Alstotriamine A, a triamino monoterpene indole alkaloid with an unprecedented pentacyclic caged skeleton and anti-inflammatory alkaloids from Alstonia mairei.

A novel triamino monoterpene indole alkaloid, alstotriamine A (1), a new monoterpene indole alkaloid (2), and five known analogues (3-7) were isolated from the branches and leaves of Alstonia mairei. Their structures were elucidated via extensive spectroscopic methods and quantum chemical calculations including the 13C NMR-DP4+ analysis and electronic circular dichroism (ECD) calculations. Alstotriamine A (1), possessing an unprecedented pentacyclic caged skeleton incorporating with a third nitrogen atom, represents the first example of C-3 and C-17 cyclic corynanthe alkaloid, and a plausible biosynthetic pathway was proposed. Furthermore, compounds 1, 2, 5, and 7 displayed significant inhibitory effects on the LPS-induced NO production in RAW264.7 mouse macrophages with IC50 values ranging from 4.6 to 16.2 μM, and the active compounds 2 and 5 dose-dependently decreased the levels of the pro-inflammatory cytokines TNF-α and IL-6.