2016-2015
首页  科学研究  发表论文  2016-2015

DABCO-Catalyzed sp3 C-H Activation: Rapid Access to Isoxazole or Coumarin-Fused 3-Quaternary Carbon Oxindoles and Isoxazole-Fused Pyrrolidinones (Tetrahedron Letters 56 (2015) 5637–5645)

Graphical Abstract

 

ABSTRACT

A facile and efficient methodology was developed for the synthesis of isoxazole or coumarin-fused 3-quaternary carbon oxindoles and isoxazole-fused pyrrolidinones viaDABCO-catalyzed sp3 C-H activation of 5-methyl-isoxazole or 4-methylcoumarin. Furthermore, the biological activity of the isoxazole or coumarin-fused 3-quaternary carbon oxindoles 3 and 5 has been preliminarily demonstrated by in vitroevaluation againsthuman prostate cancer cells PC-3 and human leukemia cellsK562 by the MTT-based assays using the commercially available standard drug Cisplatin as a positive control. These results suggested that most of the compounds 3 and 5 showed considerable cytotoxicities to these two cell lines K562 and PC-3, anda methyl or an ethyl group of acrylates and an oxindole moiety located in the isoxazole-fused 3-quaternary carbon oxindoles 3 are beneficial for the activity. In addition, the activity of all the afforded isoxazole-fused pyrrolidinones 7 were also evaluated against Gram-positive bacteria Staphylococcus aureus (MTCC96) and Gram-negative bacteria Escherichia coli (ATCC25835) using Penicillin as a standard drug for Gram-positive organism or Streptomycin as standard drug for Gram-negative organism. The results demonstrated that most of the compounds 7 hadcomparable in vitro inhibitory activity againstGram-positive bacteria Staphylococcus aureus (MTCC96) with the positive control Penicillin. The results also indicated that isoxazole-fused pyrrolidinone analogs had significantly better inhibition ability against Gram-positive bacteria Staphylococcus aureus (MTCC96) than against Gram-negative bacteria Escherichia coli (ATCC25835).