(-) - 拉索诺利德A的总合成
Barry M Trost1, Craig E Stivala1, Daniel R Fandrick1
1Department of Chemistry, Stanford University , Stanford, California 94305-5080, United States.
Journal of the American Chemical Society
|August 23, 2016
概括
研究人员实现了拉索诺利德A的总合成,这是一种具有抗癌性质的新型多基化物. 他们开发了一种关键合反应的新方法,有利于线性产物并实现高效的合成.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 化学生物学 化学生物学
背景情况:
- 拉索诺利德是新型的多基化物,在体外表现出显著的抗癌活性.
- 拉索诺利德A的复杂结构是一个合成的挑战.
研究的目的:
- 开发一种正式的合成拉索诺利德A.
- 为拉索诺利德A建立一个融合合成策略.
- 为了研究和控制Ru-催化基-基合的选择性.
主要方法:
- 融合合成利用两个复杂的碎片.
- 催化 - - 基合反应.
- 一个β-ketoester的酶催化动态动态减少.
主要成果:
- 成功完成了拉索诺利德A的正式和随后的总合成.
- 通过基质修饰在Ru催化合中证明了对线性与分支产品选择性的控制.
- 工程酶在β-ketoester降解中实现了高的反反选择性.
结论:
- 开发的合成途径提供了进入拉索诺利德A的途径.
- 这项研究促进了对Ru催化合反应的理解和应用.
- 酶工程为立体选择性合成提供了一个强大的工具.
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