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 represented the first examples of trimeric Gelsemium alkaloids that featuring 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.