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

Abstract

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