对抗真菌的双循环 celogentin C 的总合成
Bing Ma1, Biplab Banerjee, Dmitry N Litvinov
1Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, USA.
Journal of the American Chemical Society
|December 30, 2009
概括
通过使用一种新的左向右策略,实现了塞洛丁C的总合成. 这种双循环八胺表现出抗瘤活性,抑制了精选癌症细胞系的生长.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 类合成 类合成
背景情况:
- 塞洛丁C是一种复杂的双循环八,具有潜在的抗瘤特性.
- 以前使用右向左方法的合成尝试没有成功.
- 为复杂的天然产品开发高效的合成路径对于药物发现至关重要.
研究的目的:
- 为了实现塞洛丁的总合成,C.
- 探索和开发用于构建复杂大循环的新型合成方法.
- 为了评估合成的C. celogentin的抗瘤活性.
主要方法:
- 一个从左到右的合成策略被用于塞洛丁C.
- 关键步骤包括Knoevenagel凝结,激素结合物添加,SmI(2) 介导的缩,以及印-意达氧化合.
- 为了获得最终产品,采用了宏乐和脱保护的步骤.
主要成果:
- 赛洛丁C的总合成成功完成.
- 麦克法迪恩-斯蒂文斯反应的一个轻微的布拉斯劳修饰被确定为有效的缩.
- 使用Pro-OBn作为一种添加剂来控制副产品的形成,优化了英多尔-伊米达的氧化合.
- 赛洛丁C对某些癌症细胞系的生长表现出抑制作用.
结论:
- 开发的左向右合成策略是有效的构建 celogentin C. 的.
- 合成途径为进一步的生物评估提供了塞洛丁C的获取.
- 赛洛丁C作为抗瘤剂显示有前途,需要进一步调查.
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