Cao Weilun, Dong Junmin, Pan Xuan, Liu Zhanzhu
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
Molecules. 2025 Jul 29;30(15):3164. doi: 10.3390/molecules30153164.
In this article, an efficient and straightforward protocol for the construction of complex dispirocyclic skeletons via regioselective intramolecular Michael addition is presented. Diverse dispirocyclic compounds were synthesized under mild and transition-metal-free conditions with good to excellent yields. Most stereoisomers were conveniently separated by column chromatography, and their relative configurations were identified by single-crystal X-Ray diffraction of representative compounds. A scale-up experiment validated the practicality of this method. In an in vitro assay, some dispirocyclic compounds exhibited potent cytotoxicity with an IC value of 10 mol/L.
本文介绍了一种通过区域选择性分子内迈克尔加成构建复杂双螺环骨架的高效简便方法。在温和且无过渡金属的条件下合成了多种双螺环化合物，产率良好至优异。大多数立体异构体可通过柱色谱方便地分离，其相对构型通过代表性化合物的单晶X射线衍射确定。放大实验验证了该方法的实用性。在体外试验中，一些双螺环化合物表现出强大的细胞毒性，IC值为10 μmol/L。
