可扩展的总合成和生物评估的haouamine A及其基素
Noah Z Burns1, Irina N Krylova, Rami N Hannoush
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|June 18, 2009
概括
科学家们在格拉姆尺度上合成了海洋类化合物haouamine A,确定了其单一的形体形式,并证实其曲的芳香环是抗癌活性的关键.
科学领域:
- 有机化学 有机化学
- 海洋天然产品 化学 化学
- 药用化学 医学化学
背景情况:
- 胺A是一种复杂的海洋化物,具有独特的曲芳香环结构.
- 胺A的立体化学和生物活性以前一直没有被阐明.
- 总合成为访问和研究复杂的自然产品提供了一条途径.
研究的目的:
- 为了实现克级的胺A的总合成,A.
- 为了确定自然氨酸A的最终的亚特罗皮索米结构,A.
- 研究胺A的结构-活性关系,特别是其曲芳香环在抗癌活性中的作用.
主要方法:
- 开发一种新型的脱方法,使循环赫森能够从点到平面的性转移.
- 合成步骤的格拉姆尺度执行,不包括最终的去保护.
- 合成Atrop-haouamine A,以证实Atropisomeric结果的发生.
- 对PC3细胞进行抗癌活性查.
主要成果:
- 建立了一个可扩展的合成路径,以haouamine A,所有的步骤 (除了最终的降低保护) 执行在一个克尺度.
- 脱的方法允许控制性转移,使得可以编程性体的结果.
- 胺-胺A的合成证实了天然胺A存在于单个稳定的胺体中.
- 生物评估显示,曲的芳香环对于观察到的针对PC3细胞的抗癌活性至关重要.
结论:
- 一个实用的和可扩展的胺A合成已经开发出来.
- 氨酸A的体性质已被确定为确定的.
- 曲的芳香环是胺A的抗癌性质的关键药物.
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