SYNTHESIS OF CYTOTOXIC FLUORINATED QUASSINOIDS

The C-15 senecioyl side chain of brusatol was interchanged with fluori nated acyl groups, and the C-3 hydroxy group of bruceolide was esterif ied with fluorinated acyl chlorides. These fluorinated quassinoids 11, 12, 13, and 17 showed significant cytotoxic activity against eight hu man cancer cell lines including small and non-small cell lung, colon, CNS, ovarian and renal cancers, leukemia, and melanoma with 17 being a bout 100 times more potent than 11, 12, and 13. The activity of 17 was similar to that of bruceantin (1) in this in vitro cell line panel. ( C) 1997 Elsevier Science Ltd.