一个循环加法级联方法来实现 (-) -FR18287777的总合成
David A Evans1, Jeremy T Starr
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. evans@chemistry.harvard.edu
Journal of the American Chemical Society
|October 30, 2003
概括
研究人员使用醇反应和跨管迪尔斯-阿尔德反应实现了细胞毒性天然产物 (-) -FR182877的不对称合成. 这种方法有效地构建了复杂的五环结构和七个新的立体中心.
科学领域:
- 有机化学 有机化学
- 自然产品的合成自然产品的合成
- 不对称的合成方法
背景情况:
- (-) -FR182877是一种具有复杂结构的细胞毒性天然产品.
- 开发高效的合成路径以复杂的自然产品是化学生物学和药物发现的关键.
研究的目的:
- 为了实现自然产品的不对称合成 (-) -FR182877.
- 使用立体选择性反应来确定整个结构的性.
- 探索跨环的迪尔斯-阿尔德反应在构建多环系统中的实用性.
主要方法:
- 利用 (4R) -4 - - 基-2-oxazolidinone介导的醇反应来建立奇拉性.
- 采用区域选择性的苏苏基合物用于宏观循环形成.
- 通过氧化β-基托,启动了一个立体选择性的跨环的迪尔斯-阿尔德反应级联.
主要成果:
- 成功合成了细胞毒性天然产物 (-) -FR182877.
- 使用醇反应建立了性,并形成了19个成员的宏碳循环.
- 跨环的迪尔斯-阿尔德反应级联形成了四个新的环和七个新的立体中心.
结论:
- 开发出了 (-) - FR182877 的高效不对称合成.
- 这项研究突出了醇和跨环Diels-Alder反应在复杂分子合成中的力量.
- 半经验计算为迪尔斯-阿尔德级联的立体化学结果提供了洞察力.
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