2016-2015
首页  科学研究  发表论文  2016-2015

1,3-dipolar cycloaddition enabled isoxazole-fused spiropyrrolidine oxindoles syntheses from 3-methyl-4-nitro-5-alkenyl-isoxazoles and azomethine ylides(Tetrahedron 2016, 72, 1364-1374)

Graphic Abstract 

 

  

ABSTRACT

Afacile and efficient methodology was developed for the synthesis of isoxazole-fused spiropyrrolidine oxindoles 3-5via a 1,3-dipolar cycloaddition reaction of 3-methyl-4-nitro-5-alkenyl-isoxazoles with azomethine ylides (thermally generated in situ from isatin derivatives and proline or thioproline or sarcosine). Products bearing adjacent quaternary-tertiary centers were smoothly obtained in high yields (up to 90% yield) with good diastereoselectivity (up to 20:1). Furthermore, their biological activity has been preliminarily demonstrated by in vitroevaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562by the MTT-based assays using the commercially available standard drug Cisplatin as a positive control. These results suggested that most of isoxazole-fused spiropyrrolidine oxindoles3-5 showed considerable cytotoxicities to these three cell lines K562,A549 and PC-3, and that isoxazole-fused spiropyrrolidine oxindoles may be potential leads for furtherbiological screening.