2016-2015
首页  科学研究  发表论文  2016-2015

A facile and efficient synthesis of polycyclic spiropyrrolidine oxindoles bearing mesityl oxide unit via a three-component 1,3-dipolar cycloaddition reaction(Tetrahedron 2015, 71, 8131-8139)

Graphic Abstract

 

  

  ABSTRACT

A facile and efficient methodology was developed for the synthesis of multifunctional polycyclic spiropyrrolidine oxindoles bearing mesityl oxide unit via a three-component 1, 3-dipolar cycloaddition reaction ofdienones 2 with azomethine ylides (thermally generated in situ from isatin derivatives and proline or thioproline).Products bearing adjacent four chiral carbon centers were smoothly obtained in high yields (up to 98% yield) with diastereoselectivities up to >20:1. Furthermore, the key structural characteristic of the products of such a reaction is the natural product ingredient turmerone motif fused at the 3-position of the spirooxindole core, with varying degrees of substitution around it. In addition, their biological activity has been preliminarily demonstrated by in vitroevaluation againsthuman prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cellsK562 by the MTT-based assays, using the commercially available standard drugs Cisplatin as a positive control. These results suggested there is a trend that lipophilicity groups improve the potency, and also suggested an mesityl oxide moietylocated in the polycyclic spiropyrrolidine oxindoles is beneficial for the activity. The results also demonstrated that most of the compounds showed considerable cytotoxicities to these three cell lines K562, A549 and PC-3, and indicated that polycyclic spiropyrrolidine oxindole analogs bearing mesityl oxide unit may be potential leads for furtherantitumor activity screenings.