IN-VITRO ANTITUMOR ACTIVITIES OF NEW SYNTHETIC BISTETRAHYDROFURAN DERIVATIVES AS ANALOGS OF ANNONACEOUS ACETOGENINS

We investigated the in vitro antitumor activities toward mouse and hum an cell lints of optically active synthetic bistetrahydrofuran (bis-TH F) derivatives as analogs of Annonaceous acetogenins, which contain bi s-THF, long unbranched alkyl chains, hydroxyl groups, and an alpha,bet a-unsaturated gamma-lactone. These bis-THF derivatives were synthesize d in a stereocontrolled manner, and have several modified structures a t the alkyl side chains. We found that: 1) the unsaturated gamma-lacto ne contributes to high potency in combination with the other less-func tionalized alkyl chain, 2) the same absolute configuration of the bis- THF skeleton as that of the natural products produces more potent acti vity than the counterpart, 3) the alkyl chains and hydroxyl groups are crucial for exhibiting antitumor activity 4) hydroxyl groups adjacent to the bis-THF skeleton may be replaced by amino or acylamino groups.