Stereocontrolled Total Synthesis of (+)-Isolaurenidificin and (-)-Bromlaurenidificin.

We report the first total syntheses of (+)-isolaurenidificin (1) and (-)-bromlaurenidificin (2), the latest acetogenins of the 2,6-dioxabicyclo[3.3.0]octane class. The synthesis features a completely stereoselective one-pot epimerization-ring contraction to establish the cis configuration with respect to C10-H and C12-H of the tetrahydrofuran ring. Six stereogenic centers and an olefin geometry were constructed in a highly stereoselective manner. Absolute configurations of the natural products were deduced by the comparison of NMR data and specific rotations.