Preparation of Synthetic and Natural Derivatives of Flavonoids Using Suzuki-Miyaura Cross-Coupling Reaction.

Martina Hurtová,Josef Cvačka,Kateřina Valentová,Vladimír Křen,David Biedermann,Zuzana Osifová

doi:10.3390/molecules27030967

Abstract

Herein, we report the use of the Suzuki–Miyaura cross-coupling reaction for the preparation of a library of synthetic derivatives of flavonoids for biological activity assays. We have investigated the reactivity of halogenated flavonoids with aryl boronates and with boronyl flavonoids. This reaction was used to prepare new synthetic derivatives of flavonoids substituted at C-8 with aryl, heteroaryl, alkyl, and boronate substituents. The formation of flavonoid boronate enabled a cross-coupling reaction with halogenated flavones yielding biflavonoids connected at C-8. This method was used for the preparation of natural compounds including C-8 prenylated compounds, such as sinoflavonoid NB. Flavonoid boronates were used for the preparation of rare C-8 hydroxyflavonoids (natural flavonoids gossypetin and hypolaetin). A series of previously unknown derivatives of quercetin and luteolin were prepared and fully characterized.

Highlights

Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague, Technická 5, CZ-16628 Prague, Czech Republic
We focused on the preparation of new synthetic derivatives of the flavonoids quercetin (1), luteolin (2), and chrysin (3) substituted on the A-ring with alkyl or aryl substituents using palladium-catalyzed cross-coupling reactions
Varying the amount of base, boronic acid, or palladium catalyst did not affect the result of this reaction

Summary

Introduction

Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague, Technická 5, CZ-16628 Prague, Czech Republic. Quercetin (1; 3,30 ,40 ,5,7-pentahydroxyflavone) is a bioactive flavonol found as a plant pigment mainly in onions, apples, and citrus fruits. It is used as a dietary supplement because it reduces oxidative stress, inhibits low-density lipoprotein oxidation and platelet aggregation, and acts as a vasodilator in blood vessels [2]. Luteolin (2) is known for its anti-allergic and anti-cancer activity [3]. Another flavone, chrysin (3; 5,7-dihydroxyflavone), occurs naturally in many plants, honey, and propolis and exhibits antioxidant, anti-inflammatory, anticancer, and antiviral properties (Figure 1) [4]. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

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