Concise synthesis of simplified aogacillin analogs reveals innate reactivity and synergy with aminoglycosides
Andrew R. LeBlanc, Jacqueline R. Smith, Audrey J. Isakov, John Bacsa, William M. Wuest · 2026
Read Concise synthesis of simplified aogacillin analogs reveals innate reactivity and synergy with aminoglycosides by Andrew R. LeBlanc, Jacqueline R. Smith, Audrey J. Isakov, John Bacsa, William M. Wuest (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/PMC13312816.txt.
Description
Andrew R. LeBlanc and colleagues report a 2026 chemistry study simplifying the aogacillins, natural products that make aminoglycoside antibiotics work far better against resistant bacteria. The original pair of compounds, isolated from a fungus, showed striking synergy, but their complexity slowed study, so the team set out to reach working analogs in just a few steps.
Their shortened routes delivered analogs in three to four steps. Testing showed the molecules permanently trap cysteine nucleophiles at a reactive enone warhead, the likely source of their power. The same warhead also leaves them open to unwanted cycloaddition side reactions. The authors therefore built redesigned analogs that quiet that side reactivity while keeping the sensitizing effect. The tuned compounds made MRSA respond to aminoglycosides at concentrations below the drugs' usual minimum inhibitory levels.
Catalog record
| CREATOR | Andrew R. LeBlanc, Jacqueline R. Smith, Audrey J. Isakov, John Bacsa, William M. Wuest |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 18599 |
| LICENSE | https://creativecommons.org/licenses/by/4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |