title: Total Synthesis and Structural Reassignment of Aspergillomarasmine A.
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.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
authors.forename: Daohong
authors.initials: D
authors.lastname: Liao
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.|School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.
authors.forename: Shaoqiang
authors.initials: S
authors.lastname: Yang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.|School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.
authors.forename: Benke
authors.initials: B
authors.lastname: Hong
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China. xglei@pku.edu.cn.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Lei
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure
chemical_list: D001224:Aspartic Acid; C069862:aspergillomarasmine A
keywords: antibiotics; aspergillomarasmine A; metallo-β-lactamase; structural reassignment; total synthesis