A novel domino approach for synthesis of indolyl tetrahydropyrano [4,3-c]pyrazole derivatives as anticancer agents

作者：Wang, Fu-Qiang; Yang, Hui; He, Bin; Jia, Yong-Kang; Meng, Shi-Yao; Zhang, Chao; Liu, Hong-Min; Liu, Feng-Wu^*

来源：Tetrahedron, 2016, 72(38): 5769-5775.

DOI：10.1016/j.tet.2016.07.078

• Domino reaction
• Indole
• 1,4:3,6-Dianhydrofructose
• 1,4,6,7-tetrahydropyrano[4,3-c]pyrazole
• In-vitro antitumor activity

A series of indolyl substituted 1,4,6,7-tetrahydropyrano[4,3-c]pyrazole derivatives were synthesized via a domino method based on the 1,4:3,6-Dianhydrofructose. The mechanism was proposed and proved by calculation with a density functional theory (DFT), which includes formation of phenylhydrazone, furanone ring opening, Fischer indole synthesis, pyrazole ring closing and a furan ring expansion. In vitro antitumor activity of all synthesized compounds against four human cancer cell lines (MCF-7, EC-109, HGC-27, and PC-3 cell lines) were then evaluated, using MTT assay. We found that most of the compounds were more potent than the positive control 5-fluorouracil. Particularly, compound 4i against HGC-27 and PC-3, 4j against EC-109 cell lines showed three fold greater activity than 5-fluorouracil, respectively. The activity of compounds 4c and 4d against MCF-7 cell line was close to that of doxorubicin.

• 单位
  郑州大学