Total Synthesis and Activity of the Metallo‐β‐lactamase Inhibitor Aspergillomarasmine A. (28th December 2015)

• Record Type: Journal Article
• Authors: Koteva, Kalinka; King, Andrew M.; Capretta, Alfredo; Wright, Gerard D.
• Is Part Of: Angewandte Chemie. Volume 128:Number 6(2016)
• Page Start: 2250
• Page End: 2252
• Publication Date: 2015-12-28
• Subjects: Antibiotikaresistenz -- Inhibitoren -- Konfigurationsbestimmung -- Metallo-β-lactamasen -- Totalsynthesen; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201510057
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Resistance to β‐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 β‐lactamases are countered in the clinic by several codrugs that inhibit these enzymes, thereby rescuing antibiotic action. There are no equivalent inhibitors of metallo‐β‐lactamases in clinical use, but the fungal secondary metabolite aspergillomarasmine A has recently been identified as a potential candidate for such a codrug. Herein we report the synthesis of aspergillomarasmine A. The synthesis enabled confirmation of the stereochemical configuration of the compound and offers a route for the synthesis of derivatives in the future.