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Synthesis and chemical reactivity of novel polyhydroxylated bis-chalcones
* 1 , 2 , 2 , 1, 3 , 1
1  LAQV-REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
2  LAQV-REQUIMTE and Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
3  Faculty of Agrarian Sciences and Environment, University of the Azores, 9700-042 Angra do Heroísmo, Açores, Portugal.
Academic Editor: Alfredo Berzal-Herranz


Chalcones, a class of compounds characterized by two aromatic rings linked through a three carbon α,β-unsaturated carbonyl system, arouse widespread interest related to their (bio)synthesis and broad biological activities. However, less attention has been given to a subcategory of chalcones, bis-chalcones, despite some studies suggesting that they have improved bioactivities in comparison to their mono derivatives. Their synthesis is relatively less explored and typically requires longer reaction times and harder purifications, especially for derivatives with free hydroxy groups. This issue is relevant because several activities of bis chalcones have been associated to the presence of hydroxy groups in the structure.

In this context, the objectives of this work were to establish an efficient methodology for the synthesis of novel polyhydroxylated bis-chalcones and bis-chalcones containing other substituent groups such as halogen, methoxy, and prenyl groups and explore their chemical reactivity for further transformation into other potentially bioactive flavonoids.

Herein, we report our most recent results on the synthesis of bis-chalcones and their transformation into bis-flavones. Bis-chalcones were obtained in good yields (50-80%) by basic catalyzed Claisen–Schmidt condensation of MOM/Me-protected bis-acetophenones with aromatic aldehydes, followed by deprotection of MOM groups in an acidic medium. In turn, a prenylated bis-chalcone was prepared by O-prenylation of the hydroxylated bis-acetophenone followed by Claisen rearrangement and Claisen–Schmidt condensation with 4-methoxymethylbenzaldehyde. After, some unprotected bis-chalcones were successfully cyclized into bis-flavones through cyclodehydrogenation with I2/DMSO. In the future we intend to evaluate the anti-inflammatory activity of these compounds.

Keywords: bis-chalcones; flavonoids; synthesis; Claisen–Schmidt condensation; cyclodehydrogenation