| Pharmacologically active substance containing chiral centers can exist as pairs of enantiomers, which exhibit the same physical properties but show a different molecular conformation. In general , only one of enantiomers is biologically active or possesses pharmacological relevance, the resolution of enantiomers is of great importance for the pharmaceutical industry. Supercritical CO2 extraction might provide an alternative method for the resolution of racemates, as this possibility was briefly investigated by Fogassy et al. The purpose of this thesis was to demonstrate the knowledge of solubility behavior , the usefUlness of SEE and to investigate the influence of some parameters upon the resolution process. Determination of chiral extractant solubility into supercritical CO2 is indispensable for both fUndamental and practical viewpoints. In this thesis, the solubilities of eight chiral compounds which are ephedrine, phenylalanine, malic acid, camphorsulfonic acid, tartaric acid, mandelic acid, 5-hydroxytryptophan, pseudoephedrine, and two pairs diastereomeric bases which are ephedrine-tartaric acid, pseudoephedrine-tartaric acid , were measured over temperature and pressure ranges of 25C0-55C0 and 6.5-20.Mpa. The results show that there exist critical phenomena in solubility behavior, the solubility near critical pressure is higher than far from critical point; the critical phenomena may be able to be subscribed by solubility parameters; the relation between the solubility and density of CO2 was investigated, the linear relationship between InS and lnp is clearly observed; an empirical method for predicting solubility solely as a function of temperature and pressure is developed. Results demonstrate that differences in solubility of diastereomeric bases, it might be able to extract ephedrine and pseudoephedrine from the diastereomeric bases mixtures. As it was demonstrated by the resolution of the racemic pseudoephedrine, CO2 density and resolving agent can influence the extraction process. tartaric acid is a good resolving agent, it was showed that a high degree of resolution (100%e.e.) can 3 be achieved within a single extraction step . Dibenzoyl-L-tartaric acid and DTTA which are ramifications of tartaric acid , had remarkable partial resolutions, while other resolving agents such as malic acid, phenylalanine, camphorsulfonic acid had poor partial resolutions at the same condition. In the standard ecperiments, the racemic pseudoephedrine was allowed to react with 0.5 equivaient of the chiral agents. Extraction at 0.25,0.50,0.75, and 1.0 molar ratios of (2S,3S)-(-)-Tartaric acid have shown that an increase of the molar ratio didn抰 result in enhanced enantiomeric excess, there was a optimizing ratio. Molecular force calculation showed that R-acid exception of DTTA prefers to reacting with S-pseudoephedrine. That was comported with experimental results. With the increasing of temperature and pressure(50C0, I OMpa) , epimerization was found in tartaric acid resolution . phenylalanine had poor resolution but caused pseudoephedrine epimerization. These phenomena have not been reported. Electrophoretic separations were carried out with uncoated fused-silica capillaries of 60cm * 50j.~m ID. (Waters Capillary Ion Analyzer USA). Before initial use, the capillary was washed successively with basic solutions, water and running buffer. Buffer solution consisted of 0.025M Tri... |
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