A Concise Enantioselective Synthesis and Cytotoxic Evaluation of the Anticancer Rotenoid Deguelin Enabled by a Tandem Knoevenagel/Conjugate Addition/Decarboxylation Sequence.
A Concise Enantioselective Synthesis and Cytotoxic Evaluation of the Anticancer Rotenoid Deguelin Enabled by a Tandem Knoevenagel/Conjugate Addition/Decarboxylation Sequence.
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通过串联knoevenagel/conjugate添加/脱羧序列启用了抗癌棒状果脱脂蛋白的简洁对映选择性合成和细胞毒性评估。
DOI：
10.1039/c3sc50424g
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发表时间：
2013-08
期刊：
影响因子：
8.4
通讯作者：
Scheidt KA
中科院分区：
文献类型：
--
作者：
Farmer RL;Scheidt KA
(−)-Deguelin 是一种鱼藤酸天然产物，具有作为化学预防和化疗剂的巨大潜力。虽然已报道了九角茴香素的几种外消旋合成方法，但仍缺乏对天然和非天然对映体的抗癌活性的正式评估。我们在此描述了灵活且选择性的硫脲催化环化策略在对映选择性全合成德桂林中的成功应用，该策略允许获得任一立体异构体用于生物学研究。合成分六步完成（最长的线性），没有保护基团。对天然产物的两种对映体的评估表明，这些化合物对多种癌细胞系具有有效的抑制作用，但有趣的是，与天然产物相比，非天然 (+)-德桂林优先抑制 MCF-7 乳腺癌和 HepG2 肝癌细胞的生长。
(−)-Deguelin is a rotenoid natural product that possesses significant potential as a chemopreventive and chemotherapeutic agent. While several racemic syntheses of deguelin have been reported, a formal evaluation of the anticancer activity of both the natural and unnatural enantiomers remains lacking. We describe herein the successful application of a flexible and selective thiourea-catalyzed cyclization strategy toward the enantioselective total synthesis of deguelin, which allows access to either stereoisomer for biological studies. The synthesis was completed in six steps (longest linear) with no protecting groups. The evaluation of both enantiomers of the natural product demonstrated potent inhibition of several cancer cell lines by these compounds, but interestingly showed that the unnatural (+)-deguelin preferentially inhibited the growth of MCF-7 breast cancer and HepG2 liver carcinoma cells when compared to the natural product.