康普勒斯塔丁的总合成:开发一种Pd(0) 介导的因多尔取消剂,用于宏循环化
Hiroyuki Shimamura1, Steven P Breazzano, Joie Garfunkle
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|May 18, 2010
概括
研究人员开发了一种以催化的醇取消用于宏循环,在完整合成中实现了高选择性. 这种方法为复杂分子构造提供了改进的第二代方法.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 药用化学 医学化学
背景情况:
- 康普莱斯塔丁和 хлоропептинII是复杂的天然产品,具有紧张的16个成员的双环系统.
- 之前的合成策略在宏循环化过程中面临着控制人类选择性方面的挑战.
研究的目的:
- 开发和检查用于宏循环的分子内 ((0)) 介导的醇取消.
- 定义影响completstatin合成中的选择性因素.
- 为了在第二代的complestatin总合成中实现这种方法.
主要方法:
- 内部分子 (((0) -催化道废除 (拉洛克循环化).
- 开发第二代完全合成的complestatin与逆转宏循环的顺序.
- 在二环形成中对atropodiastereoselectivity的分析.
主要成果:
- 基质36的拉洛克循环化产生了对自然 (R) 配置具有高选性 (>20:1) 的产物37.
- 与第一代合成相比,逆转的宏循环化顺序和基质复杂性并没有阻碍,而是改善了体选择性.
- 观察到的随机选择性与在类似的木二烯合器中观察到的二烯选择性形成了对比.
结论:
- 催化印解消是一种强大的工具,用于构建具有高atropocontrol. strained biaryl宏循环.
- 这种第二代合成提供了一个高效和高度选择性的途径来完成statin.
- 该研究强调了反应策略在复杂分子合成中实现所需立体化学结果的重要性.
相关概念视频
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Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
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