通过高效的非对称化,实现了伊克萨贝皮隆及其类型的融合总合成
1Chemistry and Chemical Engineering Guangdong Laboratory, Shantou, China.
Chemistry (Weinheim an der Bergstrasse, Germany)
|December 28, 2024
概括
开发了一种新的13步合成ixabepilone和类似物. 这种方法有效地使用不对称化和阿尔多尔反应创建关键的性中心,从而实现可扩展的生产.
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:
- 伊克萨贝皮隆是一种复杂的宏循环乳类比的epothilone B.
- 它作为微管稳定剂,表现出强大的抗癌活性.
- 在ixabepilone合成中的挑战包括控制多个立体中心和宏循环.
研究的目的:
- 报告ixabepilone及其类型的融合总合成.
- 开发一个可扩展和高效的合成路线.
- 探索复杂的天然产品合成的新型合成方法.
主要方法:
- 收合成策略. 收合成策略.
- 不对称化用于性中心安装 (C3-O,C8-C,C15-N).
- 碎片合的关键阿尔多尔反应.
- 由一个重的基基团控制的新型RCM (环闭转化) 反应.
主要成果:
- 在13步最长的线性序列中实现了总合成.
- 不对称的化产生了高达95%的产量和99%的E.E.
- 阿尔多尔反应提供了高产量和多重选择性 (8:1 d.r. ) 的情况.
- 三个关键片段的格拉姆尺度准备工作取得了成功.
- 新的RCM反应促进了易于合成艾克萨贝皮隆和类似物.
结论:
- 开发的合成路线是高效和可扩展的.
- 该方法允许轻松合成ixabepilone和各种类似物.
- 这项工作为基于ixabepilone支架的进一步药物发现和开发提供了一个有价值的平台.
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