Total synthesis and evaluation of C25-benzyloxyepothilone C for tubulin assembly and cytotoxicity against MCF-7 breast cancer cells.
Total synthesis and evaluation of C25-benzyloxyepothilone C for tubulin assembly and cytotoxicity against MCF-7 breast cancer cells.
复制标题
C25-苄氧基埃坡霉素 C 的全合成和评估，用于微管蛋白组装和对 MCF-7 乳腺癌细胞的细胞毒性。
DOI：
10.1016/j.bmcl.2008.07.024
复制
发表时间：
2008
影响因子：
2.7
通讯作者：
Georg,GundaI
中科院分区：
文献类型：
--
作者：
Hutt,OliverE;Reddy,BolluS;Nair,SajivK;Reiff,EmilyA;Henri,JohnT;Greiner,JackF;Chiu,Ting-Lan;Vandervelde,DavidG;Amin,ElizabethA;Himes,RichardH;Georg,GundaI
报道了C25-苄氧基埃坡霉素C的全合成。采用一种新的衍生化C8-C12片段的顺序Suzuki-Aldol-Yamaguchi大环内酯化策略。C25-苄氧基类似物在微管组装和细胞毒性测定中表现出显著降低的生物活性。分子模型模拟表明，C25位置的过量空间体积可能通过破坏对埃坡霉素与β-微管蛋白结合至关重要的关键氢键而降低活性。
The total synthesis of C25-benzyloxy epothilone C is described. A sequential Suzuki–Aldol–Yamaguchi macrolactonization strategy was utilized employing a novel derivatized C8–C12 fragment. The C25-benzyloxy analog exhibited significantly reduced biological activity in microtubule assembly and cytotoxicity assays. Molecular modeling simulations indicated that excessive steric bulk in the C25 position may reduce activity by disrupting key hydrogen bonds that are crucial for epothilone binding to β-tubulin.