Department of Organic Chemistry, Shahid Beheshti University, G.C., Tehran 1983963113, Iran.
Department of Chemistry, Jouybar Branch, Islamic Azad University, Jouybar, Iran.
Org Biomol Chem. 2023 Mar 8;21(10):2143-2161. doi: 10.1039/d2ob02311c.
In the present study, a library of important enantiopure dispirooxindole [indolizidine, pyrrolizidine, and pyrrolidine] derivatives with three or four contiguous and two quaternary stereogenic centers using different amino acids (pipecolic acid, sarcosine, proline and hydroxyproline) were synthesized in high yields (up to 96%) through a regio- and diastereoselective (up to 99 : 1) multicomponent 1,3-dipolar cycloaddition strategy. Based on the results, the alteration of amino acids led to a change in the regioselectivity and unusual regioisomers (pyrrolizidine indolizidine/pyrrolidine) were obtained to construct a novel enantiopure 1,3-dispirooxindole skeleton. The stereochemical outcome of the cycloaddition was determined by single crystal X-ray diffraction analysis and the self-disproportionation of enantiomers (SDE) test confirmed the enantiomeric purity of the desired products. The mechanism and differences in the regioselectivity of the 1,3-dipolar cycloaddition reactions between the stable azomethane ylides obtained from ninhydrin, pipecolinic acid, and proline with ()-2-oxoindolin-3-ylideneacetyl sultam were theoretically studied through DFT calculations at the M06-2X/6-31G(d,p) level in methanol.
在本研究中，使用不同的氨基酸（哌啶酸、肌氨酸、脯氨酸和羟脯氨酸），通过区域和立体选择性（高达 99:1）的多组分 1,3-偶极环加成策略，以高产率（高达 96%）合成了具有三个或四个连续和两个季立体中心的重要手性全反式二螺[吲哚里嗪、吡咯里嗪和吡咯烷]衍生物库。基于这些结果，氨基酸的改变导致了区域选择性的变化，并获得了不寻常的区域异构体（吡咯里嗪 吲哚里嗪/吡咯烷），从而构建了新型手性全反式 1,3-二螺环氧化吲哚骨架。环加成的立体化学结果通过单晶 X 射线衍射分析确定，并且外消旋体的自拆分（SDE）测试证实了所需产物的对映体纯度。通过在甲醇中在 M06-2X/6-31G(d,p)水平上进行的 DFT 计算，理论研究了从邻苯二酮、哌啶酸和脯氨酸获得的稳定吖丙啶叶立德与（）-2-氧代吲哚啉-3-亚基乙酰基磺酰胺之间 1,3-偶极环加成反应的区域选择性的机制和差异。
