NOVEL MONO-TETRAHYDROFURAN RING ACETOGENINS, FROM THE BARK OF ANNONA-SQUAMOSA, SHOWING CYTOTOXIC SELECTIVITIES FOR THE HUMAN PANCREATIC-CARCINOMA CELL-LINE, PACA-2

The bark of Annona squamosa yielded three new mono-tetrahydrofuran (TH F) ring acetogenins, each bearing two flanking hydroxyls and a carbony l group at the C-9 position. These compounds were isolated using the b rine shrimp lethality assay as a guide for the bioactivity-directed fr actionation. (2,4-cis and trans)-Mosinone A (1) is a mixture of ketola ctone compounds bearing a threo/trans/threo ring relationship and a do uble bond two methylene units away from the flanking hydroxyl. The oth er two new acetogenins differ in their stereochemistries around the TH F ring; mosin B (2) has a threo/trans/erythro configuration across the ring, and mosin C (3) possesses a threo/cis/threo relative stereochem istry. Also found was annoreticuin-9-one (4), a known acetogenin that bears a threo/trans/threo ring configuration and a C-9 carbonyl and is new to this species. The structures were elucidated based on spectros copic and chemical methods. Compounds 1-4 all showed selective cytotox ic activity against the human pancreactic tumor cell line, PACA-2, wit h potency 10-100 times that of Adriamycin.