Biomimetic Synthesis of the Marine-Derived Thioalkaloids Dassonmycins A and B

A biomimetic synthesis of the marine thioalkaloids dassonmycins A and B is reported. The synthesis features a chemoselective reduction of a diketopiperazine to form a 2-piperazinone, which undergoes heteroannulation with naphthoquinone to yield dassonmycin A. Dassonmycin A undergoes slow cyclization to form dassonmycin B at physiological pH, supporting a biosynthesis hypothesis that this reaction could occur in the cytosol of the bacterial host species.