Chirality Determination and Anti-inflammatory Activity of Phthalide Monomers in Angelica sinensis

Angelica sinensis, commonly known as Dang-gui, is a renowned medicinal and edible plant. Phthalide monomers are the key bioactive components in A. sinensis, yet their optical purities and absolute configurations remain unclear. In this study, three new phthalide monomers (1-3) and 10 known ones (4-13) were isolated from A. sinensis; their chiral resolutions, absolute configurations, and anti-inflammatory activities were systematically elucidated. Our study summarizes the optical purity characteristics of phthalide monomer derivatives in Dang-gui, revealing that the optical purity of the derivatives is significantly influenced by the position of their chiral centers. When the chiral center is located at the six-membered ring or the n-butyl chain, the derivatization reaction exhibits no chiral selectivity, yielding racemates. In contrast, when the chiral center is at C-8 on the five-membered ring, the derivatization reaction shows significant chiral selectivity, favoring the formation of scalemic mixtures dominated by the S-configuration. This study provides critical insights for defining the stereochemistry of phthalides in A. sinensis and related species.