Concise Chemoenzymatic Synthesis of Fasamycin A

We report the development of a chemoenzymatic approach towards fasamycin A, a halogenated naphthacenoid that exhibits activities against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. The synthesis was accomplished in a convergent manner: two fragments were combined together via Michael−Dieckmann condensation to afford a dimethylnaphthacenone system. Finally, an enzymatic halogenation was employed to introduce the requisite chlorine substituent of the natural product at a late stage.