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

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

Cytotoxic and Noncytotoxic Metabolites from <i>Teratosphaeria</i> sp. FL2137, a Fungus Associated with <i>Pinus clausa</i>

A new naphthoquinone, teratosphaerone A (<b>1</b>), four new naphthalenones, namely, teratosphaerone B (<b>2</b>), structurally related to <b>1</b>, iso-balticol B (<b>3</b>), iso-balticol B-4,9-acetonide (<b>4</b>), and (+)-balticol C (<b>5</b>), a new furanonaphthalenone, (3a<i>S</i>,9<i>R</i>,9a<i>S</i>)-1­(9a),3­(3a),9-hexahydromono­sporascone (<b>6</b>), and the known metabolite monosporascone (<b>7</b>) were isolated from <i>Teratosphaeria</i> sp. FL2137, a fungal strain inhabiting the internal tissue of recently dead but undecomposed foliage of <i>Pinus clausa</i>. The structures of <b>1</b>–<b>6</b> were elucidated on the basis of their spectroscopic data including 2D NMR, and absolute configurations of <b>2</b>, <b>3</b>, and <b>6</b> were determined by the modified Mosher’s ester method. When evaluated in a panel of five tumor cell lines, metabolites <b>1</b> and <b>7</b> isolated from a cytotoxic fraction of the extract exhibited moderate selectivity for metastatic breast adenocarcinoma cell line MDA-MB-231. Of these, <b>1</b> showed cytotoxicity to this cell line with an IC₅₀ of 1.2 ± 0.1 μM

Delitschiapyrone A, a Pyrone–Naphthalenone Adduct Bearing a New Pentacyclic Ring System from the Leaf-Associated Fungus <i>Delitschia</i> sp. FL1581

Delitschiapyrone A (<b>1</b>), an α-pyrone–naphthalenone adduct with an unprecedented pentacyclic ring system, was isolated from a solid culture of the leaf-associated fungus <i>Delitschia</i> sp. FL1581. The structure of <b>1</b> was elucidated by spectroscopic analysis and X-ray crystallography, and its absolute configuration was defined by experimental and calculated ECD. Biosynthetically, the unique 6/6/5/7/6 pentacyclic core of <b>1</b> may be formed by an intermolecular Diels–Alder-type addition of the precursors derived from (1′<i>R</i>)-2′,3′-dihydropyrenocine C (<b>2</b>) and 6-ethyl-2,7-dimethoxyjuglone (<b>3</b>) found to co-occur with <b>1</b> in this fungus

Geopyxins A–E, <i>ent</i>-Kaurane Diterpenoids from Endolichenic Fungal Strains <i>Geopyxis</i> aff. <i>majalis</i> and <i>Geopyxis</i> sp. AZ0066: Structure–Activity Relationships of Geopyxins and Their Analogues

Four new <i>ent</i>-kaurane diterpenoids, geopyxins A–D (<b>1</b>–<b>4</b>), were isolated from <i>Geopyxis</i> aff. <i>majalis</i>, a fungus occurring in the lichen <i>Pseudevernia intensa</i>, whereas <i>Geopyxis</i> sp. AZ0066 inhabiting the same host afforded two new <i>ent</i>-kaurane diterpenoids, geopyxins E and F (<b>5</b> and <b>6</b>), together with <b>1</b> and <b>3</b>. The structures of <b>1</b>–<b>6</b> were established on the basis of their spectroscopic data, while the absolute configurations were assigned using modified Mosher’s ester method. Methylation of <b>1</b>–<b>3</b>, <b>5</b>, and <b>6</b> gave their corresponding methyl esters <b>7</b>–<b>11</b>. On acetylation, <b>1</b> and <b>7</b> yielded their corresponding monoacetates <b>12</b> and <b>14</b> and diacetates <b>13</b> and <b>15</b>. All compounds were evaluated for their cytotoxic and heat-shock induction activities. Compounds <b>2</b>, <b>7</b>–<b>10</b>, <b>12</b>, <b>14</b>, and <b>15</b> showed cytotoxic activity in the low micromolar range against all five cancer cell lines tested, but only compounds <b>7</b>–<b>9</b>, <b>14</b>, and <b>15</b> were found to activate the heat-shock response at similar concentrations. From a preliminary structure–activity perspective, the electrophilic α,β-unsaturated ketone carbonyl motif present in all compounds except <b>6</b> and <b>11</b> was found to be necessary but not sufficient for both cytotoxicity and heat-shock activation