Two novel iboga alkaloids with neuroprotective effects from Tabernaemontana corymbosa

Two novel members of the iboga-alkaloid, tabcorymines A and B, were isolated from the stem bark of Tabernaemontana corymbosa. Tabcorymine A (1) features a unique diaza [5.5.6.6] fenestrane structure with six chiral centers, while tabcorymine B (2) possesses an indole-oxabicyclo[5.2.1] decane skeleton. We elucidated their structures and absolute configurations using extensive spectroscopy, the ACD/structure elucidator (ACD/SE), quantum chemical calculations, and DP4+ probability analyses. The C-19 chiral hydroxyl groups of both compounds were determined through CD data from the in situ formed [Rh2(OCOCF3)4] complex and Mosher's method, respectively. Furthermore, we have shown that tabcorymine A (1) inhibits MPTP-induced SH-SY5Y cell injury. Western blot and molecular docking experiments demonstrated that tabcorymine A (1) reduces the expression of the Bax protein, thereby inhibiting neuronal apoptosis and providing neuronal protection.