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

Asimicin and a new cyrotoxic Annonaceous acetogenin, venezenin [1], we re 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 tetrahyd rofuran (THF) or epoxide rings and possessing a double bond located tw o methylenes away from a vicinal diol in the hydrocarbon chain. The st ructure 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-TH F acetogenins were prepared from 1. These acetogenins showed cytotoxic ity, comparable or superior ro adriamycin, against three human solid t umor cell lines. Reduction of the 10-keto of 1 to the racemic OH-10 de rivative enhanced the bioactivity, as did the conversion oi 1 to 6 and 7. Venezenin [1], like other Annonaceous acetogenins, showed inhibiti on of oxygen uptake by rat liver mitochondria and demonstrated that th e THF ring may net be essential to this mode of action.