Total Synthesis of (+)-Malbrancheamide B Employing a Bioinspired Strategy

Prenylated indole alkaloids are a class of secondary metabolites isolated from various terrestrial and marine fungi. The common complex structure, featuring a diazabicyclo[2.2.2]octane scaffold fused to a tetrahydrocarbazole unit, and the numerous biological activities make these compounds attractive synthetic targets. In the present work an asymmetric total synthesis of (+)-malbrancheamide B is reported. Key steps are bioinspired diketopiperazine (DKP) assembly, a stereoselective oxidative radical cyclization, which gives access to the three-dimensional bridged diketopiperazine precursor and an intramolecular Friedel-Crafts cyclization providing the hexacyclic skeleton of malbrancheamide B.