Isolation, Absolute Configuration, and Biological Activities of Chebulic Acid and Brevifolincarboxylic Acid Derivatives from <i>Euphorbia hirta</i>

Twenty new chebulic acid and brevifolincarboxylic acid derivatives, including eight optically pure or achiral compounds (<b>1</b>–<b>7</b> and <b>14</b>) and six pairs of enantiomers (<b>8a</b>/<b>8b</b>–<b>13a</b>/<b>13b</b>), along with nine known analogues (<b>15</b>–<b>23</b>), were isolated from an EtOH extract of the aerial parts of <i>Euphorbia hirta</i>. The absolute configurations of the new compounds were assigned based on single-crystal X-ray diffraction analysis and comparison of the experimental and calculated ECD data. Racemic or scalemic mixtures of <b>8</b>–<b>13</b> were isolated, and their enantiomers were analyzed by chiral-phase HPLC-ECD measurements. Compound <b>12</b> possesses an unprecedented 2<i>H</i>-cyclopenta­[<i>de</i>]­chromene-2,5­(4<i>H</i>)-dione scaffold. Compounds <b>12</b>, <b>20</b>, and <b>23</b> displayed moderate inhibitory effects against lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, while all the isolates exhibited significant DPPH radical scavenging activities with EC₅₀ values of 2.2–15.8 μM.