链状的总合成和立体化学分配
Nicholas A Isley1, Yusuke Endo1, Zhi-Chen Wu1
1Department of Chemistry and Skaggs Institute for Chemical Biology , The Scripps Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 , United States.
Journal of the American Chemical Society
|October 3, 2019
概括
作为一个复杂的宏循环天然产品,链的首次全合成证实了其独特的氨酸-氨酸交叉链结构. 这种合成澄清了立体化学,确定了天然产品中存在的正确的3R氨酸二聚体.
科学领域:
- 自然产品的合成自然产品的合成
- 有机化学 有机化学
- 药用化学 医学化学
背景情况:
- 链 (1) 是2015年发现的一种宏环天然产品.
- 它具有不寻常的翻译后修改,将氨酸和氨酸残留物联系在一起.
- 这种独特的结构形成了一个20个成员的循环.
研究的目的:
- 为了实现第一个全合成链.
- 为了确认氨酸-托方交叉链的区域化学.
- 为了明确地分配在lysine-2的C3中心的立体化学.
主要方法:
- 使用Pd(0) 介导的醇取消用于宏循环.
- 采用催化C-H激活/β-化,使用高价 (III) 基质.
- 为立体化学分配合成了3R和3S氨酸二聚体.
主要成果:
- 成功合成了链,证实了交叉链接的拟议区域化学.
- 确定天然产品含有3R氨酸二聚体,而不是之前分配的3S.
- 为进一步的生物研究提供了链的获取.
结论:
- 总合成验证了链的独特结构特征.
- 已经确定了氨酸残留的正确立体化学.
- 这项工作使未来的研究能够研究链状蛋白和相关化合物的生物学作用.
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