Concise Chemoenzymatic Synthesis of Fasamycin A

We report the development of a chemoenzymatic approach toward 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 in a Sammes annulation 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.

Automated summary

A novel chemoenzymatic approach was developed for the synthesis of fasamycin A, a halogenated naphthacenoid with activities against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. The synthesis involved combining two fragments through a Sammes annulation to form a dimethylnaphthacenone system, followed by enzymatic halogenation to introduce the necessary chlorine substituent at a later stage.