甲基和基的催化酶选择性1,6结合添加物
Fanke Meng1, Xiben Li1, Sebastian Torker1
1Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Nature
|August 2, 2016
概括
这项研究引入了一种新型的有机铜催化剂,用于对二酸盐进行对抗选择性1,6合并添加,其中包含基和基组. 这一突破为复杂分子,包括药品,提供了新的合成途径.
科学领域:
- 有机化学
- 催化剂
- 医学化学
背景情况:
- 在有机合成中,催化酶选择性结合物添加非常重要.
- 对非循环二烯酸盐的 1,6-结合物添加是罕见的,特别是对可功能化的基团,如propargyl或allyl.
- 现有的1,6添加方法在范围和基质兼容性方面是有限的.
研究的目的:
- 开发一种对1,6-结合物添加到非循环二酸盐的催化酶选择方法.
- 将propargyl和2替代的基组纳入二酸盐受体.
- 阐明开发的催化系统的机制和选择性.
主要方法:
- 开发一种用于合添加反应的有机铜催化剂.
- 使用商业上可用的基化合物或单替代基作为核爱物.
- 使用密度函数理论 (DFT) 计算来理解反应机制和选择性.
主要成果:
- 器官铜催化剂有效地促进了对二酸盐的1,6结合基和2-基替代基的添加.
- 获得了高产量 (高达83%),二重选择性 (> 98: 2) 和反选择性 (99: 1).
- 基于催化剂结构的机制研究揭示了位点和酶选择性的起源.
结论:
- 一种新的可访问的有机铜催化剂可以进行高度选择性的1,6-结合物添加.
- 该方法允许将有价值的功能组引入非循环二酸盐.
- 开发的方法已成功应用于抗HIV药物 (-) - equisetin的选择性合成.
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