Synthesis of a Coumarin-Based Analogue of Schweinfurthin F.
Synthesis of a Coumarin-Based Analogue of Schweinfurthin F.
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DOI：
10.1021/acs.joc.1c02046
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发表时间：
2021-12-03
期刊：
影响因子：
--
通讯作者：
Wiemer DF
中科院分区：
文献类型：
--
作者：
Schroeder CM;Dey PN;Beutler JA;Wiemer DF
天然瑞草精是一种具有显著抗增殖活性的二苯乙烯类化合物，其作用机制尚不确定。为了获得与天然结构偏差最小的荧光类似物，将香豆素环体系环化到d环上，形成了一种新的schweinfurin f的类似物。该二苯乙烯通过会聚合成，采用Horner-Wadsworth-Emmons缩合形成中心二苯乙烯烯烃。在对经典的Arbuzov反应进行了最近的更有效的改进后，制备了三环膦酸盐，并试图与适当取代的双环醛进行缩合，但香豆素体系无法在反应条件下生存。当烯烃生成先于香豆素生成时，二苯乙烯的生成顺利进行，并最终允许获得目标香豆素基schweinfurin类似物。这种类似物在美国国家癌症研究所的60个细胞系生物测定中显示出所需的荧光特性和显著的生物活性，这种生物活性的模式反映了天然产物schweinfurthin F.这种方法可以方便地获得天然schweinfurthin的新的荧光类似物，也应该适用于其他天然二苯乙烯。
The natural schweinfurthins are stilbenes with significant antiproliferative activity and an uncertain mechanism of action. To obtain a fluorescent analogue with minimal deviation from the natural structure, a coumarin ring system was annulated to the D-ring, creating a new analogue of schweinfurthin F. This stilbene was prepared through a convergent synthesis, with a Horner–Wadsworth–Emmons condensation employed to form the central stilbene olefin. After preparation of a tricyclic phosphonate via a recent and more efficient modification of the classic Arbuzov reaction, condensation was attempted with an appropriately substituted bicyclic aldehyde but the coumarin system did not survive the reaction conditions. When olefin formation preceded generation of the coumarin, the stilbene formation proceeded smoothly and ultimately allowed access to the targeted coumarin-based schweinfurthin analogue. This analogue displayed the desired fluorescence properties along with significant biological activity in the National Cancer Institute’s 60-cell line bioassay, and the pattern of this biological activity mirrored that of the natural product schweinfurthin F. This approach gives facile access to new fluorescent analogues of the natural schweinfurthins and should be applicable to other natural stilbenes as well.
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影响因子：
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影响因子：
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影响因子：
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