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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
新的合成E7389C14-C35和哈利孔德林C14-C38构建块:双反转方法
Dae-Shik Kim1, Cheng-Guo Dong, Joseph T Kim
1Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
Journal of the American Chemical Society
|October 8, 2009
概括
催化不对称的介导合反应被连续使用,以立体选择性合成E7389和哈利孔德林构件. 这些方法可以有效地构建复杂的分子架构,用于潜在的治疗应用.
科学领域:
- 有机合成 有机合成
- 药用化学 医学化学
- 催化剂是一种催化剂.
背景情况:
- 复杂的天然产品及其类似物,如E7389和哈利孔德林的合成对于药物发现至关重要.
- 复杂的分子框架的立体选择合成在有机化学中提出了重大挑战.
- 介导的合反应为高立体控制的碳-碳键形成提供了强大的工具.
研究的目的:
- 开发和应用顺序的催化不对称的介导合反应,用于关键构建块的立体选择性合成.
- 为了合成E7389C14-C35和哈利孔德林C14-C38碎片.
- 为了证明Ni/Cr和Co/Cr介导合策略的效率和选择性.
主要方法:
- 顺序应用催化不对称的Ni/Cr介导合,形成C19-C20键.
- 随后的催化不对称的Co/Cr介导合构建了C23-C24键,选择性地激活了基化物而不是乙烯化物.
- 使用双反转工艺对C23-O键进行立体选择性构造.
主要成果:
- 在84%的产量中,对E7389 C14-C35构建块22进行立体选择合成.
- 成功合成了C14-C38构建块18b的哈利孔德林.
- 在关键合步骤中实现了高立体选择性 (dr>55:1),证明了该方法的稳定性.
结论:
- 开发的序列催化不对称的Cr介导合反应为复杂的E7389和哈利孔德林构建块提供了有效的途径.
- 该方法展示了不同碳酸键的选择性激活和高立体控制.
- 这种合成策略对于访问具有潜在药物相关性的复杂分子是有价值的.
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