Structurally Diverse Indole Alkaloids with Vasorelaxant Activity from Melodinus hemsleyanus.

Six new structurally diverse indole alkaloids, melohemsines J-M (1-4), 11-hydroxy-Δ14-vincamine (5), and 11-hydroxy-16-epi-Δ14-vincamine (6), and 15 known alkaloids were isolated from the leaves and twigs of Melodinus hemsleyanus Diels. These new compounds and their absolute configurations were determined through spectroscopic data analyses, X-ray diffraction, and computational methods. Melohemsine J (1) is the first example of a melodinus-type alkaloid possessing a 6/6/5/5/6/5 hexacyclic skeleton and containing a tetrahydrofuro[2,3-b]pyridine-2(3H)-one unit. Melohemsine K (2) is an unusual aspidosperma-type alkaloid possessing a 6/5/6/5/5 pentacyclic architecture with a contracted E ring (loss of CH2). Compounds 5-10 and 16 exhibited vasorelaxant activities with EC50 values of 0.8-3.8 μM. In addition, compound 4 displayed moderate cytotoxicity toward the tumor cell lines HepG2 and A-549 with EC50 values of 18.7 and 28.7 μM, respectively.