An efficient procedure for the preparation of natural products bearing the 2-(2-phenylethyl)chromone skeleton

Abstract

Several 2-(2-phenylethyl)chromones have been shown to possess neuroprotective activity. However, limited synthetic methods have been disclosed to construct the 2-(2-phenylethyl)chromone skeleton. Herein we report a straightforward 3-step preparation of five naturally occurring 2-(2-phenylethyl)chromones utilizing the Claisen condensation as the key step.

5-Hydroxy-2-(2-phenylethyl)chromone (5-HPEC): A novel non-nitrogenous ligand for 5-HT2B receptor

“…We recently developed an efficient method to synthesize 5-HPEC. 19 Here we report our further characterization on this interesting natural product against a number of CNS receptors in order to identify the potential molecular targets that may be related to its biological activity.…”

Soft-enolization Baker–Venkataraman Rearrangement Enabled Total Synthesis of Dirchromones and Related 2-Substituted Chromones

“…2 As for the second group, several of the large number of 2-phenylethylchromones 3 found in agarwood, the fungiinfected wood of several Thymelaeaceae, 3 were reported to exhibit interesting in vitro anti-inflammatory properties. 4,5 Among the reported synthetic approaches toward these biologically active 2-substituted chromones, including the ubiquitous flavone scaffold 4, the Claisen condensation of activated cinnamates onto 2′-hydroxyacetophenone 6 is the most common route. More specifically, its intramolecular counterpart, i.e., the Baker−Venkataraman (B−V) rearrangement of cinnamoyl ester of 2′-hydroxyacetophenone, widely used.…”

“…Among the reported synthetic approaches toward these biologically active 2-substituted chromones, including the ubiquitous flavone scaffold 4 , the Claisen condensation of activated cinnamates onto 2′-hydroxyacetophenone is the most common route. More specifically, its intramolecular counterpart, i.e., the Baker–Venkataraman (B–V) rearrangement of cinnamoyl ester of 2′-hydroxyacetophenone, , is widely used.…”

“…The preparation of ( S )-deoxydirchromone 15a was the main focus of the initial investigation, provided that it could then be readily oxidized to racemic sulfoxide 1 using 3-chloroperbenzoic acid ( m -CPBA) . The first explored strategy was modeled based on classical syntheses of 2-substituted chromones through a Claisen condensation , of methyl 3-methylthiopropionate 5 and 2′-hydroxyacetophenone 9a (Scheme , route A). This would have been followed by acidic dehydrative cyclization to compound 14 and oxidation to generate vinylsulfide 15a .…”

Synthesis and Characterization of 5-Hydroxy-2-(2-phenylethyl)chromone (5-HPEC) and Its Analogues as Non-nitrogenous 5-HT2B Ligands

“…34 Accordingly, the same strategy was employed in the synthesis of the proposed analogues (Scheme 2). The appropriate acetophenone (20) was protected with MOM as previously described to give 21.…”