title: Total synthesis and determination of the absolute configuration of guadinomines B and C2.
abstract: This article describes the determination of the absolute configurations of the guadinomines, which are novel cyclic guanidyl natural products that are inhibitors of the type III secretion system (TTSS) of bacteria. Any compound that interrupts the TTSS of bacteria is potentially an ideal anti-infectious drug. The reliable asymmetric synthesis of guadinomines has revealed their absolute configurations, which could not have been defined without this synthetic approach. Our report not only describes the asymmetric total synthesis of the title compounds, but also demonstrates the novel concise synthesis of tri-substituted piperazinone cores as optically pure forms. The novel feature of our method is an intramolecular S(N)2 cyclization that uses PPh(3) and I(2) to construct the unique 5-membered cyclic guanidine substructure.
authors.affiliation: Kitasato Institute for Life Science, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Hirose
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sunazuka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kojima
authors.forename: Ryuma
authors.initials: R
authors.lastname: Mori
authors.forename: Masato
authors.initials: M
authors.lastname: Iwatsuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
mesh_terms: D003500:Cyclization; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D048289:Imidazolidines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D012015:Reference Standards; D013237:Stereoisomerism
chemical_list: D004151:Dipeptides; D048289:Imidazolidines; C530703:guadinomine B; C533544:guadinomine C2