可扩展的皮质素A和相关结构的合成
Jun Shi1, Georg Manolikakes, Chien-Hung Yeh
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|May 5, 2011
概括
研究人员开发了一种可扩展的五步合成,用于皮质素A及其核心结构皮质. 这种改进的方法为进一步的生物研究提供了大量的这些化合物.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 药用化学 医学化学
背景情况:
- 皮质素A是一种复杂的海洋天然产品,具有潜在的治疗应用.
- 之前的皮质素A合成是漫长而具有挑战性的,限制了该化合物的可用性.
- 开发高效的合成途径对于探索皮质素A的生物活性至关重要.
研究的目的:
- 开发一个改进的,可扩展的,实用的合成皮质素A及其核心结构,皮质素.
- 为生物评估提供大量的皮质他,Δ(16) -皮质他A和相关类型.
- 阐明合成方法背后的战略逻辑和演变.
主要方法:
- 使用了五步合成序列.
- 关键反应包括化学选择的双联双质二化,减少的碎片化/捕获/消除一个cyclopropane,和化学选择的化.
- 使用雷尼尼克尔选择性降解 Δ(16) - - 基.
主要成果:
- 皮质素A核心,皮质素,被有效合成.
- 科尔蒂斯丁A成功地从皮质氨酸中制备出来.
- 获得了可扩展量的皮质,Δ(16) -皮质A和类似物.
结论:
- 开发的合成路线简单,可扩展和实用.
- 这种方法促进了用于广泛的生物研究的皮质素A和相关化合物的产生.
- 合成为药物发现工作提供了关键中间体和类似物.
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