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. 2023 Mar 2;28(5):2304.
doi: 10.3390/molecules28052304.

Hydrogen Bond Assisted Three-Component Tandem Reactions to Access N-Alkyl-4-Quinolones

Huanhuan Liu  1   2 , Huadan Liu  1   2 , Enhua Wang  3 , Liangqun Li  1   2 , Zhongsheng Luo  1   2 , Jiafu Cao  1   2 , Jialin Chen  1   2 , Lishou Yang  1   2 , Xiaosheng Yang  1   2
Affiliations

Hydrogen Bond Assisted Three-Component Tandem Reactions to Access N-Alkyl-4-Quinolones

Huanhuan Liu et al. Molecules. .

Abstract

Hydrogen-bonding catalytic reactions have gained great interest. Herein, a hydrogen-bond-assisted three-component tandem reaction for the efficient synthesis of N-alkyl-4-quinolones is described. This novel strategy features the first proof of polyphosphate ester (PPE) as a dual hydrogen-bonding catalyst and the use of readily available starting materials for the preparation of N-alkyl-4-quinolones. The method provides a diversity of N-alkyl-4-quinolones in moderate to good yields. The compound 4h demonstrated good neuroprotective activity against N-methyl-ᴅ-aspartate (NMDA)-induced excitotoxicity in PC12 cells.

Keywords: N-alkyl-4-quinolones; hydrogen bond; neuroprotective activity; polyphosphate ester; polyphosphoric acid.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Selected bioactive 4-quinolone derivatives.
Scheme 1
Scheme 1
Procedures for the synthesis of 4-quinolones. (a) Synthesis of 4-quinolones. (b) Three-component tandem reactions for the synthesis of N-alkyl-4-quinolones.
Scheme 2
Scheme 2
Experimental and computational mechanistic investigations. (a) Synthesis of N-alkyl-4-quinolone via three-component tandem reaction. (b) Control experiments. (c) DFT calculations.
Scheme 3
Scheme 3
Experimental mechanistic investigations. Reactivity of phosphates (a) and chalcones (b–d).
Figure 2
Figure 2
Concentration-dependent protective effects of 4h. Data are presented as mean ± SD (n = 3). MK-801 was used as positive control. ### p < 0.001 as compared to control group, * p < 0.05, ** p < 0.01, *** p < 0.001 as compared to NMDA group.
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