Molecular hybridization-guided 1,3-dipolar cycloaddition reaction enabled pyrimidine-fused spiropyrrolidine oxindoles synthesis as potential anticancer agents

作者：Liu, Xiong-Li; Feng, Ting-Ting; Jiang, Wei-Dong; Yang, Chao; Tian, Min-Yi; Jiang, Yan^*; Lin, Bing; Zhao, Zhi; Zhou, Ying^*

来源：Tetrahedron Letters, 2016, 57(39): 4411-4416.

DOI：10.1016/j.tetlet.2016.08.063

• 1,3-Dipolar cycloaddition reaction
• Adjacent quaternary-tertiary centers
• Molecular hybridization
• Pyrimidine-fused spiropyrrolidine oxindoles
• Antitumor activity

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 I with azomethine ylides (thermally generated in situ from sarcosine and formaldehyde). Products bearing adjacent quaternary-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 vitro evaluation against human lung cancer cells A549, human prostate cancer cells PC-3, and human leukemia cells 1<562 by the MIT-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 1<562, PC-3, and A549, 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.

• 出版日期2016-9-28
• 单位四川轻化工大学; 贵州大学