Oligomeric monoterpenoid indole alkaloids from the flowers of Gelsemium elegans with anti-inflammatory and anti-fibrotic activities

Abstract

Gelsepolycines A–F (1–6), six oligomeric monoterpenoid indole alkaloids with new skeletons, together with their biosynthetic precursors (7–8), were isolated from the flowers of Gelsemium elegans. Compounds 1 and 4–6 represent the first examples of trimeric Gelsemium alkaloids that feature complex sterically compact frameworks with 17–19 chiral centers. Furthermore, these compounds were constructed through unprecedented C₁₄–C₁₉ and C₁₄–N₄ linkages. Interestingly, all these oligomeric alkaloids (1–6) could be derived from the same monomer precursor 7 in the proposed biogenetic pathway. The anti-inflammatory and anti-fibrotic activities of these isolates were evaluated, and compound 3 demonstrated potent effects in vitro and in vivo. The biomimetic synthesis of 3 was achieved according to the proposed biogenetic pathway.