启用模块化点击化学库,通过对碳酸和氨基酸的顺序结合
Sheng-Cai Wang1, Xiang Zhou1,2, Ying-Xian Li1
1State Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, 510006, Guangzhou, China.
Angewandte Chemie (International ed. in English)
|June 28, 2024
概括
一个新的双击化学策略能够快速合成各种化学库,使用易于获得的构建块. 这种方法促进了药物发现,并产生了对S. aureus和MRSA具有显著抗菌活性的化合物.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 化学生物学 化学生物学
背景情况:
- 高通量合成和选对于药物发现至关重要.
- 点击化学为图书馆构建提供了一个模块化的方法.
- 开发新的点击反应和构建块仍然是一个挑战.
研究的目的:
- 开发一种新的双击策略来合成化学库.
- 为了利用广泛可用的碳素酸和氨基与硫异酸.
- 探索合成化合物的抗菌潜力.
主要方法:
- 序列化和硫化物交换 (SuFEx) 反应.
- 使用硫异酸盐 (FSO2NCO) 作为一个关键试剂.
- 在高产量的合成N-硫胺和N-硫胺.
主要成果:
- 开发了一种用于模块化库合成的双击策略.
- 在N-fluorosulfonyl amides和N-acylsulfamides方面取得了接近量化的产量.
- 展示了从各种原始材料制成的96井板的图书馆建设.
- 鉴定出具有强烈抗菌活性的化合物,可对抗S. aureus和MRSA (MIC ≤6.25μg/mL).
结论:
- 双击策略是有效和强大的图书馆合成.
- 这种方法可以快速访问各种化学实体,用于药物发现.
- 合成的化合物显示出作为新型抗菌剂的前景.
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