Bullatin and bullanin: two novel, highly cytotoxic acetogenins from Asimina triloba

Two new highly cytotoxic adjacent bis-tetrahydrofuran acetogenins, bul- latin (2) (10-hydroxy-4-deoxybullatacin) and bullanin (5) (30-hydroxy- 4-deoxybullatacin), have been isolated from the ethanolic extract of the stem bark of Asimina triloba by directing the fractionation with brine shrimp lethality. In addition to these two new compounds, two previously reported acetogenins, squamocin (3) (28-hydroxy-4-deoxybullatacin) and motrilin (4) (29-hydroxy-4-deoxybullatacin) which are new to this spe- cies, were obtained. Through spectral analysis these four acetogenins were structurally identified as hydroxylation isomers of bullatacin (1) which was recently patented as an antitumor agent. All of these aceto- genins showed high potencies in the brine shrimp test (BST) and in cy- totoxicity tests against human solid tumor cell lines in culture, with certain potencies quite comparable to those of bullatacin (1) and seve- ral orders of magnitude greater than those of adriamycin