Synthesis and Transformation of 5-Acetyl-2-aryl-6-hydroxybenzofurans into Furanoflavanone Derivatives

Abstract

Tandem palladium-catalyzed Sonogashira cross-coupling and heteroannulation of 3-bromo-2,4-dihydroxy-5-iodoacetophenone with arylacetylenes followed by the base-mediated Claisen–Schmidt aldol condensation of the intermediate 5-acetyl-2-aryl-7-bromo-6-hydroxybenzofurans with benzaldehyde derivatives afforded the corresponding linear 2-arylbenzofuranchalcone hybrids. The presence of the o-hydroxy-trans-α,β-unsaturated carbonyl moiety in the prepared furanochalcone hybrids facilitated acid-mediated cycloisomerization into the corresponding linear furanoflavanones. The structures of the prepared compounds were confirmed using a combination of spectrometric techniques complemented with single crystal XRD analysis.

In Vitro Evaluation and Docking Studies of 5-oxo-5H-furo[3,2-g]chromene-6-carbaldehyde Derivatives as Potential Anti-Alzheimer’s Agents

“…Its 13 C-NMR spectrum, on the other hand, revealed the presence of increased number of carbon signals in the aromatic region and the additional carbonyl signal at δ 189.2 ppm corresponding to the formyl group. The o -iodophenolic moiety has previously been found to undergo tandem palladium catalyzed Sonogashira cross-coupling and heteroannulation with terminal acetylenes to afford benzofuran derivatives [24]. Next we exploited this strategy on 1 with various terminal acetylenes in the presence of dichlorobis(triphenyl)phosphine(II) as a source of active Pd(0) species and CuI as co-catalyst using potassium carbonate as a base in aqueous dimethyl formamide (DMF) at RT for 3 h. Aqueous work-up and purification by silica gel column chromatography afforded the corresponding 2-aryl-5-oxo-5 H -furo[3,2- g ]chromene-6-carbaldehydes 2a – i (see Table 1 for the designation of substituent R).…”

Synthesis, In Vitro Evaluation and Molecular Docking of the 5-Acetyl-2-aryl-6-hydroxybenzo[b]furans against Multiple Targets Linked to Type 2 Diabetes

“…The high-resolution mass spectra were recorded at the University of Stellenbosch using a Waters Synapt G2 Quadrupole Time-of-flight mass spectrometer (Waters Corp., Milford, MA, USA) at an ionization potential of 70 eV. The synthesis and analytical data for 2,4-dihydroxy-5-iodoacetophenone, were reported in our previous investigation [23].…”

“…The above-mentioned compounds were accessible via tandem Sonogashira cross-coupling and Cacchi-type heteroannulation of the known 2,4-dihydroxy-5-iodoacetophenone (1) [23].…”

“…The above-mentioned compounds were accessible via tandem Sonogashira cross-coupling and Cacchi-type heteroannulation of the known 2,4-dihydroxy-5-iodoacetophenone (1) [23]. The latter was subjected to phenylacetylene derivatives in the presence of dichlorobis(triphenylphosphine)palladium(II)-copper iodide catalyst mixture, triphenylphosphine as ligand and potassium carbonate as a base in aqueous dimethylformamide at 70 °C (Scheme 1).…”

Crystal structure of 1-(6-hydroxy-2-phenylbenzofuran-5-yl)ethan-1-one, C16H12O3

“…We have previously prepared a series of ortho-hydroxyacetyl substituted 2-arylbenzofurans and evaluated these compounds through enzymatic assays in vitro for inhibitory effect against α-glucosidase, PTP1B, β-secretase and cyclooxygenase-2, as well as for free radical scavenging potential [5]. The presence of the acetyl group, on the other hand, has been found to facilitate Claisen-Schmidt aldol condensation with benzaldehyde derivatives followed by cycloisomerization of the intermediate ortho-hydroxychalcones into furoflavonoids [13,14]. We have also employed the orthohydroxyacetyl substituted 2-arylbenzofurans as precursors for the synthesis of ortho-acetoxy substituted benzofuran-1,2,3-selenadiazoles and evaluated these molecular hybrids for α-glucosidase inhibitory activity, anti-inflammatory and antioxidant properties [15].…”