基于催化剂的帕泰胺A和DMDA-PatA的总合成
Chun-Xiang Zhuo1, Alois Fürstner1
1Max-Planck-Institut für Kohlenforschung , D-45470 Mülheim/Ruhr , Germany.
Journal of the American Chemical Society
|July 31, 2018
概括
一种新合成的胺A及其类似物DMDA-Pat A为研究提供了这些细胞毒性化合物. 该方法使用一种新的铁催化反应来创建关键的二酸盐结构,使药物发现的可扩展生产成为可能.
科学领域:
- 海洋天然产品化学
- 有机合成
- 药物化学
背景情况:
- 帕泰胺A和DMDA-Pat A是强大的细胞毒性化合物.
- 这些化合物有望治疗黑色素瘤和白血病.
- 供应有限阻碍了详细的生物评估.
研究的目的:
- 开发一种新的,可扩展的胺A和DMDA-PatA合成途径.
- 为了进一步进行生物评估和药物开发.
主要方法:
- 一个不合常规的策略使用2-pyrone中间体.
- 铁催化环开放/交叉合形成Z,E-酸盐.
- 黄金催化剂用于前体合成和静态合用于侧链形成.
主要成果:
- 实现了短时间的,强大的,可扩展的胺A和DMDA-Pat A合成.
- 该战略有效地构建了具有挑战性的二氧化基结构.
- 合成可以很容易地从pateamine A转向DMDA-Pat A.
结论:
- 开发的合成途径克服了帕泰胺A和类似物供应的限制.
- 这项工作有助于进一步研究它们的治疗潜力.
- 机械洞察力是通过研究三碳烯复合物获得的.
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