使用三阻碍象限双二催化剂进行高度选择性的不对称化
Garrett Hoge1, He-Ping Wu, William S Kissel
1Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA. garrett.hoge@pfizer.com
Journal of the American Chemical Society
|May 13, 2004
概括
一种新的催化剂 (5) 能够使氨基酸衍生物和制药前体的高度选择性不对称化. 与现有的催化剂相比,这种方法在大规模合成方面具有优势.
科学领域:
- 有机化学 有机化学
- 不对称的催化剂.
- 药用化学 医学化学
背景情况:
- 的配体和金属复合物对于选择性合成至关重要.
- 催化剂在不对称的化反应中被广泛使用.
- 对于制药品来说,有效合成体纯化合物至关重要.
研究的目的:
- 合成一种新型复合物的两个反体 (5).
- 在不对称化中评估复合体5的酶选择性.
- 为了比较催化剂5a与Rh-Me-DuPhos在大规模合成中的有效性.
主要方法:
- 联结体2和复合物的合成 5.复合物的合成
- 状高性能液体染色学 (HPLC) 用于反体分离.
- 阿尔法乙胺脱氨基酸 (6a-e) 和普雷加巴林前体 (8) 的不对称化.
主要成果:
- 成功合成了连接物2和复合物的两个反体5.
- 复合物5在化反应中表现出高选择性 (>99% ee).
- 催化剂5a在前体8的大规模化方面比Rh-Me-DuPhos具有优势.
结论:
- 新型的复合体5,具有阻碍象限,实现了优异的反选择性.
- 这种催化剂对于氨基酸衍生物和制药前体的不对称化是有效的.
- 催化剂5a为工业规模的不对称化提供了一个有希望的替代品.
相关概念视频
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