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Updated: Jun 21, 2025

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An enantioselective formal synthesis of thienamycin
Jamie L Breunig1, You-Chen Lin1, Joshua G Pierce1
1Department of Chemistry and Integrative Sciences Initiative, NC State University, Raleigh, North Carolina, 27695, United States.
Abstract:
Thienamycin is a carbapenem antibiotic with potent activity against gram-negative and gram-positive bacteria. Due to its promising activity but lack of chemical stability, thienamycin serves as inspiration for new synthetic antibiotic scaffolds. In this study, we report a nine-step enantioselective formal synthesis of thienamycin. Our route utilizes an asymmetric reduction, enabled by NaBH4 and D-tartaric acid, followed by a series of diastereoselective reactions to access the key azetidinone precursor to thienamycin. This azetidinone precursor could be used as an intermediate to further develop and expand the scope of next-generation beta-lactam antibiotic scaffolds.
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