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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
使用药基导向的复合合成策略的拉梅斯瓦里德的总合成
Nathanyal J Truax1, Safiat Ayinde2, Jun O Liu2
1Department of Chemistry & Biochemistry, Baylor University, 101 Bagby Avenue, Waco, Texas 76710, United States.
第一次使用药导向策略实现了拉梅斯瓦里德的全合成. 这种方法使得结构-活性关系的发展成为可能,并确定了一种具有强烈抗癌活性的关键中间体.
科学领域:
- 有机化学
- 医学化学
- 自然产品化学
背景情况:
- 类生物是一种具有潜在生物活性的自然产品.
- 在软珊瑚中发现的Rameswaralide是cembranoid.
- 开发高效的合成途径,使复杂的天然产品成为生物评估的关键.
研究的目的:
- 为了实现拉梅斯瓦拉里德的第一个完全合成.
- 在合成过程中开发结构-活性关系 (SAR) 概况.
- 探索构建复杂多环系统的新型合成策略.
主要方法:
- 药物导向的复合分析.
- 迪尔斯-阿尔德乳化和动态分辨率以进行反选择性合成.
- 开发D环取消策略,包括光催化基循环和迈克尔加法.
主要成果:
- 拉梅斯瓦拉里德的总合成成功.
- 对HCT-116结肠癌细胞具有选择性细胞毒性的三环环氧α-环胺中间体的鉴定.
- 发现了一种氧化状态转换,使α-甲基氨酸部分容易引入.
结论:
- 开发的合成策略对于访问复杂的状结构是有效的.
- 已确定的中间体和双循环β-基因类型具有前景,可作为进一步研究的药.
- 这项工作为探索SAR和开发新的抗癌药物提供了基础.
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