Gelstriamine A, a Triamino Monoterpene Indole Alkaloid with a Caged 6/5/7/6/6/5 Scaffold and Analgesic Alkaloids from <i>Gelsemium elegans</i> Stems

Abstract

A novel triamino monoterpene indole alkaloid with an unprecedented skeleton, gelstriamine A (<b>1</b>), four new monoterpene indole alkaloids (<b>2</b>-<b>5</b>), and 12 known analogues (<b>6</b>-<b>17</b>) were isolated from <i>Gelsemium elegans</i>. The structures of <b>1</b>-<b>5</b> were established using extensive spectroscopic techniques, NMR calculations with i<i>J</i>/d<i>J</i>-DP4 and 2D C-H COSY ANNs analysis, ECD calculations, chemical methods, and single crystal X-ray diffraction analysis. Gelstriamine A (<b>1</b>) possesses an unprecedented 6/5/7/6/6/5 heterohexacyclic scaffold bearing a unique hexahydrooxazolo[4,5-<i>b</i>]pyridin-2(3<i>H</i>)-one motif, and a plausible biosynthetic pathway was proposed. All the isolated alkaloids <b>1</b>-<b>17</b> showed discernible analgesic activities in an acetic acid-induced writhing test in mice, and <i>N</i>-desmethoxyhumantenine <i>N</i>₄-oxide (<b>3</b>) exhibited more potent analgesic activities than those of morphine at doses of 0.04 and 0.2 mg/kg.