TOWARDS CHEMICAL LIBRARIES OF ANNONACEOUS ACETOGENINS

Many of the Annonaceous acetogenins, particularly those containing a b is-THF moiety, exhibit outstanding cytotoxicity and pesticidal activit y. Their remarkable structural diversity suggests that a complete chem ical library of these compounds should be prepared and systematically screened. We show here several approaches to meet this synthetic chall enge using the naked carbon skeleton strategy as well as a convergent synthesis. The key transformations include the Sharpless asymmetric di hydroxylation reaction, the Mitsunobu inversion of alcohols and ligand -assisted chirality transfer methods based on rhenium and vanadium oxi des. These approaches provide an easy access to naturally occurring ac etogenins (e.g. asimicin, bullatacin, trilobacin, rolliniastatin and s olamin) as well as the non-natural isomers.