总合成的 (-) -laulimalide 的总合成
Paul A Wender1, Sayee G Hegde, Robert D Hubbard
1Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. wenderp@stanford.edu
Journal of the American Chemical Society
|May 2, 2002
概括
研究人员合成了 (-) -laulimalide,这是一种海洋衍生化合物,它破坏了蛋白聚合并诱导了亡. 这种高效的合成为laulimalide和相关药物类似物提供了一条新的途径.
科学领域:
- 海洋天然产品化学 海洋天然产品化学
- 有机合成 有机合成
- 化学生物学是化学生物学.
背景情况:
- (-) - Laulimalide 是一种来自海洋海绵的新型宏化物.
- 它通过促进异常的蛋白聚合和亡,表现出强大的抗癌活性.
- 它的作用方式类似于Taxol (R),在克服多种药物耐药性方面具有潜在的优势.
研究的目的:
- 开发一个灵活和融合的 (-) -laulimalide 的非对称合成.
- 建立一个有效的生产laulimalide和其类似物以进行进一步研究的途径.
主要方法:
- 合成采用了一种二分体选择性萨库拉伊反应.
- 一个不受保护的邻近二醇的区域选择性宏观细菌化是一个关键步骤.
- 整体合成涉及25个步骤 (最长的线性) 和36个步骤整体.
主要成果:
- (-) - - 劳利马利被成功合成.
- 合成实现了3.5%的总产量.
- 该路线特别短且高效,促进了模拟合成.
结论:
- 已经确定了 (-) - laulimalide 的新且高效的不对称合成.
- 这种合成途径提供了laulimalide及其类似物,对于探索其治疗潜力至关重要.
- 合成突出了关键反应,如Sakurai反应和复杂分子构建的宏观活性化.
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