<i>neo-</i>Clerodane Diterpenoids from <i>Ajuga bracteosa</i>

Abstract

Different <i>neo</i>-clerodane diterpenoids were isolated from a dichloromethane extract of <i>Ajuga bracteosa</i> depending on the isolation procedure used, owing to the labile nature of these tetrahydrofurofuran derivatives. Under “hydroxyl-free” purification conditions, both clerodin- and dihydroclerodin-type diterpenes were obtained [four new compounds, ajubractins A–D (<b>1</b>–<b>4</b>), along with clerodin (<b>5</b>), 3-<i>epi</i>-caryoptin (<b>6</b>), ajugapitin (<b>7</b>), 14,15-dihydroclerodin (<b>8</b>), 3-<i>epi</i>-14,15-dihydrocaryoptin (<b>9</b>), ivain II (<b>10</b>), and 14,15-dihydroajugapitin (<b>11</b>)]. When methanol–water mixtures were used for a C₁₈ reversed-phase prepurification procedure and for semipreparative HPLC, the new ajubractin E (<b>12</b>) was also isolated along with <b>3</b> and <b>8</b>–<b>11</b>, as previously, but <b>7</b> was the only tetrahydrofurofuran derivative obtained. Epimeric (15<i>R</i> and 15<i>S</i>) mixtures were obtained instead of 14-hydro-15-hydroxyclerodin derivatives [15-hydroxyajubractin C (<b>13</b>), 14-hydro-15-hydroxyajugachin A (<b>14</b>), and 14-hydro-15-hydroxyajugapitin (<b>15</b>)], along with 15-<i>epi</i>-lupulin B (<b>16</b>). The structures of the new compounds were elucidated by NMR and MS data analysis and by comparison with values previously reported. Antifeedant activity against <i>Spodoptera littoralis</i> larvae was evaluated for the compounds obtained.