Study On The Separation And Purification Of Two Isomorphic Steroids

11α-Hydroxy-16α,17α-epoxyprogesterone (abbreviated as HEP) is an important intermediate for synthesis of hormone pharmaceuticals. In industry, HEP is prepared from 16α,17α-epoxyprogesterone (abbreviated as EP) through bioconversion with low conversion (about 40~45%). The separation and purification of HEP is difficult with low yield and poor product quality. To solve these problems, a systematic study on the separation process of HEP and EP was performed, and three different new processes for separation and purification of HEP have been developed in this thesis. According to the similarity in the molecular and crystal structures of HEP and EP, the solid solution formation of the two steroids when they were crystallized from solution were postulated and then confirmed based on the X-ray diffraction crystal structure determination, thermal analysis and composition analysis of the prepared HEP/EP solid solution crystals. This indicates that several stages or times crystallization is needed to get pure HEP crystals.The solubility of HEP and EP in eight different pure solvents and chloroform-toluene mixed solvents with four different compositions were determined. The effect of relative solubility on the crystal purity was studied. The experimental results show that the bigger the relative solubility of EP to HEP is, the higher the purity of HEP crystals can be obtained. Toluene-chloroform mixed solvents afford the most effective enhancement of HEP crystal purity.Novel separation process was studied and compared. The extractive drowning out crystallization was proposed and successfully used for separation and purification of HEP and EP for the first time. Then, combinative separation processes of leaching with crystallization were proposed. HEP was separated and purified through once leaching and twice recrystallization. The efficiency of purification increased 25~30% compared with the current five times recrystallization in industry.Also a leaching-adsorption process was proposed and showed big potential for industrial application. The leaching-adsorption process was studied in detail. The isothermal adsorption equilibrium of HEP and EP on different adsorbates were determined. Screening of adsorbate, solvent and diluting solvent were performed. Also the adsorption kinetics of HEP and EP on the selected adsorbent were measured. The separation of HEP and EP by fixed bed adsorption was studied. The breakthrough and elution curves were determined, the process parameters were optimized. HEP was purified through once leaching and once following adsorptive separation. The modeling for the fixed bed adsorption was performed and solved. This work affords basic data and important foundation for the scaling up of the process.All the contents above have never been founded in any type documents.