经不对称氨羟基化反应合成多西紫杉醇及其衍生物的新方法研究  

A NOVEL SEMISYNTHESIS METHOD OF DOCETAXEL AND ITS DERIVERTIVE BY ASYMMETRIC AMINOHYDROXYLATION

作　　者：王力元[1] 王蕴峰[1] 齐传民[1] 

机构地区：[1]北京师范大学化学系,北京100875

出　　处：《化工科技》2003年第5期1-6,共6页Science & Technology in Chemical Industry

基　　金：国家自然科学基金资助课题(20171008)。

摘　　要：首次用取代肉桂酸酯和叔丁氧基碳酰胺为原料,经改进的Sharpless不对称氨羟基化反应一步得到了多西紫杉醇及其衍生物的侧链,并最终得到了多西紫杉醇和新型抗癌化合物3,4 亚甲二氧基取代多西紫杉醇,该方法是目前合成多西紫杉醇及其衍生物的最简化和较高收率的路线。研究发现Sharpless不对称氨羟基化反应中手性配体、催化剂的用量和比例对原料的转化率、产物的产率等都有影响,当催化剂K2OsO2(OH)4、手性配体(DHQ)2PHAL的摩尔分数分别为原料的4%和5%时更倾向于生成多西紫杉醇衍生物侧链。所有新化合物及其结构均经过1HNMR、13CNMR、IR、MS、旋光度和元素分析等给予确证。3,4 OCH2O取代多西紫杉醇的初步药理活性显示具有较好的抗癌活性。A novel method was studied to prepare the side chaines of docetaxel and its derivative, with 3,4-OCH_2O substitution benzene ring, through asymmetric aminohydroxylation in one step by using methyl cinnamate as starting material in the first time. Docetaxel and it's the derivative were prepared by the simplified method and with easily handled reaction conditions. The effect of the quantity and molar ratio of chiral ligand, catalyst and starting material on the regioselectivity and yields in the catalytic asymmetric aminohydroxylation was investigated and the optimum conditions were found. The new compounds were identified on the basis of the spectroscopic data. Preliminary pharmaceutical test showed that 3,4-OCH_2O substituted docetaxel has high anticancer activity.

关 键 词：多西紫杉醇 手性配体 Sharpless氨羟基化反应 抗癌活性 抗癌药物 药物合成 

分 类 号：R979.1[医药卫生—药品] R914[医药卫生—药学]