Total Synthesis and Structural Reassignment of AspergillomarasmineA

The increase and spread of Gram-negative bacteria that resistant are to almost all currently available -lactam antibiotics is a major global health problem. The primary cause for drug resistance is the acquisition of metallo--lactamases such as metallo--lactamase-1 (NDM-1). The fungal natural product aspergillomarasmineA (AMA), a fungal natural product, is an inhibitor of NDM-1 and has shown promising invivo therapeutic potential in a mouse model infected with NDM-1-expressing Gram-negative bacteria. The first total synthesis and stereochemical configuration reassignment of aspergillomarasmineA is reported. The synthesis highlights a flexible route and an effective strategy to achieve the required oxidation state at a late stage. This modular route is amenable to the efficient preparation of analogues for the development of metallo--lactamase inhibitors to potentiate -lactam antibiotics.National High Technology Project 973 [2015CB856200]; NNSFC [21222209, 91313303, 21472010]SCI(E)ARTICLExglei@pku.edu.cn134291-42955