一个简洁,高效和可扩展的Thapsigargin和Nortrilobolide从 (R) -
1Department of Chemistry, Queen's University , 90 Bader Lane, Kingston, Ontario K7L 3N6, Canada.
Journal of the American Chemical Society
|April 20, 2017
概括
从 (R) - - - - 卡开发出一种新合成的thapsigargin和nortrilobolide. 这种高效的五步方法可使这些复杂的酸和相关化合物的可扩展生产.
科学领域:
- 有机化学
- 合成化学
- 医学化学
背景情况:
- 塔普西加林和诺特里洛博利德是具有显著生物活性的复杂天然产品.
- 自然来源的有限可用性阻碍了研究和治疗应用.
- 预药Mipsagargin在癌症治疗中显示出前途, 需要可扩展的合成.
研究的目的:
- 开发一个简洁,高效,可扩展的thapsigargin和nortrilobolide的总合成.
- 建立一个实用的合成途径来获取这些生物活性酸乳及其类型.
- 为了使Mipsagargin用于临床试验和潜在的治疗用途.
主要方法:
- 一个由自然碳-碳键形成的5步合成策略.
- 基因化以建立分子复杂性.
- 用于构建六酸乳骨架的二重选择性皮纳科尔循环.
主要成果:
- 从商业上可获得的 (R) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 的成功合成.
- 显示了一个高度功能化的乳骨架结构.
- 开发的策略可用于合成结构模拟物和相关化合物.
结论:
- 开发的合成提供了一种实用且可扩展的途径,用于thapsigargin,nortrilobolide和Mipsagargin.
- 这种方法解决了这些化合物的有限自然供应和高需求.
- 这种合成策略有助于进一步探讨thapsigargin家族的治疗潜力.
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