5 NOVEL MONO-TETRAHYDROFURAN RING ACETOGENINS FROM THE SEEDS OF ANNONA-MURICATA

Bioactivity-directed fractionation of the seeds of Annona muricata L. (Annonaceae) resulted in the isolation of five new compounds: cis-anno nacin (1), cis-annonacin-10-one (2), cis-goniothalamicin (3), arianaci n (4), and javoricin (5). Three of these (1-3) are among the first cis mono-tetrahydrofuran ring acetogenins to be reported. NMR analyses of published model synthetic compounds, prepared cyclized formal acetals , and prepared Mosher ester derivatives permitted the determinations o f absolute stereochemistries. Bioassays of the pure compounds, in the brine shrimp test, for the inhibition of crown gall tumors, and in a p anel of human solid tumor cell lines for cytotoxicity, evaluated relat ive potencies. Compound 1 was selectively cytotoxic to colon adenocarc inoma cells (HT-29) in which it was 10 000 times the potency of adriam ycin.