Antineoplastic Agents. 595. Structural Modifications of Betulin and the X‑ray Crystal Structure of an Unusual Betulin Amine Dimer

The lupane-type triterpene betulin (<b>1</b>) has been subjected to a series of structural modifications for the purpose of evaluating resultant cancer cell growth inhibitory activity. The reaction sequence <b>7</b> → <b>11</b> → <b>12</b> was especially noteworthy in providing a betulin-derived amine dimer. Other unexpected synthetic results included the <b>11</b> and <b>13</b>/<b>14</b> → <b>17</b> conversions, which yielded an imidazo derivative. X-ray crystal structures of dimer <b>12</b> and intermediate <b>25</b> are reported. All of the betulin modifications were examined for anticancer activity against the P388 murine and human cell lines. Significant cancer cell growth inhibition was found for <b>4</b>, <b>8</b>, <b>9</b>, <b>15</b>/<b>16</b>, <b>19</b>, <b>20</b>, <b>24</b>, and <b>26</b>, which further defines the utility of the betulin scaffold

Antineoplastic Agents. 587. Isolation and Structure of 3-Epipancratistatin from <i>Narcissus</i> cv. Ice Follies

Bioassay-guided (cancer cell line) separation of an extract prepared from <i>Narcissus</i> cv. Ice Follies (from The Netherlands) led to the isolation of a new Amaryllidaceae isocarbostiryl, 3-epipancratistatin (<b>1b</b>), as well as narciclasine (<b>2</b>). This <i>Narcissus</i> cultivar was found to be a good source of narciclasine. The structure of <b>1b</b> was established by high-resolution mass and high-field 2D NMR spectroscopic analyses. Against a panel of murine and human cancer cell lines, 3-epipancratistatin (<b>1b</b>) led to cell growth inhibition (GI₅₀ 2.2–0.69 μg/mL) some 100× less than that found for pancratistatin (<b>1a</b>) and narciclasine (<b>2</b>), thereby revealing an important configurational requirement in <b>1a</b> for strong cancer cell growth inhibition

Antineoplastic Agents. 587. Isolation and Structure of 3-Epipancratistatin from <i>Narcissus</i> cv. Ice Follies

Bioassay-guided (cancer cell line) separation of an extract prepared from <i>Narcissus</i> cv. Ice Follies (from The Netherlands) led to the isolation of a new Amaryllidaceae isocarbostiryl, 3-epipancratistatin (<b>1b</b>), as well as narciclasine (<b>2</b>). This <i>Narcissus</i> cultivar was found to be a good source of narciclasine. The structure of <b>1b</b> was established by high-resolution mass and high-field 2D NMR spectroscopic analyses. Against a panel of murine and human cancer cell lines, 3-epipancratistatin (<b>1b</b>) led to cell growth inhibition (GI₅₀ 2.2–0.69 μg/mL) some 100× less than that found for pancratistatin (<b>1a</b>) and narciclasine (<b>2</b>), thereby revealing an important configurational requirement in <b>1a</b> for strong cancer cell growth inhibition