总合成,结构修订和 (+) - 雅塔基米的绝对配置
Mark S Tichenor1, David B Kastrinsky, Dale L Boger
1Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
作为一种强大的抗瘤天然产品,雅塔克辛的总合成揭示了结构上的错误分配. 正确的结构,1,通过合成得到证实,建立了它的绝对配置.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 自然产品 自然产品
背景情况:
- 雅塔克米辛是一种强大的抗瘤天然产品,于2003年首次报告.
- 之前的雅塔克米辛结构分配是基于初始合成努力和光谱数据.
研究的目的:
- 详细介绍一个拟议的雅塔凯米辛结构的总合成 (2).
- 调查合成化合物和天然产品之间的差异.
- 为了重新制定和确认雅塔凯米辛的正确结构.
主要方法:
- 拟议的雅塔克辛类型的总合成 (2和3).
- 用于结构阐明的光谱分析 (NMR,MS).
- 立体选择合成以确认绝对配置.
主要成果:
- 结构2的总合成与自然产品没有相关性.
- 光谱分析导致了重制的结构3 (甲基).
- 进一步对结构1进行重新配方,并结合了另一种右侧子单元,通过合成两个反体 (+) -1 和ent-(-) -1,证实了这一点.
- 雅塔克米辛的绝对配置已经明确确确定的.
结论:
- 最初报告的雅塔克米辛的结构是不正确的.
- 雅塔基米的正确结构被提出为1.
- 总合成证实了yacakemycin的结构和绝对配置,有助于未来的药物开发.
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