Aza-Wacker Cyclization Toward the Bridged Core of FR901483

Abstract A nine-step synthetic route to access the tricyclic core of FR901483 is reported, featuring a key aza-Wacker cyclization step to construct an α-tertiary amine (ATA) in the bridged structure. The aza-Wacker protocol can tolerate both exocyclic and endocyclic double bonds, providing viable access to various bridged bicyclic rings bearing an ATA (e.g., 6-azabicyclo[3.2.1]octane, 7-azabicyclo[3.3.1]nonane, and 7-azabicyclo[4.2.1]nonane) in good to excellent yields. The synthetic studies presented herein enable structural derivatization of FR901483 to further exploit its compelling biological activities.