素的总合成,其七种染色体二聚体,以及关键的部分结构
Ryan C Clark1, Sang Yeul Lee, Dale L Boger
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|August 21, 2008
概括
实现了对p53-MDM2复合体形成的天然抑制剂 - - 罗素的总合成. 这项研究分配了绝对立体化学,并重新分配了其复杂染色体的相对立体化学.
科学领域:
- 自然产品的合成自然产品的合成
- 药用化学 医学化学
- 有机化学 有机化学
背景情况:
- 素是一种p53-MDM2复合体形成的天然抑制剂.
- 它的结构具有一个阿扎菲隆染色体,通过ornithine连接到一个循环.
研究的目的:
- 报告化素的总合成情况.
- 为了赋予化染色体的绝对立体化学.
- 为了重新分配化染色体的相对立体化学.
主要方法:
- 合成阿扎菲隆染色体前体和奥尼丁-氨酸二.
- 凝结反应和一阶段氧化/螺旋循环生成二聚体.
- 用于立体化学分配的光谱分析 (NMR,MS).
- 收总合成方法.收总合成方法.
主要成果:
- 成功合成了染色体-二联的所有八个异体.
- 赋予了天然化染色体的 (4R,8S,9R) 立体化学.
- 证实了立体化学重定位,并确定了化素的绝对立体化学.
- 合成了所有剩余的七种可能的染色体二聚体的克洛夫.
结论:
- 叶绿素的总合成成功完成.
- 绝对和相对立体化学的chlorofusin染色体被最终分配.
- 这项工作为进一步的生物评估提供了各种氧二聚体的获取.
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