对α-甲基烯乳酸盐的酶选择性1,3-双极循环添加,以构建螺旋环
Yuji Nishiura1, Kevin J Gonzalez1, Alexander Q Cusumano1
1The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
Organic letters
|August 29, 2023
概括
研究人员开发了一种高效的不对称的1,3-双极循环添加,以创建合的螺旋环异环循环. 这种方法为制药应用提供了高产量和抗选择性.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 不对称的合成方法
背景情况:
- 螺旋环基支架在药物发现中至关重要,以增强制药性质.
- 目前用于酶选择性螺旋环合成的方法有限,需要新的方法.
研究的目的:
- 开发一种高效和enantioselective方法,用于构建性螺旋环异环.
- 探索不对称的1,3-双极循环加法在合成复杂的螺旋环形图案中的应用.
主要方法:
- 不对称的1,3-双极循环加法反应.
- 使用的二乙酸盐或氧化作为1,3-二极.
- 采用α-甲乳酸作为二极化分子在各种环形大小 (6和7个成员) 中.
主要成果:
- 在目标螺旋环异环环中,达到高产率,高达91%.
- 在各种基板上表现出高的反抗选择性,高达89% ee.
- 该方法证明对各种N替代剂和乳酸环大小有效.
结论:
- 报告的非对称循环加法提供了一条可靠的途径,以获得有价值的性螺旋环异循环.
- 这种方法扩大了合成工具包,以获取与药物化学相关的环化合物.
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