Hirose Tomoyasu, Sunazuka Toshiaki, Tsuchiya Satoshi, Tanaka Toshiaki, Kojima Yasuhiro, Mori Ryuma, Iwatsuki Masato, Omura Satoshi
Kitasato Institute for Life Science, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
Chemistry. 2008;14(27):8220-38. doi: 10.1002/chem.200801024.
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.
本文描述了胍地诺胺类化合物绝对构型的确定，这些化合物是新型环状胍基天然产物，是细菌III型分泌系统（TTSS）的抑制剂。任何能够阻断细菌TTSS的化合物都有可能成为理想的抗感染药物。胍地诺胺类化合物可靠的不对称合成揭示了它们的绝对构型，若没有这种合成方法，这些构型是无法确定的。我们的报告不仅描述了标题化合物的不对称全合成，还展示了光学纯形式的三取代哌嗪酮核心的新颖简洁合成方法。我们方法的新颖之处在于分子内S(N)2环化反应，该反应利用三苯基膦（PPh(3)）和碘（I(2)）构建独特的五元环状胍亚结构。
