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Updated: Jul 1, 2026

Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
Published on: April 18, 2019
Concise synthesis of simplified aogacillin analogs reveals innate reactivity and synergy with aminoglycosides
Andrew R LeBlanc1, Jacqueline R Smith1, Audrey J Isakov1
1Department of Chemistry, Emory University Atlanta GA 30322 USA wwuest@emory.edu.
Abstract:
Aogacillins (AOGs) A-B, two diastereomeric natural products isolated from Simplicillium sp. FKI-5985, were reported to have potent synergism with aminoglycoside antibiotics. Herein, we show that structural simplification expedites the synthesis of AOG analogs in 3-4 steps. Furthermore, we demonstrate that these compounds irreversibly trap cysteine nucleophiles at an electrophilic enone warhead but are also susceptible to [4 + 2] cycloadditions. Therefore, strategically designed AOG analogs were constructed to mitigate side reactivity and sensitize MRSA to aminoglycosides at sub-MIC concentrations.
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