螺旋[cyclopentane-1,3'-oxindole]支架与五个连续的立体中心的酶选择合成
Qiliang Luo1, Tao Mao1, Yao Luo1
1Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China.
Organic letters
|July 22, 2024
概括
一种新的级联无效反应产生具有高立体选择性的复杂螺旋化合物. 这种高效的方法使用了合的易斯酸催化剂,并显示出药物应用的潜力.
科学领域:
- 有机化学 有机化学
- 催化剂是一种催化剂.
- 药用化学 医学化学
背景情况:
- 莫里塔-贝利斯-希尔曼 (MBH) 反应是一种多功能碳-碳键形成反应.
- 伊萨丁和正氧基基是药物化学中重要的异环基架.
- 开发用于复杂分子合成的立体选择方法至关重要.
研究的目的:
- 开发一种高度分立体和分离选择性的级联无效反应.
- 为了合成密集功能化的螺旋[cyclopentane-1,3'-oxindole]化合物.
- 探索合成化合物在药物化学中的潜在用途.
主要方法:
- 使用了一种的N,N'-二氧化物/Mg(II) 复合的易斯酸催化剂.
- 采用了伊萨和正氧基基之间的MBH恶化物之间的级联无效反应.
- 执行DFT计算以阐明反应机制和立体选择性.
主要成果:
- 实现了具有五个连续立体中心的spiro[cyclopentane-1,3'-oxindole]化合物的高度散立体和反选择性合成.
- 证明了广泛的基质范围 (62个示例) 具有高产率 (高达99%) 和出色的立体选择性 (高达>20:1dr,97%ee).
- 观察到连接体加速和性放大效应,并通过格拉姆尺度合成和细胞活力测试证实了潜在的效用.
结论:
- 开发的级联无效反应为有价值的螺旋环化合物提供了一条简洁而有效的途径.
- 奇拉的易斯酸催化剂可以精确控制多个立体中心.
- 合成的化合物具有作为细胞毒性剂的潜力,需要进一步调查.
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