Total Synthesis of Aquayamycin.

An efficient and practical total synthesis of aquayamycin has been accomplished. The highly oxidized and stereochemically complex tetracyclic ring system was constructed using three key reactions: 1) highly diastereoselective 1,2-addition of C-glycosyl naphthyllithium to a cyclic ketone, 2) indium-mediated site-selective allylation-rearrangement sequence of naphthoquinone, and 3) diastereoselective intramolecular pinacol coupling. This synthetic strategy offers a novel and efficient pathway to prepare aquayamycin-type angucycline antibiotics.