Synthesis and structure-activity relationship study of FD-891: Importance of the side chain and C8-C9 epoxide for cytotoxic activity against cancer cells
Synthesis and structure-activity relationship study of FD-891: Importance of the side chain and C8-C9 epoxide for cytotoxic activity against cancer cells
复制标题
FD-891 的合成和构效关系研究：侧链和 C8-C9 环氧化物对癌细胞细胞毒活性的重要性
DOI：
10.1038/ja.2015.148
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发表时间：
2016
影响因子：
3.3
通讯作者：
N. Kanoh
中科院分区：
文献类型：
--
作者：
T. Itagaki;A. Kawamata;M. Takeuchi;K. Hamada;Y. Iwabuchi;T. Eguchi;F. Kudo;T. Usui;N. Kanoh
描述了 FD-891 类似物的统一合成及其构效关系。通过使用立体选择性烯丙基化/巴豆酰化和埃文斯醇醛化学，合成了具有不同长度和末端的六个侧链片段。这些片段与大环内酯片段偶联，这里也开发了大环内酯片段的改进合成，以生成 FD-891 和五个截短的类似物。这些合成化合物以及从基因破坏的禾谷链霉菌突变体发酵中获得的三种类似物进行了针对 HeLa 细胞的体外细胞毒活性测试。结果发现，C8-C9 环氧化物和侧链末端的共存对于细胞毒活性至关重要。
Unified synthesis of FD-891 analogs and their structure–activity relationship are described. By using stereoselective allylation/crotylation and Evans aldol chemistry, six side-chain fragments having different length and terminus were synthesized. These fragments were coupled with a macrolactone fragment, improved synthesis of which was also developed here, to generate FD-891 and five truncated analogs. These synthetic compounds as well as three analogs obtained from fermentation of gene-disrupted Streptomyces graminofaciens mutants were tested for in vitro cytotoxic activity against HeLa cells. As a result, coexistence of the C8–C9 epoxide and side-chain terminus was found to be critical for the cytotoxic activity.