Grandisines C−G, Indolizidine Alkaloids from the Australian Rainforest Tree Elaeocarpus grandis

Five new indolizidine alkaloids, grandisines C, D, E, F, and G (4−8), and one known indolizidine alkaloid, (−)-isoelaeocarpiline (3), were isolated from the leaves of Elaeocarpus grandis and their structures determined by 1D and 2D NMR spectroscopy. Grandisine C (4) is isomeric with the known compound rudrakine (1). The absolute configuration of grandisine D (5) was deduced by its conversion to (−)-isoelaeocarpiline. Grandisine E (6) contains a novel tetracyclic ring system. Grandisine F (7) is the 14-amino analogue of grandisine C. Grandisine G (8) contains the novel combination of a piperidine attached to an indolizidine. Grandisines C, D, F, and G and (−)-isoelaeocarpiline showed receptor binding affinity for the human δ-opioid receptor with IC50 values of 14.6, 1.65, 1.55, 75.4, and 9.9 μM, respectively.