Total Synthesis and Structural Reassignment of Aspergillomarasmine A. (23rd November 2015)

• Record Type: Journal Article
• Authors: Liao, Daohong; Yang, Shaoqiang; Wang, Jianyu; Zhang, Jian; Hong, Benke; Wu, Fan; Lei, Xiaoguang
• Is Part Of: Angewandte Chemie. Volume 128:Number 13(2016)
• Page Start: 4363
• Page End: 4367
• Publication Date: 2015-11-23
• Subjects: Antibiotika -- Aspergillomarasmin A -- Metallo-β-lactamase -- Strukturrevision -- Totalsynthesen; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201509960
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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.