Synthesis and Anti-Rhinovirus Properties of Fluoro-Substituted Flavonoids

Abstract

Fluoro-substituted flavones and 2-styrylchromones, related to natural and synthetic flavonoids previously described, were prepared, characterized and tested for anti-rhinovirus activity. Structural elucidation of the new compounds was performed by IR, NMR spectra and X-ray crystal structure analysis for 6-fluoro-3-hydroxy-2-styrylchromone. The antiviral potency was evaluated by a plaque reduction assay in HeLa cell cultures infected with rhinoviruses 1B and 14, selected as representative serotypes for viral groups B and A of human rhinoviruses, respectively. In comparison with results previously obtained, the introduction of the fluorine atom seems to exert a positive influence on the activity against serotype 14 while counteracting the effect against serotype 1B.

An Overview of 2‐Styrylchromones: Natural Occurrence, Synthesis, Reactivity and Biological Properties

“…A variety of biological properties have been ascribed to 2-SCs, including antiallergic, [112] anti-inflammatory, [113] antioxidant, [114][115][116][117][118] antitumor [10][11][12]36,39,119] and antiviral, [49,58,66] as well as affinity and selectivity for A 3 adenosine receptors, [38] reviewed by Gomes et al in 2010. [120] Here we update the biological assessment of 2-SCs, but also describe some studies not considered in that review.…”

“…The reaction is usually carried out in the presence of an aqueous solution of sodium hydroxide in ethanol [25,[41][42][43] or methanol [44,45] but the use of barium hydroxide in ethanol [46][47][48] or methanol [49] and LiHMDS [lithium bis(trimethylsilyl)amide] in THF [50] has also been reported (Scheme 5). These 2′-hydroxycinnamylideneacetophenones 24 undergo cyclodehydrogenation to give the corresponding 2-SCs (E)-25 in the presence either of a catalytic amount of iodine in DMSO [41,42,[44][45][46][47][51][52][53][54] or of SeO 2 in pentanol or xylenes.…”

“…of the halogen led to a mixture of C-6 or C-8 monohalogenated 5-hydroxy-2-styrylchromones 30 (Scheme 6). [54] Other methodologies for preparing 3-hydroxy-2-styrylchromones 26 have also been developed, with 2′-hydroxycinnamylideneacetophenones 23 being treated with hydrogen peroxide in alkaline medium [43,49,50,[55][56][57][58] or diethylamine in a 2:1 mixture of DMSO/1,4-dioxane [47] (Scheme 5). In these cases pyranone ring closure occurs through an Algar-Flynn-Oyamada Scheme 5.…”

“…[80] A similar procedure used cinnamoyl chlorides in potassium carbonate/acetone medium, and cyclodehydration occurred in the presence of concentrated sulfuric acid in ethanol at reflux (Scheme 11). [49,81] The synthesis of 3-cinnamoyl-5-hydroxy-2-styrylchromones 40 was achieved through a two-step procedure involving the condensation of 2′,6′-dihydroxyacetophenone with 2 equiv. of appropriate cinnamic acids in the presence of DCC and 4-PPy in dichloromethane at room temperature to afford the 2′,6′-dicinnamoyloxyacetophenones 39, which underwent cyclodehydration on treatment with potassium carbonate in dry pyridine at 120°C [13,82] or under MW irradiation [83] (Scheme 12).…”

Synthesis and Transformation of Halochromones

“…Oxidative cyclization of 5'-fluoro-2'-hydroxychalcone 34 (R = phenyl) and 5'-fluoro-2'-hydroxycinnamylideneacetophenone 34 (R = styryl) to the corresponding 6-fluoro-3-hydroxyflavone 35 (R = phenyl) and 6-fluoro-3-hydroxy-2-styrylchromone 35 (R = styryl), respectively, can be achieved by reaction with alkaline hydrogen peroxide (Scheme 12) [84]. Similar reaction conditions have been successfully used for the synthesis of other mono-and poly-halochromones [85][86][87][88][89].…”