Premium
Total Synthesis and Structural Reassignment of Aspergillomarasmine A
Author(s) -
Liao Daohong,
Yang Shaoqiang,
Wang Jianyu,
Zhang Jian,
Hong Benke,
Wu Fan,
Lei Xiaoguang
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201509960
Subject(s) - total synthesis , natural product , antibiotics , bacteria , chemistry , in vivo , combinatorial chemistry , stereochemistry , lactam , microbiology and biotechnology , drug resistance , gram , computational biology , biology , biochemistry , genetics
The increase and spread of Gram‐negative bacteria that resistant are to almost all currently available β‐lactam antibiotics is a major global health problem. The primary cause for drug resistance is the acquisition of metallo‐β‐lactamases such as metallo‐β‐lactamase‐1 (NDM‐1). The fungal natural product aspergillomarasmine A (AMA), a fungal natural product, is an inhibitor of NDM‐1 and has shown promising in vivo therapeutic potential in a mouse model infected with NDM‐1‐expressing Gram‐negative bacteria. The first total synthesis and stereochemical configuration reassignment of aspergillomarasmine A 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‐β‐lactamase inhibitors to potentiate β‐lactam antibiotics.