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异马巴里干三聚酸的总合成
Yaroslav D Boyko1, Christopher J Huck1, David Sarlah1
1Roger Adams Laboratory, Department of Chemistry , University of Illinois , Urbana , Illinois 61801 , United States.
Journal of the American Chemical Society
|August 27, 2019
概括
研究人员首次完成了对细胞毒性异马巴里干三聚酸,拉布酸A和星酸E的总合成. 这一突破为获取这些具有挑战性的海洋天然产品提供了总体战略.
科学领域:
- 有机化学
- 自然产品合成
- 医学化学
背景情况:
- 伊斯莫拉巴里干三类是一种因其高细胞毒性而闻名的海洋天然产品.
- 复杂而紧张的跨-syn-trans-perhydrobenz[e]indene核心是一个重要的合成挑战.
- 这些化合物的先前合成是有限的或不成功的.
研究的目的:
- 实现第一个 (±) - 拉巴酸A和 (±) - 星E的总合成.
- 开发一种用于合成异马巴里干三类的通用和有效策略.
- 探索用于构建复杂多环结构的新型合成方法.
主要方法:
- 一个14步线性合成从商业geranylacetone.
- 采用了减少的基聚烯循环形成核心结构.
- 采用了前所未有的氧化Rautenstrauch循环化.
- 包含一个p-toluenesulfonylhydrazone的缩α-替代与现场的降解转换.
- 在侧链建设中应用了后期的交叉合.
主要成果:
- 成功合成了 (±) - 拉巴酸A和 (±) - 恒星素E.
- 有效地构建了特征性压力转-syn-trans-perhydrobenz[e]indene核心.
- 展示了合成多种多不和侧链的模块化方法.
- 制定了适用于其他异马巴里干家族成员的总体策略.
结论:
- 开发的合成途径是高效和通用的,用于进入具有挑战性的海洋三体.
- 这些新的方法为复杂分子合成开辟了新的途径.
- 这项工作使以前无法获得的细胞毒性海洋天然产品可用于进一步的生物研究.
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