Enantioselective Total Synthesis of Andrographolide and 14-Hydroxy-Colladonin: Carbonyl Reductive Coupling andtrans-Decalin Formation by Hydrogen Transfer

An enantioselective total synthesis of the labdane diterpene andrographolide, the bitter principle of the herb Andrographis paniculata (known as King of Bitters), was accomplished in 14 steps (LLS). Key transformations include iridium-catalyzed carbonyl reductive coupling to form the quaternary C4 stereocenter, diastereoselective alkene reduction to establish thetrans-decalin ring, and carbonylative lactonization to install the alpha-alkylidene-beta-hydroxy-gamma-butyrolactone.