Challenges in chiral discrimination at the H-2 and H-10 positions of dihydrobenzofuran from Artemisiacapillaris.

A phytochemical investigation into the low-polarity fraction of Artemisia capillaris facilitated the isolation of twenty-two natural compounds. These compounds, termed Artemicapillasin O-X (1a/1b-4a/4b, 5a, 6a/6b-8a/8b, 9a, 10b, 11b, 12a, and 12b), were identified as previously undescribed 2,3-dihydrobenzofuran (2,3-DHB) derivatives. Their structures were elucidated using NMR analysis, which included coupling constant analysis, chiroptical characterization (electronic circular dichroism [ECD] and optical rotatory dispersion [ORD]), computational approaches (DP4+ probability analysis and dJ/iJ-DP4 protocol), and X-ray diffraction. Subsequent analyses identified that for 2,3-DHB derivatives featuring only two chiral centers at C-2 and C-10, the determination of absolute configuration relies on coupling constants, Cotton effects in CD spectra, and ORD measurements. A novel rule, termed Chen's Rule, was established to facilitate rapid discrimination of stereochemical relationships between H-2 and H-10 in 2,3-DHB derivatives. This rule prompted structural revisions of similar compounds reported in the prior literature. Furthermore, all compounds were assayed at a concentration of 100 μM for their inhibitory activity against xanthine oxidase (XOD) in vitro, where compounds 7a and 7b displayed moderate effects, whereas the others demonstrated negligible activity.