BF3-OEt2 Catalyzed C3-Alkylation of Indole: Synthesis of Indolylsuccinimidesand Their Cytotoxicity Studies

Abstract

A simple and efficient BF3-OEt2 promoted C3-alkylation of indole has been developed to obtain3-indolylsuccinimidesfrom commercially available indoles and maleimides, with excellent yields under mild reaction conditions. Furthermore, anti-proliferative activity of these conjugates was evaluated against HT-29 (Colorectal), Hepg2 (Liver) and A549 (Lung) human cancer cell lines. One of the compounds, 3w, having N,N-Dimethylatedindolylsuccinimide is a potent congener amongst the series with IC50 value 0.02 µM and 0.8 µM against HT-29 and Hepg2 cell lines, respectively, and compound 3i was most active amongst the series with IC50 value 1.5 µM against A549 cells. Molecular docking study and mechanism of reaction have briefly beendiscussed. This method is better than previous reports in view of yield and substrate scope including electron deficient indoles.

Efficient enantioselective synthesis of trisubstituted γ-lactam via the Michael addition reaction of 2,3-dioxopyrrolidine with indole in aqueous media

“…8 Similarly, indole is among the most abundant and significant structural motifs in organic synthesis; 9 they are found extensively in biologically active molecules and drugs. 10 Moreover, the scaffold of the indole-Michael product has huge pharmaceutical potential; for example, (−)-clausenamide bioactive natural products are anti-viral hepatitis and anti-Alzheimer's disease agents, 11 and (IPR-1110) 12 and 2 H -pyrrolinone 13 are inhibitors of uPAR protein interactions which could provide valuable chemical probes to further explore the role of the receptor in a range of pathological processes including cancer metastasis particularly in vivo (Scheme 1). 14 Considering the possibilities offered to the catalysts to create specific interactions and induce enantioselectivity, the pharmaceutical potential of an asymmetric Michael addition of 2,3-dioxopyrrolidine and indoles, the polyfunctional nature of the products and the significance of organic reactions in aqueous media make this protocol especially novel and appealing.…”