Alkaloids from Alangium javanicum and Alangium grisolleoides that mediate Cu²⁺-dependent DNA strand scission

Crude CH₂Cl₂-MeOH extracts prepared from Alangium javanicum and A. grisolleoides were found to induce DNA strand breakage in the presence of Cu²⁺ and were subjected to bioassay-guided fractionation to permit identification of the active principle(s). Javaniside (1), a novel alkaloid possessing an unusual monoterpenoid oxindole skeleton, was identified as an active principle contributing to the DNA cleavage activity observed for the crude extract of A. javanicum. Alangiside (2), a tetrahydroisoquinoline monoterpene glucoside widely distributed in the genus Alangium, was also isolated from A. grisolleoides as a new type of Cu²⁺-dependent DNA cleavage agent. The relative configuration of the asymmetric centers in javaniside was established by analysis of ¹H-¹H coupling constants and NOESY correlations. Semisynthesis of javaniside from secologanin (3) established the absolute stereochemistry of javaniside.