瓦尔特烯类化合物的总合成:一种战略性的分子多样性方法
Sachin B Chavan1, Pramod S Wagh1, Abhijeet Kharat1
1Syngenta Biosciences Private Limited, Santa Monica Works, Corlim 403110, Goa, India.
The Journal of organic chemistry
|February 5, 2025
概括
本研究详细介绍了第一个关键的5,6,7,8-四-1H--4-one (THQW) 类中间体和几个复杂的THQW类化合物的总合成. 为了有效地获得这些有价值的化合物,开发了一种多功能合成途径.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 合成化学 合成化学
背景情况:
- 5,6,7,8-四-1H--4-one (THQW) 类家族在很大程度上仍未被探索.
- 这一家族中关键中间体和复杂类化合物的总合成对于进一步的研究至关重要.
研究的目的:
- 报告rac-8-deoxoantidesmone和rac-waltherione M的第一个总合成,THQW类家族的关键中间体.
- 为了实现几个复杂的THQW类化合物的第一个总合成,包括瓦尔特里昂R,8-demethoxywaltherione F,8-demethoxywaltherione R,walindicaone C和walindicaone D.
- 开发一个简洁的三步合成沃尔特里昂F.
主要方法:
- 采用了以多样性为导向的方法,使用了一种多功能中间体:8--5--3-甲基-2-甲基-1H-诺林-4-one.
- 该中间体是由2 - - 5 - - 氨酸和乙基2 - 甲基 - 3 - 氧 - 丁酸盐在一个步骤中合成的.
- 使用MgCl2介导的SNAr反应与基格林纳德试剂生成进一步的中间体.
主要成果:
- 完成了rac-8-deoxoantidesmone和rac-waltherione M的第一个完全合成.
- 实现了沃尔特里昂R,8-demethoxywaltherione F,8-demethoxywaltherione R,瓦林迪卡C和瓦林迪卡D的首次总合成.
- 一个简洁的三步合成瓦尔特里昂F的成功开发.
结论:
- 已经建立了一个通用和高效的合成策略,用于获取THQW类化合物及其关键中间体.
- 这项工作显著扩大了尚未探索的THQW类家族的合成可访问性.
- 开发的方法为合成多种THQW类类似物提供了基础,以便进一步进行生物评估.
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