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We report the first total synthesis and stereochemical configuration reassignment of aspergillomarasmine A

Abstract: The increase and spread of Gram-negative bacteria resistant to almost all currently available β-lactam antibiotics is a major global health problem. The cause for drug resistance is primarily due to the acquisition of metallo-β-lactamases such as NDM-1. Aspergillomarasmine A (AMA), a fungal natural product, is an inhibitor of NDM-1 and has shown promising in […]

Abstract: The increase and spread of Gram-negative bacteria resistant to almost all currently available β-lactam antibiotics is a major global health problem. The cause for drug resistance is primarily due to the acquisition of metallo-β-lactamases such as NDM-1. Aspergillomarasmine A (AMA), a fungal natural product, is an inhibitor of NDM-1 and has shown promising in vivo therapeutic potential in mouse model infected with NDM-1 expressing Gram-negative bacteria. Here, we report the first total synthesis and stereochemical configuration reassignment of aspergillomarasmine A. The synthesis highlights a flexible route and an effective strategy to achieve the required oxidation state at late stage. This modular route is amenable to the efficient preparation of analogs for the development of metallo-β-lactamase inhibitors to potentiate β-lactam antibiotics.toc-AMA

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toc-1Link: http://onlinelibrary.wiley.com/doi/10.1002/anie.201509960/full