基激活 Pd (II) -催化 γ-C (sp) -H 原生氨基酸的乳酸化
Shuang Liu1, Zhe Zhuang1, Jennifer X Qiao2
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|December 16, 2021
概括
这项研究引入了一种新的催化方法,用于直接从氨基酸中合成γ-乳酸. 这种高效的方法提供了一条精简的途径,以获得像莱纳利多米德类似物这样的有价值的制药构件.
科学领域:
- 有机化学
- 医学化学
- 催化剂
背景情况:
- 在许多药物中,包括免疫调节性胺基药物 (IMiDs) 和布里瓦拉类药物中,γ-乳酸是关键的结构基因.
- 目前的合成途径往往涉及多个步骤,限制了这些有价值的化合物的效率和可访问性.
- 氨基酸的直接分子内γ-C-H氨基化为从丰富的氨基酸前体中构建γ-乳酸核提供了一个有吸引力的替代方案.
研究的目的:
- 开发一种新的,高效的方法,用于直接合成γ-乳酸盐,异因多林和2-imidazolidinones.
- 探索由催化的氨基酸衍生氨基酸的分子内 γ-C-sp3-H 乳化.
- 建立一个实用且对环境无害的协议,使用易于获得的原材料.
主要方法:
- 使用了一种新型的2-皮里联体启用 ((II)) 催化反应.
- 使用N-氨基酸作为指导组和循环合作伙伴.
- 作为反应中唯一的氧化剂使用了三甲基氧化物 (TBHP).
主要成果:
- 通过Pd(II) 催化γ-C(sp3) -H乳化成功合成了γ-乳,异印和2-imidazolidinones.
- 证明了C6替代对2-皮里配体的关键作用,以有效地形成乳.
- 展示了开发的协议的广泛基板范围.
结论:
- 开发的协议提供了从氨基酸前体中获取有价值的γ-乳酸基因的方便和直接途径.
- 该方法的实用性通过莱纳利多米德模拟物和布里瓦拉塞坦的两步合成得到验证.
- 这种方法为药物化学中传统的多步合成提供了一个实用且潜在的绿色替代方案.
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