Total synthesis of (±)-naphthacemycin A9, possessing both antibacterial activity against methicillin-resistant Staphylococcus aureus and circumventing effect of β-lactam resistance

The total synthesis of KB-3346-5A 9 , named naphthacemycin A 9 , has been accomplished by combining the Dötz reaction and Suzuki–Miyaura cross coupling as well as employing Friedel–Crafts reaction with dienone-phenol rearrangement as key steps. We also describe the preparation of the simplified teta...

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Bibliographic Details
Published in:Journal of antibiotics 2017-05, Vol.70 (5), p.574-581
Main Authors: Hirose, Tomoyasu, Kojima, Yasuhiro, Matsui, Hidehito, Hanaki, Hideaki, Iwatsuki, Masato, Shiomi, Kazuro, Ōmura, Satoshi, Sunazuka, Toshiaki
Format: Article
Language:English
Subjects:
639/638/309/2144
639/638/403/977
Amides
Antibacterial activity
Antibiotic resistance
Bacteriology
Biomedical and Life Sciences
Bioorganic Chemistry
Chemical reactions
Cross coupling
Drug resistance
Friedel-Crafts reaction
Life Sciences
Medicinal Chemistry
Methicillin
Microbiology
Organic Chemistry
original-article
Phenols
Staphylococcus aureus
Staphylococcus infections
Structure-activity relationships
Synthesis
Vancomycin
β-Lactam antibiotics
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Summary:The total synthesis of KB-3346-5A 9 , named naphthacemycin A 9 , has been accomplished by combining the Dötz reaction and Suzuki–Miyaura cross coupling as well as employing Friedel–Crafts reaction with dienone-phenol rearrangement as key steps. We also describe the preparation of the simplified tetarimycin A and naphthacemycin A analogs as a model study, which coincidentally reveal unique properties of naturally occurring naphthacene-5,6,11(12 H )-trione framework. The synthesized compounds were evaluated for antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus (VRE) to elucidate their structure-activity relationships (SARs), the results of which agreed with a previously reported preliminary SAR study of tetarimycin A.
ISSN:0021-8820
1881-1469
DOI:10.1038/ja.2016.141