Total synthesis and determination of the absolute configuration of guadinomines B and C2.
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.
Hirose
Tomoyasu
T
Kitasato Institute for Life Science, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
Sunazuka
Toshiaki
T
Tsuchiya
Satoshi
S
Tanaka
Toshiaki
T
Kojima
Yasuhiro
Y
Mori
Ryuma
R
Iwatsuki
Masato
M
Omura
Satoshi
S
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
D004151:Dipeptides; D048289:Imidazolidines; C530703:guadinomine B; C533544:guadinomine C2