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Reaction of 5-alkoxy-3,4-dihalo-2(5H)-furanones with secondary amines: expected versus unanticipated products and their preliminary bioactivity investigations

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Abstract

Using KF as base and THF as solvent, 5-alkoxy-3,4-dihalo-2(5H)-furanones were reacted with secondary amines. The normal products, β-amino-2(5H)-furanones, were obtained via the tandem Michael addition-elimination reaction as expected in most cases. However, the reaction between diisopropylamine and 3,4-dihalo-5-methoxy-2(5H)-furanones yielded unanticipated products, methyl (E)-2-halo-4-(diisopropylamino)-4-oxobut-2-enoates. The possible synthetic mechanism involving a rearrangement reaction was proposed. The biological activity assay of products derived from the reactions of 5-alkoxy-3,4-dihalo-2(5H)-furanones with different amino compounds was preliminarily investigated by the MTT method on A549 cells in vitro, which revealed that some derivatives of amino acid esters with a benzene ring exhibited the best anticancer bioactivity.

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Notes

  1. Some literature on alkoxy migration (especially involving in the 1,4-methoxy migration and the migration on five-membered rings).

  2. Some literature involving the formation of different propadienones.

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Acknowledgements

The authors are grateful to the National Natural Science Foundation of China (no. 20772035) and the Natural Science Foundation of Guangdong Province (no. 5300082) for the financial support of this work. We also thank Dr. Guo-Liang Li and Dr. Li-Ming Fang for helpful discussions.

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Authors and Affiliations

  1. Department of Chemistry, School of Chemistry and Environment, South China Normal University, Guangzhou, 510006, People’s Republic of China

    Yang-Qing Mo, Zhao-Yang Wang, Jian-Hua Fu, Yue-He Tan & Shi-He Luo

  2. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of China

    Wen-Jie Mei

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Correspondence to Zhao-Yang Wang.

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Mo, YQ., Wang, ZY., Mei, WJ. et al. Reaction of 5-alkoxy-3,4-dihalo-2(5H)-furanones with secondary amines: expected versus unanticipated products and their preliminary bioactivity investigations. Monatsh Chem 143, 443–453 (2012). https://doi.org/10.1007/s00706-011-0594-3

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