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 delta-opioid receptor with IC50 values of 14.6, 1.65, 1.55, 75.4, and 9.9 mu M, respectively.