紫杉醇侧链衍生物合成及其抗肿瘤活性

Synthesis and Antitumor Activity of Side Chain Derivatives of Paclitaxel

利用3-酰胺基取代氧化吲哚与乙醛酸酯发生Aldol反应,合成了系列未见文献报道的紫杉醇侧链苯基异丝氨酸衍生物3a^3h,产率在71%~99%之间,研究了取代基的空间位阻效应对反应非对映选择性的影响。采用1H NMR,13C NMR和HRMS对化合物3a^3h进行结构表征。化合物3a^3h对人肺癌细胞株(A549)和人白血病细胞株(K562)的抑制活性采用MTT法进行测定。体外抗肿瘤活性研究表明:化合物3a^3h对K562和A549细胞株均有抗增殖活性,其中化合物3b、3f、3g和3h对K562具有较好的抑制活性;化合物3b、3c和3f对A549具有较好的抑制活性。

A series of unreported side chain phenylisoserine derivatives of paclitaxel(3 a ~ 3 h) were synthesized through the Aldol reaction,with 3-acylamino oxindole and aldehyde ester as leading compounds. The yield was 71 % ~99 % and the effects of substrate substituents on the diastereoselectivity were discussed. The structure of 3 a ~ 3 h were characterized by1 H NMR,13 C NMR and HRMS. Their anti-proliferative activities in vitro against human leukemia cells K562 and human lung cancer cells A549 were evaluated by the standard MTT assay. The pharmacological activity results showed that this kind of compounds had anti-proliferative activity against human cancer cells K562 and A549,compounds 3 b,3 f,3 g and 3 h had better inhibitory activity on K562 cell,3 b,3 c and 3 f had better inhibitory activity on A549 cell.