【摘要】 基于工业色谱法分离制备抗癌药物紫杉醇的半合成前体10-去乙酰紫杉醇(10-DAP)。7-木糖基-10-去乙酰紫杉醇(10-DAXP)在我国特有红豆杉品系(中华红豆杉)枝叶中含量丰富,以其为原料可制备紫杉醇最理想的半合成前体——10-DAP。本研究以部分纯化后的7-木糖基-10-去乙酰紫杉烷为原料,通过β-木糖苷酶水解该粗提物中的主要成分10-DAXP及其两个微量类似物7-木糖基-10-去乙酰三尖杉宁碱(10-DAXC)和7-木糖基-10-去乙酰紫杉醇C(10-DAXP C),脱去其C-7位上的木糖基,水解产物采用大孔吸附树脂吸附,正相快速柱分离和反相制备色谱分离,可获得高纯度的目标物10-DAP,产物纯度为96%,整个工艺的收率大于75%。该方法适合以10-DAXP为原料大规模制备紫杉醇的半合成前体化合物10-DAP,为工业化生产紫杉醇开辟了一条新途径。更多还原

【Abstract】 A scheme for industrial preparative chromatography purification of 10-deacetylpaclitaxel(10-DAP),the semi-synthesized precursor of anticancer drug paclitaxel was developed.7-Xylosyl-10-deacetylpaclitaxel(10-DAXP) is the most abundant constitute in the needles of Taxus Chinensis,a specific yew species distributed in China.10-DAXP has been recognized as a good material to convert into 10-DAP,the most ideal precursor of paclitaxel.The partially purified extract from yew needles which mainly contains 10-DAXP(>60%) and other two minor 7-xylosyl-10-deacetyltaxanes including 7-xylosyl-10-deacetylcephalomannine(10-DAXC) and 7-xylosyl-10-deacetylpaclitaxel C(10-DAXP C),was used as the starting material.The total scheme can be divided into four steps.Firstly,the starting material was hydrolyzed by β-xylosidase to remove the C-7 xylosyl group completely;and then the hydrolyzed products mainly containing 10-DAP were eluted on a column packed with resin to get crude 10-DAP(with the purity of 20.5%) with high yield(96.3%).The crude 10-DAP was purified by a column packed with normal phase,and then by a reversed-phase preparative chromatography with ODS as the solid phase.After these two steps,the purity of the aim product 10-DAP was 96% with the overall yield of 79.7%.This novel scheme was suitable for large-scale purification of 10-DAP from 10-DAXP.更多还原