| Supercritical carbon dioxide (CO{dollar}sb2){dollar} is being increasingly used to extract and purify natural product pharmaceuticals because it is inexpensive, safe, and environmentally benign. The work presented in this thesis was conducted to evaluate the ability of both pure and modified supercritical CO{dollar}sb2{dollar} to extract paclitaxel, an anti-cancer agent found in Taxus x. media cv. 'Hicksii' needles, and to purify the Merck & Co. Cozaar{dollar}rmsp{lcub}TM{rcub}{dollar} intermediates, alkylated imidazole and boronic acid. Whereas prior studies chose cosolvents to maximize the amount of paclitaxel extracted from yew needles and bark, this study evaluated the ability of CO{dollar}sb2{dollar} plus a series of cosolvents (hexane, ethyl acetate, tetrahydrofuran, acetonitrile, ethanol, and water) to extract needle fractions of increasing polarity. These studies showed that by pretreating the needles with supercritical CO{dollar}sb2{dollar} and CO{dollar}sb2{dollar} + water, non-polar and polar impurities could be removed. Extracts obtained by contacting pretreated needles with CO{dollar}sb2{dollar} + ethanol were of higher purity (4700 ppm paclitaxel) than extracts obtained by contacting fresh needles with CO{dollar}sb2{dollar} + ethanol (1600 ppm paclitaxel). The amount of paclitaxel extracted using CO{dollar}sb2{dollar} + ethanol was found to depend on particle size. With a particle size of {dollar}<{dollar}841 {dollar}mu{dollar}m, approximately 0.20 mg of paclitaxel was extracted per g of dry needles. The amount increased to 0.30 mg per g of needles when the particle size was reduced to 44-149 {dollar}mu{dollar}m. An internal mass transfer coefficient, {dollar}rm Ksb{lcub}i{rcub}=2.8times10sp{lcub}-7{rcub}{dollar} m/s, was found to best fit the extraction data obtained using 10 mol% cosolvent (ethanol) at 10 MPa and 330 K. The extraction rate increased dramatically when the ground needles were depressurized rapidly.; Supercritical fluids were also used to purify the Cozaar{dollar}rmsp{lcub}TM{rcub}{dollar} intermediates boronic acid and alkylated imidazole. The solubility of alkylated imidazole in CO{dollar}sb2{dollar} ({dollar}{lcub}approx{rcub}10sp{lcub}-4{rcub}{dollar} mole fraction) was determined at two temperatures (310 and 330 K) and eight pressures (10, 12, 13, 15, 20, 30, 45, and 60 MPa). A cross-over region for alkylated imidazole was located at 15 MPa. The solubility of the impurity diol dimer was determined to be on the order of 10{dollar}sp{lcub}-8{rcub}{dollar} mole fraction in supercritical CO{dollar}sb2.{dollar} A purification process which exploited the solubility ratio in CO{dollar}sb2{dollar} of alkylated imidazole and diol dimer was designed to separate the compounds (330 K, 35 MPa). Boronic acid was purified in a similar manner (310 K, 10 MPa) using a supercritical mixture of CO{dollar}sb2{dollar} + diethoxymethane. The boronic acid + tetrahydrofuran solvate was broken using supercritical CO{dollar}sb2.{dollar}... |
