VENEZENIN - A NEW BIOACTIVE ANNONACEOUS ACETOGENIN FROM THE BARK OF XYLOPIA-AROMATICA

Asimicin and a new cyrotoxic Annonaceous acetogenin, venezenin [1], were isolated from the bark of Xylopia aromatica by bioactivity-directed fractionation using lethality to brine shrimp. Compound 1 represents an unusual type of C-3, Annonaceous acetogenin,lacking either tetrahydrofuran (THF) or epoxide rings and possessing a double bond located two methylenes away from a vicinal diol in the hydrocarbon chain. The structure of 1 mas elucidated by H-1- and C-13-nmr, COSY, single-relayed COSY, and by HMBC techniques, and derivatization. Annomontacin 10-one [6] and 18/21-cis-annomontacin-10-one [7], two semi-synthetic mono-THF acetogenins were prepared from 1. These acetogenins showed cytotoxicity, comparable or superior ro adriamycin, against three human solid tumor cell lines. Reduction of the 10-keto of 1 to the racemic OH-10 derivative enhanced the bioactivity, as did the conversion oi 1 to 6 and 7. Venezenin [1], like other Annonaceous acetogenins, showed inhibition of oxygen uptake by rat liver mitochondria and demonstrated that the THF ring may net be essential to this mode of action.