Towards chemical libraries of annonaceous acetogenins

Many of the Annonaceous acetogenins, particularly those containing a bis-THF moiety, exhibit outstanding cytotoxicity and pesticidal activity. Their remarkable structural diversity suggests that a complete chemical library of these compounds should be prepared and systematically screened. We show here several approaches to meet this synthetic challenge using the naked carbon skeleton strategy as well as a convergent synthesis. The key transformations include the Sharpless asymmetric dihydroxylation reaction, the Mitsunobu inversion of alcohols and ligand-assisted chirality transfer methods based on rhenium and vanadium oxides. These approaches provide an easy access to naturally occurring acetogenins (e.g. asimicin, bullatacin, trilobacin, rolliniastatin and solamin) as well as the non-natural isomers.