Isolation and structural characterization of dihydrobenzofuran congeners of licochalcone A

In an effort to explore the residual complexity of naturally occurring chalcones from the roots of Glycyrrhiza inflata (Fabaceae), two new licochalcone A (LicA) derivatives were isolated as trace metabolites from enriched fractions. Both constituents contain a dihydrofuran moiety linked to carbons C-4 and C-5 of the retrochalcone core. Compound 1 (LicAF1) represents a new chemical entity, whereas compound 2 (LicAF2) has previously been reported as a Lewis acid catalyzed rearrangement of LicA. Evaluation of chirality revealed that both dihydrofuran derivatives existed as a mixture of R and S enantiomers. Interestingly, when solutions were exposed to sunlight, both dihydrofuran retrochalcones, initially isolated as trans isomers, were found to rapidly isomerize yielding trans and cis isomers. Analysis of the 1D ¹H NMR spectra of the photolysis products revealed the presence of two sets of proton resonances ascribed to each of the geometric isomers. An up-field shift of all proton resonances arising from the cis isomer was observed, suggesting that anisotropic shielding effects were introduced through an overall perturbation of the 3-dimensional structure upon photoisomerization. Similar up-field shifts were observed in the ¹³C spectrum of the cis isomer, except for the CO, C-α, and C-6 carbons, which experienced downfield shifts. Analogous NMR results were observed for LicA. Hence, the results presented herein encompass the isolation and full characterization of LicAF analogs 1 and 2, and observations of their trans-to-cis photoisomerization through the systematic analysis of their NMR spectra.