GONIONENIN - A NEW CYTOTOXIC ANNONACEOUS ACETOGENIN FROM GONIOTHALAMUS-GIGANTEUS AND THE CONVERSION OF MONO-THF ACETOGENINS TO BIS-THF ACETOGENINS

A new Annonaceous acetogenin, gonionenin (1), has been isolated from the bark of Goniothalamus giganteus (Annonaceae). C-21/22 double bonds in 1 and in gigantetronenin (10) were oxidized and then cyclized to give pairs of adjacent bis-THF (4 and 7) and nonadjacent bis-THF (11 and 14) acetogenins, respectively. This is the first reported preparation of bis-THF Annonaceous acetogenins through double-bond epoxidation and cyclization from mono-THF acetogenins. The resulting bis-THF compounds (4, 7, 11, 14) showed enhanced bioactivities, versus 1 and 10, with 11 and 14 being over a billion times more cytotoxic than adriamycin against certain solid tumor cell lines.