Low‐Valent Titanium‐Mediated Enantioselective Synthesis of Quinazolinone Alkaloids Circumdatins F, H, and Analogs
Low‐Valent Titanium‐Mediated Enantioselective Synthesis of Quinazolinone Alkaloids Circumdatins F, H, and Analogs
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DOI：
10.1002/cjoc.201400849
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发表时间：
2015-06
影响因子：
5.4
通讯作者：
Shi‐Peng Luo;H. Geng;Yu Wang;Pei‐Qiang Huang
中科院分区：
文献类型：
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作者：
Shi‐Peng Luo;H. Geng;Yu Wang;Pei‐Qiang Huang
本文报道了环切菌素F和H的不含保护基的对映选择性全合成。鉴于喹唑啉酮生物碱类似物在药物研究和发现中的极端重要性，已经合成了四种具有生物活性的喹唑啉苯并二氮杂卓生物碱类似物，包括去甲氧基环孢菌素H（12）和N-去甲基苯并马林素A（13）。该方法基于低价钛促进的酰亚胺与邻硝基苯甲酰亚胺的分子内还原偶联，在温和条件下生成喹唑啉并[3，2-a][1，4]苯并二氮杂卓。此外，已通过NCS介导的脱水环化反应从曲霉素C合成了七环脱氢曲霉素E（16）。
We report the concise and protecting-group-free enantioselective total syntheses of circumdatins F and H. In view of the extreme importance of analogs of quinazolinone alkaloids in drug research and discovery, four analogs of bioactive quinazolinobenzodiazepine alkaloids, including demethoxycircumdatin H (12) and N-demethylbenzomalvin A (13), have been synthesized. The method is based on the low-valent titanium-promoted intramolecular reductive coupling of imides with o-nitrobenzimides, which yielded quinazolino[3,2-a][1,4]benzodiazepines under mild conditions. In addition, heptacyclic dehydraasperlicin E (16) has been synthesized from asperlicin C by a NCS-mediated dehydra-cyclization reaction.