Chirality Determination and Anti-inflammatory Activity of Phthalide Monomers in <i>Angelica sinensis</i>

<i>Angelica sinensis</i>, commonly known as Dang-gui, is a renowned medicinal and edible plant. Phthalide monomers are the key bioactive components in <i>A. sinensis</i>, yet their optical purities and absolute configurations remain unclear. In this study, three new phthalide monomers (<b>1</b>-<b>3</b>) and 10 known ones (<b>4</b>-<b>13</b>) were isolated from <i>A. sinensis</i>; 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 <i>n</i>-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 <i>S</i>-configuration. This study provides critical insights for defining the stereochemistry of phthalides in <i>A. sinensis</i> and related species.