基杜宁的简要化学酶合成
Jian Li1, Fang Chen1, Hans Renata1
1Department of Chemistry, BioScience Research Collaborative, Rice University, Houston, Texas 77005, United States.
Journal of the American Chemical Society
|October 12, 2022
概括
研究人员首次实现了复杂的D-seco limonoid, gedunin的新合成. 在合成化学领域的这一突破为开发针对热冲击蛋白90 (HSP90) 的新药提供了潜力.
科学领域:
- 有机合成
- 医学化学
- 自然产品合成
背景情况:
- 类药物是具有显著药用潜力的复杂天然产品.
- 有效的合成途径使D-seco limonoids保持完整或环形仍然具有挑战性.
- 基杜宁是一种环状D-seco体,具有90热冲击蛋白 (HSP90) 抑制作用.
研究的目的:
- 报告第一个复杂环D-seco limonoid的新合成, gedunin.
- 建立一个通用的合成策略,
主要方法:
- 一个13步合成序列被设计和执行.
- 现代催化转化被用来构建关键的四元中心.
- 在C3位置使用生物催化氧化来引入功能.
主要成果:
- 首次成功合成基杜宁.
- 合成策略有效地确定了复杂的碳循环核心和A环基因.
- 开发的方法为更广泛的氧化提供了途径.
结论:
- 报告的合成代表了进入复杂的体的重大进步.
- 这一战略开辟了用于治疗应用的格杜宁类同类和相关化合物的探索途径.
- 合成方法可能有助于发现新的HSP90抑制剂.
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