains this improvement in performance in terms of enlargement of the well mixed micromixer region for viscous mycelial broths.
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