Total synthesis and biological evaluation of (-)-exiguolide analogues: Importance of the macrocyclic backbone
Total synthesis and biological evaluation of (-)-exiguolide analogues: Importance of the macrocyclic backbone
复制标题
(-)-exigigolide 类似物的全合成和生物学评价：大环主链的重要性
DOI：
10.1039/c3ob40131f
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Hiroshi Kubo
中科院分区：
文献类型：
--
作者：
Haruhiko Fuwa;Kana Mizunuma;Makoto Sasaki;Takaya Suzuki;Hiroshi Kubo
从海绵Geodia exigua中分离的（-）-阿瓜替尼（1）已显示出在体外抑制A549人肺腺癌和NCI-H460人肺大细胞癌细胞的生长。在这项研究中，我们合成了1的结构类似物，以探索其骨架结构与活性的关系，并发现C18甲基和C16-C17双键的构型对1的有效抗增殖活性很重要。此外，我们制备了一系列的侧链类似物的1通过多样化的后期阶段的中间体，我们的全合成，并发现，三烯侧链的1可以在一定程度上进行修改，而没有显着的损失的活动，提供了一个刘易斯基本杂原子被放置在末端。
(−)-Exiguolide (1), isolated from the marine sponge Geodia exigua, has been shown to inhibit the growth of the A549 human lung adenocarcinoma and NCI-H460 human lung large cell carcinoma cells in vitro. In this study, we synthesized structural analogues of 1 to explore its skeletal structure–activity relationships and found that the C18 methyl group and the configuration of the C16–C17 double bond of 1 are important for the potent antiproliferative activity. Furthermore, we prepared a series of side-chain analogues of 1 by diversification of a late-stage intermediate of our total synthesis, and found that the triene side chain of 1 could be modified to some extent without significant loss of activity, provided a Lewis basic heteroatom is placed at the terminus.