【作者】 孙倩；

【导师】 任其龙；

【作者基本信息】 浙江大学 ， 化学工艺， 2007， 硕士

【摘要】 d-α-生育酚琥珀酸酯作为天然α-生育酚的酯化衍生物在保健品市场具有很大的前景，同时也是一种有效的癌症辅助治疗药物。本文研究了d-α-生育酚琥珀酸酯包括制备，分离纯化，结晶等过程的工艺。首先，对于d-α-生育酚琥珀酸酯的制备，采用含量较高的天然α-生育酚作为原料，与琥珀酸酐酯化，以三乙醇胺作为催化剂，在正己烷溶剂中进行反应。通过考察初始原料比，催化剂用量，溶剂用量，反应温度等条件对酯化反应的影响。结合前期实验结果确定酯化的条件为反应时间为4小时，反应温度为90℃，琥珀酸酐／天然α-生育酚为2(mol／mol)，三乙醇胺／天然α-生育酚是0.06(mL／g)，正己烷／天然α-生育酚为2.5(mL／g)。工艺条件优化后，α-生育酚的转化率在96％以上，d-α-生育酚琥珀酸酯的收率在93％以上。本文分别研究了采用硅胶和树脂两种固定相柱层析法分离纯化d-α-生育酚琥珀酸酯。先是采用硅胶作为固定相，以实验室自制品为原料，确定层析条件为：层析介质为100～200目粗孔Ⅱ号，洗脱液为氯仿甲醇梯度洗脱，流量为2mL／min，室温，上样量为3g d-α-生育酚琥珀酸酯粗品／40g硅胶，上样浓度为0.38g／mL。此时，柱层析产物含量能从原料60％左右提高至78％以上，回收率达到90％以上。然后采用树脂作为固定相层析分离纯化d-α-生育酚琥珀酸酯，通过筛选，选定大孔吸附9号树脂作为固定相，无水甲醇作为流动相，流量为2mL／min，柱温为30℃，上样量为3g d-α-生育酚琥珀酸酯粗品／100mL树脂，上样浓度为0.25g／mL。此时，柱层析产物含量能从原料68％左右提高至85％以上，部分流份收集时含量能达到90％以上。回收率在90％以上。本文还通过包括溶剂的选择，结晶速率的考察等研究，对于d-α-生育酚琥珀酸酯的结晶做了初步研究。更多还原

【Abstract】 As the derivative of J-α-tocopherol, d -α-tocopheryl succinate is stable, and has anticancer effect. Therefore it is promising in the field of medicine. In this paper, we studied the preparation, separation and crystallization of J-α-tocopherol succinate.Firstly, we studied the preparation of d -α-tocopheryl succinate, we use high content d -α-tocopherol and succinate anhydride as raw materials, triethanolamine as the catalyst, n-hexane as the solvent, J-α-tocopherol succinate was prepared. Effects of various conditions were studied. The optimum conditions were molar ratio of d-α-tocopherol to succinate anhydride 1:2, the ratio of n-hexane volume to J-α-tocopherol 2.5 mL/g, the ratio of triethanolamine to d-α-tocopherol 0.06 mL/g, reaction temperature 90℃ and reaction time 4 h. The conversion of J-α-tocopherol was about 96%, and the yield of J-α-tocopherol succinate was about 93%.Then we purified the d-α-tocopheryl succinate through column chromatography. Silica gel column chromatography and macroporous adsorbed resin column chromatography were applied. The optimum conditions of silica gel column chromatography were as follows: chloroform and methanol were used as mobile phases, the load of sample 3 g/40 g silica gel (100-200 mesh), the flow rate 2 mL/min, room temperature, the concentration in the mobile phase 0.38 g/mL. The purity of d -α-tocopheryl succinate increased to 78% from 60% with recovery 90% at optimum conditions. By using macroporous adsorbed resin column chromatography, we chose macroporous adsorbed resin No.9 as solid phase, and methanol was used as mobile phases. The optimum conditions of macroporous adsorbed resin column chromatography were as follows: the flow rate 2 mL/min, temperature 30℃, the load of sample 3 g/100 mL resin, the concentration in the mobile phase 0.25 g/mL. The purity of d -α-tocopheryl succinate increased to more than 85% with recovery more than 90% at optimum conditions.We also studied the crystallization of d -α-tocopheryl succinate including the solvents selection, temperature decreasing rate and so on.更多还原