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Review
. 2017 Jun 28;117(12):7762-7810.
doi: 10.1021/acs.chemrev.7b00020. Epub 2017 May 10.

Chalcone: A Privileged Structure in Medicinal Chemistry

Chunlin Zhuang  1 , Wen Zhang  1 , Chunquan Sheng  1 , Wannian Zhang  1   2 , Chengguo Xing  3 , Zhenyuan Miao  1
Affiliations
Review

Chalcone: A Privileged Structure in Medicinal Chemistry

Chunlin Zhuang et al. Chem Rev. .

Abstract

Privileged structures have been widely used as an effective template in medicinal chemistry for drug discovery. Chalcone is a common simple scaffold found in many naturally occurring compounds. Many chalcone derivatives have also been prepared due to their convenient synthesis. These natural products and synthetic compounds have shown numerous interesting biological activities with clinical potentials against various diseases. This review aims to highlight the recent evidence of chalcone as a privileged scaffold in medicinal chemistry. Multiple aspects of chalcone will be summarized herein, including the isolation of novel chalcone derivatives, the development of new synthetic methodologies, the evaluation of their biological properties, and the exploration of the mechanisms of action as well as target identification. This review is expected to be a comprehensive, authoritative, and critical review of the chalcone template to the chemistry community.

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Conflict of interest statement

Notes

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Structures of chalcone and two clinically approved chalconebased drugs.
Figure 2.
Figure 2.
Electron push–pull pairs for fluorescent chalcones.
Figure 3.
Figure 3.
Representative fluorescent chalcones.
Figure 4.
Figure 4.
Flavokawains A (58) and B (59).
Figure 5.
Figure 5.
Structures of chalcones as NF-κB inhibitors.
Figure 6.
Figure 6.
Structures of chalcones as TrxR inhibitors
Figure 7.
Figure 7.
Structures of chalcones as Nrf2 activators
Figure 8.
Figure 8.
Representative antimicrotubule chalcones.
Figure 9.
Figure 9.
Structures of TUB chalcones and cocrystal structure of TUB092 with tubulin [generated using PyMol (http://www.pymol.org/)].
Figure 10.
Figure 10.
Structures of chalcones as ALR2 and COX inhibitors.
Figure 11.
Figure 11.
Structures of boron-containing chalcones.
Figure 12.
Figure 12.
Structures of coumarin–chalcones
Figure 13.
Figure 13.
Structures of indole–chalcones.
Figure 14.
Figure 14.
Structures of chalcone–quinoxalines
Figure 15.
Figure 15.
Other representative fused chalcone hybrids
Figure 16.
Figure 16.
Amide-linked chalcones
Figure 17.
Figure 17.
Diol-linked chalcones
Figure 18.
Figure 18.
Ester- or ether-linked chalcones
Figure 19.
Figure 19.
1,2,3-Triazole linked chalcones
Figure 20.
Figure 20.
Other representative linked chalcones.
Figure 21.
Figure 21.
Phthalocyanine–chalcone conjugates
Figure 22.
Figure 22.
Chalcones targeting tubulin predicted by computational strategy.
Figure 23.
Figure 23.
Other representative chalcones for target identification by computational strategy.
Scheme 1.
Scheme 1.
Biosynthesis of Chalcones and Downstream Pathways
Scheme 2.
Scheme 2.
Claisen–Schmidt Condensation of Chalcone
Scheme 3.
Scheme 3.
Suzuki Coupling for Chalcone Synthesis
Scheme 4.
Scheme 4.
Suzuki–Miyaura Coupling for Chalcone Synthesis
Scheme 5.
Scheme 5.
Heck Coupling and Carbonylative Heck Coupling for Chalcone Synthesis
Scheme 6.
Scheme 6.
Wittig Reaction for Chalcone Synthesis
Scheme 7.
Scheme 7.
Julia–Kocienski Olefination for Chalcone Synthesis
Scheme 8.
Scheme 8.
Other Cross-Couplings for Chalcone Synthesis
Scheme 9.
Scheme 9.
Friedel–Crafts Acylation for Chalcone Synthesis
Scheme 10.
Scheme 10.
Photo-Fries Rearrangement for Chalcone Synthesis
Scheme 11.
Scheme 11.
One-Pot Synthesis of Chalcones
Scheme 12.
Scheme 12.
Synthesis of cis-Chalcones
Scheme 13.
Scheme 13.
Michael Addition of a Chalcone with Cysteine
Scheme 14.
Scheme 14.
Sulfa-Michael Addition of Chalcones
Scheme 15.
Scheme 15.
Aminohalogenation of Chalcones
Scheme 16.
Scheme 16.
Asymmetric Michael Addition of Malonates/Malononitriles to Chalcones
Scheme 17.
Scheme 17.
Other Michael Additions of Malonates to Chalcones
Scheme 18.
Scheme 18.
Michael–Mannich Domino Reaction
Scheme 19.
Scheme 19.
Asymmetric Oxa-Michael–Michael Addition of trans-Nitrostyrene (43) to 2-Hydroxychalcones
Scheme 20.
Scheme 20.
[2 + 2]-Cycloaddition of 2-Aminomalonates to Chalcones
Scheme 21.
Scheme 21.
Enantioselective Cross-Reactions of Different Enones: Synthesis of Cyclohexanone
Scheme 22.
Scheme 22.
Annulation of p-Methoxycinnamaldehyde with Chalcones
Scheme 23.
Scheme 23.
Epoxidation and Aziridination of Chalcones
Scheme 24.
Scheme 24.
Synthetic Strategy of Fused Chalcone Hybrids
Scheme 25.
Scheme 25.
Structural Formula of 4-Hydroxyderricin and the ABPP
Scheme 26.
Scheme 26.
Structural Formula of Xanthohumol and the ABPP
Scheme 27.
Scheme 27.
Structural Formula of PAL Chalcones
Scheme 28.
Scheme 28.
Structural Formula of Piperlongumine and Proposed Strategy
See this image and copyright information in PMC

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