Total Synthesis and Activity of the Metallo--lactamase Inhibitor AspergillomarasmineA

Resistance to -lactam antibiotics is mediated primarily by enzymes that hydrolytically inactivate the drugs by one of two mechanisms: serine nucleophilic attack or metal-dependent activation of a water molecule. Serine -lactamases are countered in the clinic by several codrugs that inhibit these enzymes, thereby rescuing antibiotic action. There are no equivalent inhibitors of metallo--lactamases in clinical use, but the fungal secondary metabolite aspergillomarasmineA has recently been identified as a potential candidate for such a codrug. Herein we report the synthesis of aspergillomarasmineA. The synthesis enabled confirmation of the stereochemical configuration of the compound and offers a route for the synthesis of derivatives in the future.