Recent Advances in Synthesis of 4-Arylcoumarins

Abstract

4-Arylcoumarins (4-aryl-2H-1-benzopyran-2-one), also known as neoflavones, comprise a minor subclass of naturally occurring flavonoids. Because of their broad-spectrum biological activities, arylcoumarins have been attracting the attention of the organic and medicinal chemistry communities, and are considered as an important privileged scaffold. Since the development of Pechmann condensation, a classical acid-catalyzed condensation between phenol and β-keto-carboxylic acid, several versatile and efficient synthetic approaches for 4-arylcoumarins have been reported. This review summarizes recent advances in the synthesis of the 4-arylcoumarin scaffold by classifying them based on the final bond-formation type. In particular, synthetic methods executed under mild and highly efficient conditions, such as solvent-free reactions and transition metal catalysis, are highlighted.

Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy

“…The main approach to producing 4-arylcoumarins unsubstituted at the hydroxy group is acid-catalyzed Pechmann condensation between resorcinol 4 and ester of β-keto-carboxylic acids 5 [63] (Scheme 1). Using this approach, we synthesized 7-hydroxy-4-arylcoumarins 6a-d with yields of 63-81% by interaction of resorcinol 4 with esters 5a-d (Scheme 1).…”

Palladium‐catalyzed cross‐coupling reactions of coumarin derivatives: An overview

“…[ 44 ] Recently, a review based on the efficient synthetic methods for 4‐arylcoumarins has been reported. [ 45 ]…”

Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin: experimental and computational evidence for intramolecular and intermolecular C–F···H–C bonds

“…The variety of uses of these compounds resulted in an increase in demand for large quantities of coumarins. Due to an insufficient natural supply to meet this demand for these compounds, numerous methods for the synthesis of these compounds have been developed, examples are the Pechmann condensation [10,11], Stille coupling reaction [12], Knoevenagel condensation [13], Heck coupling reaction [14], Kostanecki reaction, Baylis-Hillman reaction [15], Michael reaction [16], Suzuki-Miyaura cross-coupling reaction [17], Negishi cross-coupling reaction [18] and Wittig reaction [17]. The concept of the incorporation of fluorine into organic molecules has gained much interest since Fried and Sabo reported the improvement of the therapeutic index of Scheme 1: Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin (6).…”