Annojahnin from Annona jahnii: A possible precursor of mono-tetrahydrofuran acetogenins

A new cytotoxic Annonaceous acetogenin, annojahnin (1), was isolated from t he twigs of Annona jahnii (Annonaceae) by bioactivity-directed fractionatio n using lethality to brine shrimp. Compound, 1 represents an unusual type o f C-37 Annonaceous acetogenin, lacking either tetrahydrofuran (THF) or epox ide rings, bearing a keto group at C-10, and possessing a double bond locat ed two methylenes away from a vicinal diol. The structure and absolute conf iguration of 1 were elucidated by H-1 and C-13 NMR, COSY, and single-relaye d COSY and from chemical derivatives. 4-Deoxy-18/21-trans-annomontacin 10-o ne (4) and 4-deoxy-18/21-cis-annomontacin-10-one (5), two semisynthetic mon o-THF acetogenins, were prepared from 1 by reactions that mimic the biogene tic pathways. These acetogenins showed selective cytotoxicities, comparable or superior to adriamycin, among six human solid tumor cell lines. Reducti on of the 10-keto of 1, to the racemic 10-OH derivative (3), retained the b ioactivities as did the conversion of 1 to 4 and 5. (C) 1998 Elsevier Scien ce Ltd. All rights reserved.