可扩展的无保护组的雷西布福根因和布法林的总合成
Shaopeng Yu1, Qiuheng Zhang1, Xueqing Zhong1
1The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Organic letters
|November 4, 2024
概括
这项研究提出了七步化学酶合成的resibufogenin和bufalin,避免保护组. 这种新方法有效地从androstenedione (AD) 中产生这些重要的bufadienolides.
科学领域:
- 有机化学 有机化学
- 生物催化剂是一种生物催化剂.
- 药用化学 医学化学
背景情况:
- 雷西布福根因和布法林是具有显著治疗潜力的心脏毒性布法基醇.
- 现有的合成路径通常很长,需要保护组,限制效率.
研究的目的:
- 开发一种高效的resibufogenin和bufalin的化学酶合成.
- 为了建立一个无保护组的路径,为bufadienolide生产.
主要方法:
- 从androstenedione (AD) 开始的化学酶合成.
- 使用基酶P450lun引入一个C14α-基组.
- 立体选择性化和苏苏基交叉合用于C17配置控制.
- 脱水,环氧化和无氧化Mukaiyama水化用于分子的形成.
主要成果:
- 对于resibufogenin和bufalin,已经建立了一个七步合成途径.
- 在整个合成过程中,成功地避免了保护组.
- 在C17的立体化学控制是通过定向化实现的.
- 得到的resibufogenin和bufalin都具有很高的效率.
结论:
- 开发的化学酶策略提供了对resibufogenin和bufalin的简化和高效访问.
- 这种无保护组的方法代表了布法迪埃诺利德合成的重大进步.
- 这种方法对这些有价值的化合物的可扩展生产具有前景.
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