MURICATETROCINS-A AND MURICATETROCINS-B AND GIGANTETROCIN-B - 3 NEW CYTOTOXIC MONOTETRAHYDROFURAN-RING ACETOGENINS FROM ANNONA-MURICATA

Extracts from the seeds of Annona muricata yielded three new Annonaceous acetogenins: muricatetrocin A ( = (5S)-3-{(2R)-2-hydroxy-9-{(2R,5S)-tetrahydro-5-[(1S,4S,5S)-1,4,5-trihydroxyheptadecyl]furan-2-yl}nonyl}-5-methylfuran-2(5H)-one; 1), muricatetrocin B ( = (5S)-{(2R)-2-hydroxy-9-{(2S,5S)-tetrahydro-5-[(1S,4S,5S)-1,4,5-trihydroxyheptadecyl]furan-2-yl}nonyl}-5-methylfuran-2(5H)-one; 2), and gigantetrocin B ( = (5S)-3-{(2R)-2-hydroxy-7-{(2S, 5S)-tetrahydro-5-[(1S,4R, 5R)-1,4,5-trihydroxynonadecyl]furan-2-yl}heptyl}-5-methyl-furan-2(5H)-one; 3). Their C-skeletons were deduced by mass spectrometry. Configurations were determined by H-1-NMR of ketal derivatives and 2D-NMR experiments utilizing Mosher esters. A previously described compound, gigantetrocin A ( = (5S)-3-{(2R)-2-hydroxy-7-{(2S,5S)-tetrahydro-5-[(1S,4S,5S)-1,4,5-trihydroxynona-decyl]furan-2-yl}heptyl}-5-methylfuran-2-(5H)one; 4), was also isolated and is new to this species. Compounds 1-4 were all selectively cytotoxic for the HT-29 human colon-tumor cell line with potencies at least 10 times that of adriamycin.