2016-2015
首页  科学研究  发表论文  2016-2015

Molecular hybridization-guided 1,3-dipolar cycloaddition reaction enabled pyrimidine-fused spiropyrrolidine oxindoles synthesis as potential anticancer agents(Tetrahedron Letters 57 (2016) 4411–4416)

 Graphic Abstract

 

 

  ABSTRACT

Reported is a facile and efficient methodology toward the synthesis of novel pyrimidine-fused spiropyrrolidine oxindoles via a multicomponent 1,3-dipolar cycloaddition reaction of pyrimidine-fused 3-alkenyloxindoles 1 with azomethine ylides (thermally generated in situ from sarcosine and formaldehyde).Products bearing adjacentquaternary-tertiary centers were smoothly obtained in high yields (up to 90% yield) with good diastereoselectivity (up to >20:1). In addition, their biological activity has been preliminarily demonstrated by in vitroevaluation againsthuman lung cancer cells A549, human prostate cancer cells PC-3 and human leukemia cellsK562 by the MTT-based assays, using the commercially available broad-spectrum anticancer drug of Cisplatin as a positive control.The results also demonstrated that most of the compounds showed considerable cytotoxicities to these three cell lines of K562, PC-3 andA549, showed comparably potent or even more potent than the positive control of Cisplatin (up to 3.0 times), and indicated that novel pyrimidine-fused spiropyrrolidine oxindoles may be potential leads for further biological screenings and may generate drug-like molecules.