Abstract
A series of spirooxindolo-pyrrolidines, pyrrolizidines, and pyrrolothiazoles hybrid compounds were prepared in good yields by regioselective, three-component, 1,3-dipolar cycloaddition reactions between \(\alpha , \beta \)-unsaturated ketones with furanyl substituents and unstable azomethine ylides, which were generated in situ from isatin and various types of amino acids. The synthesized compounds were screened for their antibacterial activities against a spectrum of pathogens. Preliminary studies identified compound 5c as a potent antimicrobial agent against drug-resistant bacteria. In addition, molecular docking studies indicated that compound 5c showed strong interactions with the active sites of lanosterol demethylase, dihydrofolate reductase, and topoisomerase II. This study provides an effective entry to the rapidly construction of a chemical library of heterocycles and compound 5c is one potent antibacterial lead for subsequent optimization.
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Acknowledgments
We wish to thank Professor Xiaokang Liu and Dr. Xiaoli Ji (Sichuan University) for providing an assessment of pharmacological test for all the compounds in this program. We also thank Dr. Jianyou Shi (People’s Hospital of Sichuan province), Dr. Zhihua Mao (Sichuan University) and Professor Jie Li (Zhejiang University) for good suggestions on the NMR and X-ray structure analysis. Financial support from National Natural Science Foundation of China (Nos.81102325, 81001357 and 81273471) and China Postdoctoral Science Foundation (No. 2012T50781) is gratefully acknowledged.
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Wu, G., Ouyang, L., Liu, J. et al. Synthesis of novel spirooxindolo-pyrrolidines, pyrrolizidines, and pyrrolothiazoles via a regioselective three-component [3+2] cycloaddition and their preliminary antimicrobial evaluation. Mol Divers 17, 271–283 (2013). https://doi.org/10.1007/s11030-013-9432-3
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DOI: https://doi.org/10.1007/s11030-013-9432-3