Artemverlotolides A and B, Two Sesquiterpenes from <i>Artemisia verlotorum</i> Lamotte: Structural Elucidation, Bioinspired Synthesis, and Antineuroinflammatory Activity

Artemverlotolides A (<b>1</b>) and B (<b>2</b>), two unprecedented sesquiterpenes possessing a 10-oxa-tetracyclo[3.3.2.1.1.0^4,10.0^7,8]tridecane scaffold for <b>1</b> and an 11-oxa-tetracyclo[3.3.3.1.0^4,10.0^4,11.0^7,8]tetradecane backbone for <b>2</b>, were isolated from <i>Artemisia verlotorum</i> Lamotte. Their structures were elucidated by a comprehensive analysis of HRESIMS data, 1D and 2D NMR, IR, and single-crystal X-ray diffraction experiments. A biomimetic synthesis of compounds <b>1</b> and <b>2</b> was achieved using isoalantolactone (<b>14</b>) as the starting material under the Suárez conditions and intramolecular Giese radical addition as the key steps. Additionally, compound <b>2</b> exhibited antineuroinflammatory activity by alleviating the effects of overproduction of NO and overexpression of proinflammatory genes and cytokines in LPS-stimulated BV-2 microglial cells, which might be mediated through downregulation of STAT1 phosphorylation.