Anteaglonialides A–F and Palmarumycins CE₁–CE₃ from <i>Anteaglonium</i> sp. FL0768, a Fungal Endophyte of the Spikemoss <i>Selaginella arenicola</i>

Abstract

Anteaglonialides A–F (<b>1</b>–<b>6</b>), bearing a spiro­[6-(tetrahydro-7-furanyl)­cyclohexane-1,2′-naphtho­[1,8-<i>de</i>]­[1,3]-dioxin]-10-one skeleton, three new spirobisnaphthalenes, palmarumycins CE₁–CE₃ (<b>7</b>–<b>9</b>), nine known palmarumycin analogues, palmarumycins CP₅ (<b>10</b>), CP_4a (<b>11</b>), CP₃ (<b>12</b>), CP₁₇ (<b>13</b>), CP₂ (<b>14</b>), and CP₁ (<b>15</b>), CJ-12,371 (<b>16</b>), 4-<i>O</i>-methyl CJ-12,371 (<b>17</b>), and CP₄ (<b>18</b>), together with a possible artifact, 4a(5)-anhydropalmarumycin CE₂ (<b>8a</b>), and four known metabolites, <i>O</i>-methylherbarin (<b>19</b>), herbarin (<b>20</b>), herbaridine B (<b>21</b>), and hyalopyrone (<b>22</b>), were encountered in a cytotoxic extract of a potato dextrose agar culture of <i>Anteaglonium</i> sp. FL0768, an endophytic fungus of the sand spikemoss, <i>Selaginella arenicola.</i> The planar structures and relative configurations of the new metabolites <b>1</b>–<b>9</b> were elucidated by analysis of extensive spectroscopic data, and the absolute configuration of <b>1</b> was determined by the modified Mosher’s ester method. Application of the modified Mosher’s ester method combined with the NOESY data resulted in revision of the absolute configuration previously proposed for <b>10</b>. Co-occurrence of <b>1</b>–<b>6</b> and <b>7</b>–<b>18</b> in this fungus led to the proposal that the anteagloniolides may be biogenetically derived from palmarumycins. Among the metabolites encountered, anteaglonialide F (<b>6</b>) and known palmarumycins CP₃ (<b>12</b>) and CP₁ (<b>15</b>) exhibited strong cytotoxic activity against the human Ewing’s sarcoma cell line CHP-100, with IC₅₀ values of 1.4, 0.5, and 1.6 μM, respectively