模块化方法用于合成和生物活性分析8,8'-二黄素的8,8'-二黄素
Moritz K T Klischan1, Flaminia Mazzone2, Lena Berning3
1Institute of Bioorganic Chemistry, Heinrich Heine University Düsseldorf, Forschungszentrum Jülich, Stetternicher Forst, Geb.15.8, 52426 Jülich, Germany.
ACS omega
|November 16, 2023
概括
我们用可扩展的铁催化合物合成了55种黄,其中包括新的8,8双黄. 狄米尔类黄类药物表现出增强的生物活性,这表明它们可能成为新药的潜在来源.
科学领域:
- 有机合成 有机合成
- 药用化学 医学化学
- 自然产品 化学 化学
背景情况:
- 黄酸是一种多样化的自然产品类别,具有广泛的生物活性.
- 为探索它们的治疗潜力,开发高效的合成路径到新的黄类结构至关重要.
- 双黄类,黄类的二元体,往往表现出与其单类对应物相比独特和增强的特性.
研究的目的:
- 开发一个可扩展和模块化合成,用于单体和二元类黄类药物的图书馆.
- 研究合成化合物的生物活性,包括细胞毒性,抗菌作用和抗氧化能力.
- 为了识别具有治疗潜在的新型双黄.
主要方法:
- 通过Fe介导的氧化合,区域选择性合成一个四角正替代的乙芬二元中间体.
- 系统地优化合反应,用于多重克尺度生产.
- 评估生物活动,包括对人类细胞系的细胞毒性,对*Toxoplasma gondii*的抗原动物活性和抗氧化能力.
主要成果:
- 成功合成了55种单体和二体黄类药物库,其中包括14种新的8,8'-二黄.
- 证明了关键的Fe介导氧化合步骤的可扩展性,以多基数量.
- 与单体类型相比,观察到8,8'-维度黄类生物活性显著增加.
- 确定了几种具有高选择性指数的双黄,表明强大的抗原动物活性和低细胞毒性.
结论:
- 开发的合成策略使可扩展和模块化访问多种类型的黄胺结构.
- 8,8'-双黄类是具有增强生物活性的一类有前途的化合物.
- 鉴定到的双维诺酸需要进一步调查,因为它们是潜在的药物发现的结构,特别是用于抗原动物的应用.
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