一个14-3-3分子成分的 (-) -Cotylenol的合成
Stephen I Ting1, Dylan W Snelson1,2, Tucker R Huffman1,2
1Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|September 8, 2023
概括
研究人员开发了一种针对14-3-3蛋白相互作用 (PPI) 网络的有价值分子 (-) - 胆醇的新10步合成方法. 这种方法可以创建用于治疗研究的相关化合物.
科学领域:
- 有机化学
- 医学化学
- 化学合成
背景情况:
- 调节14-3-3蛋白相互作用的小分子对于治疗和研究工具至关重要.
- 对14-3-3类PPI分子剂的获取是有限的,因此需要新的合成策略.
研究的目的:
- 开发一个实用和简洁的化学合成 (-) -cotylenol.
- 建立一个多功能合成路径,用于生成多种类型的类比物和cotylenin类化合物的库.
主要方法:
- 采用了10个步骤的不对称合成,具有5-8-5核心结构.
- 关键反应包括利贝斯金德-斯罗格尔碎片合和双重克莱森烯级联.
- 使用立体化学和功能化的后期控制.
主要成果:
- 通过开发的10步路径有效合成 (-) - 甲基醇.
- 合成成功地在关键断片合步骤中克服了显著的硬体障碍.
- 双重的克莱森级联有效地构建了八个成员的环.
结论:
- 报告的合成为 (-) - 胆醇和相关分子提供了实用的入口.
- 这一途径为药物发现提供了14-3-3 PPI调节器的探索.
- 该方法适用于结构-活动关系研究的集中图书馆综合.
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