8-epi-Liphagal的合成研究
Studies on the Total Synthesis of 8-epi-Liphagal
查看参考文献15篇
文摘
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四环杂萜类天然产物Liphagal含有新奇的[6-7-5-6]四环骨架,是磷酸肌醇3-激酶(PI3K)的有效抑制剂之一,可以选择性抑制细胞增殖和促进细胞死亡,在治疗炎症、免疫紊乱、癌症以及心血管疾病中有潜在的医用价值.从廉价的2,4,5-三甲氧基苯甲醛出发,通过Wittig反应、Cu催化的环化反应、选择性氢化、分子内Friedel-Crafts反应,以直线步骤最长7步,8.72%的总收率实现了8-epi-Liphagal高级中间体10的合成. |
其他语种文摘
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The tetracyclic meroterpenoid natural product (+)-liphagal is one of a number of natural inhibitors of phosphatidylinositol 3-kinase (PI3K), which plays a central role in regulation of cell proliferation, cell survival, adhesion, membrane trafficking, glucose transport and neurite growth. Liphagal also shows inhibitory activity against PI3Kα with an IC50 of 100 nmol?L~(-1) making it as an agent for the treatment of inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases. From a structural point of view, liphagal has an unprecedented [6-7-5-6] tetracyclic skeleton, and has attracted significant attention from the synthetic chemists. Starting from cheap and commercially available 2,4,5-trimethoxylbenzaldehyde and α-ionone, an advanced intermediate 10 for the synthesis of 8-epi-liphagal was achieved in the longest linear 7 steps and 8.72% yield. The key reactions include: Wittig reaction, Cu-catalyzed cyclization, chemoselective hydrogenation and Friedel-Crafts reaction. |
来源
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化学学报
,2012,70(21):2232-2235 【核心库】
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DOI
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10.6023/a12090626
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关键词
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8-epi-Liphagal
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天然产物
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合成
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Friedel-Crafts反应
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高级中间体
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地址
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兰州大学化学化工学院, 功能有机分子化学国家重点实验室, 兰州, 730000
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语种
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中文 |
ISSN
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0567-7351 |
学科
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化学 |
基金
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国家自然科学基金
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教育部“111”计划和科技部“973”
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卫生部重大科技专项
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文献收藏号
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CSCD:4754942
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