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

Artemverlotolides A (1) and B (2), two unprecedented sesquiterpenes possessing a 10-oxa-tetracyclo[3.3.2.1.1.04,10.07,8]tridecane scaffold for 1 and an 11-oxa-tetracyclo[3.3.3.1.04,10.04,11.07,8]tetradecane backbone for 2, were isolated from Artemisia verlotorum 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 1 and 2 was achieved using isoalantolactone (14) as the starting material under the Suárez conditions and intramolecular Giese radical addition as the key steps. Additionally, compound 2 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.