病毒性毒素B及其类型的总合成:战略演变,结构修订和生物评估
K C Nicolaou1, Christopher R H Hale, Christian Nilewski
1Department of Chemistry, §Department of Biochemistry and Cell Biology, and ∥Department of Ecology and Evolutionary Biology, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
Journal of the American Chemical Society
|October 16, 2014
概括
研究人员实现了病毒性毒素B的总合成,修改了其结构并开发了新的化学反应. 这一突破使得创建类似的抗菌药物发现.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 化学合成 化学合成
背景情况:
- 病毒毒素B是一种复杂的四环素抗生素,具有具有挑战性的结构.
- 之前的综合努力在构建关键结构特征和引入必要的功能组时遇到了困难.
研究的目的:
- 为了实现病毒性毒素B的总合成,B.
- 开发用于构建复杂分子的新型合成方法.
- 修改最初分配的病毒性毒素B的结构.
- 探索对抗细菌病原体的病毒性毒素类型的结构-活性关系.
主要方法:
- 化和易斯酸介导的螺旋环化反应的发展,以形成EF螺旋连接.
- 迈克尔-迪克曼反应用于A和C环结构的应用.
- 逐步氧化策略 (以和酸为基础) 用于在C4a和C12a上安装基.
- 合成和生物评估的viridicatumtoxin类似物.
主要成果:
- 成功的病毒性毒素B的总合成,导致了修订的结构分配.
- 建立有效的方法来形成受阻的EF螺旋连接,并设置A和C环.
- 为特定的碳位置开发新型氧化技术.
- 鉴定了针对细菌菌株,包括耐药病原体的病毒性毒素类型的第一个结构-活性关系.
结论:
- 完成了病毒毒素B的总合成,验证和完善合成策略.
- 开发了新的化学反应,扩大了复杂分子合成的工具包.
- 修订后的病毒性毒素B的结构为未来的研究提供了基础.
- 合成的类似物显示出抗菌药物开发的潜力,为结构-活性关系提供了洞察力.
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