College of Chemistry & Chemical Engineering , Yangzhou University , Yangzhou 225002 , China.
Institute of Translational Medicine, Medical College , Yangzhou University , Yangzhou 225009 , China.
J Org Chem. 2019 Oct 4;84(19):12437-12451. doi: 10.1021/acs.joc.9b01920. Epub 2019 Sep 19.
The acetic acid catalyzed three-component reaction of pyrrolidine, aromatic aldehydes, and 3-arylideneoxindolin-2-ones in refluxing toluene afforded functionalized 7'-arylidenespiro[indoline-3,1'-pyrrolizines] in good yields and with high diastereoselectivity. The similar three-component reaction with 2-arylidene-1,3-indanediones also gave 7'-arylidenespiro[indene-2,1'-pyrrolizines] in good yields. However, the reaction with 3-phenacylideneoxindoles resulted in a mixture of spiro[indoline-3,1'-pyrrolizines] and 7'-arylidene-substituted spirooxindoles in moderate yields. The reaction mechanism included generation of azomethine ylides, β-C-H functionalization of pyrrolidine, and sequential [3 + 2] cycloaddition. The obtained spirooxindole derivatives were investigated by in vitro evaluation against mouse colon cancer cells CT26 and human liver cancer cells HepG2 by MTT assay.
在回流的甲苯中，吡咯烷、芳香醛和 3-亚苄基-2-氧代吲哚啉通过乙酸催化的三组分反应，以良好的产率和高非对映选择性得到了官能化的 7'-亚苄基螺[吲哚啉-3,1'-吡咯嗪]。类似的与 2-亚苄基-1,3-茚二酮的三组分反应也以良好的产率得到了 7'-亚苄基螺[茚-2,1'-吡咯嗪]。然而，与 3-苯甲酰基氧代吲哚啉的反应导致了螺[吲哚啉-3,1'-吡咯嗪]和 7'-芳基取代螺恶唑啉的混合物，产率中等。反应机理包括亚胺叶立德的生成、吡咯烷的β-C-H 官能化和顺序的[3+2]环加成。通过 MTT 测定法，对所得到的螺恶唑啉衍生物进行了体外评估，以评估其对小鼠结肠癌细胞 CT26 和人肝癌细胞 HepG2 的活性。
