金属镁催化高张力三元环系的不对称开环反应  

Magnesium catalyzed asymmetric ring-opening reactions of high-strained three membered cyclic systems

作　　者：吕佳明 王林清 王锐[1,2] 杨东旭 Jiaming Lü;Linqing Wang;Rui Wang;Dongxu Yang(Research Unit of Peptide Science(2019RU066),Key Laboratory of Preclinical Study for New Drugs of Gansu Province,School of Basic Medical Sciences,Lanzhou University,Lanzhou 730000,China;Institute of Materia Medica,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100050,China)

机构地区：[1]兰州大学基础医学院,甘肃省新药临床前研究重点实验室,多肽研究创新单元(2019RU066),兰州730000 [2]中国医学科学院,北京协和医学院药物研究所,北京100050

出　　处：《科学通报》2024年第23期3367-3382,共16页Chinese Science Bulletin

基　　金：中国医学科学院医学与健康科技创新工程项目(CIFMS,2019-I2M-5-074,2021-I2M-1-026,2021-I2M-3-001);中央高校项目(lzujbky-2022-ey11,2022-40);甘肃省创新群体项目(20JR5RA310)资助。

摘　　要：利用储量丰富、廉价易得、低污染元素作为催化资源构筑重要立体化学结构具有重要研究意义.含杂原子的手性化合物,例如手性氨基醇类、手性酰胺类、取代四唑类,吲哚衍生物、吡咯烷衍生物等结构单元广泛存在于天然产物中,并且在药物研发过程中具有重要的价值.高效构建以上结构单元一直以来都是化学、生命科学、药学科研工作者重点关注的问题.三元环系结构具有较大的环张力,导致其稳定性低,因此具有较高的反应活性.重要三元环系化合物主要包括:环氧乙烷(oxirane)、氮杂环丙烷(aziridine)以及供体-受体环丙烷(donor-acceptor,D-A cyclopropane),这些结构的不对称开环反应成为构建上述重要结构骨架的合成砌块.值得注意的是,近些年在金属催化剂催化策略下,经三元环类化合物的不对称开环反应高效构建高对映选择性的含杂原子结构片段及杂环骨架受到了广泛的研究关注.同时,伴随了多种催化策略的发展.本文主要综述了近年基于金属镁催化策略的三元环类化合物不对称开环反应研究进展,讨论了基于不同类型亲核试剂及催化条件下的开环反应途径和方法,阐述了反应的相关应用,探讨了部分机理过程.最后,对三元环类化合物不对称开环反应当前的发展状况进行了总结,并在此基础上进行了相关展望.It is of great research significance to construct important three-dimensional skeletons by employing abundant, inexpensive,and easily accessible elements as catalytic resources. Magnesium (Mg) is a usual, non-toxic, readily available andrecyclable alkaline earth metal, which is highly stored in the earth’s crust. So the investigation of the catalytic strategy byusing magnesium element is highly attractive and with highly practical value, on consideration of the problem ofincreasingly prominent shortage of metal resources and the intrinsic demand of sustainable chemistry. In recent years,tremendous endeavors and advances have been made on the development of effective catalysts with abundant metalresources such as magnesium for construction of important three-dimensional skeletons with high level ofenantioselectivities. In the context of organic synthesis, chiral compounds containing heteroatoms, such as chiral aminoalcohols, chiral amides, substituted tetrazoles, indole derivatives, pyrrolidine derivatives and relative structural units, arewidely found in natural products or pharmaceutical compounds, have drawn intense research interest in organic synthesis,life sciences and the discovery of drugs. The three-membered ring structure featured in strong ring tension and alwaysresulted in low stability, so it has higher reactivity compared with other common cyclic ring systems. Important ternarycyclic compounds mainly include: Oxiranes, aziridines, and donor-acceptor cyclopropanes. The desymmetrization orasymmetric ring-opening reaction of these ring systems becomes a powerful synthetic tool for effective construction of theabove important chiral skeletons. Meanwhile, it is worth noting that in recent years, the efficient construction ofheteroatom-containing structural fragments and heterocyclic skeletons with high enantioselectivity through asymmetricring-opening reactions of ternary cyclic compounds under metal-catalyzed strategies has received extensive researchattention. A variety of attractive catalytic strateg

关 键 词：镁催化 氮杂环丙烷 氧杂环丙烷 D-A环丙烷 不对称开环反应 

分 类 号：O621.251[理学—有机化学]