title: Total synthesis of (±)-naphthacemycin A9, possessing both antibacterial activity against methicillin-resistant Staphylococcus aureus and circumventing effect of β-lactam resistance.
abstract: The total synthesis of KB-3346-5A9, named naphthacemycin A9, 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(12H)-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.
authors.affiliation: Graduate School of Infection Control Sciences and Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Hirose
authors.affiliation: Graduate School of Infection Control Sciences and Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kojima
authors.affiliation: Graduate School of Infection Control Sciences and Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Graduate School of Infection Control Sciences and Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hanaki
authors.affiliation: Graduate School of Infection Control Sciences and Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Iwatsuki
authors.affiliation: Graduate School of Infection Control Sciences and Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Kazuro
authors.initials: K
authors.lastname: Shiomi
authors.affiliation: Graduate School of Infection Control Sciences and Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ōmura
authors.affiliation: Graduate School of Infection Control Sciences and Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sunazuka
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016983:Enterococcus / Q000187:drug effects*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D009279:Naphthacenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D020713:Vancomycin Resistance; D018440:beta-Lactam Resistance; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D009279:Naphthacenes; D047090:beta-Lactams; C000620671:naphthacemycin A9