Ichikawa Satoshi
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Yakugaku Zasshi. 2006 Aug;126(8):579-95. doi: 10.1248/yakushi.126.579.
Some of nucleoside antibiotics include complex structures as well as sensitive functionality, which are challenging targets for organic chemists. Among complex nucleoside antibiotics, there are also good drug candidates because they possess a variety of interesting biological properties. Herbicidin B and fully protected tunicaminyluracil, which were undecose nucleoside antibiotics, were synthesized using a samarium diiodide (SmI(2)) mediated aldol reaction with the use of alpha-phenylthioketones as enolate sources. The characteristics of the SmI(2)-mediated aldol reaction are that the enolate can be regioselectively generated and the aldol reaction proceeds under near neutral condition. This reaction is proved to be a powerful reaction for the synthesis of complex nucleoside antibiotics. The synthesis of caprazol, the core structure of caprazamycins, was conducted by the strategy including beta-selective ribosylation without using a neighboring group participation and the construction of a diazepanone by a modified reductive amination. Our synthetic route would provide a range of key analogues with partial structures to define the pharmacophore, which can be a lead for the development of more effective anti-bacterial agents.
一些核苷类抗生素具有复杂的结构以及敏感的官能团，这对有机化学家来说是具有挑战性的目标。在复杂的核苷类抗生素中，也有很好的候选药物，因为它们具有多种有趣的生物学特性。除草菌素B和全保护的衣霉素基尿嘧啶，它们是十一碳核苷类抗生素，是使用二碘化钐（SmI₂）介导的羟醛反应，以α-苯硫酮作为烯醇盐源合成的。SmI₂介导的羟醛反应的特点是可以区域选择性地生成烯醇盐，并且羟醛反应在近中性条件下进行。该反应被证明是合成复杂核苷类抗生素的有力反应。卡普霉素核心结构卡普唑的合成是通过包括β-选择性核糖基化而不使用邻基参与以及通过改良的还原胺化构建二氮杂环庚酮的策略进行的。我们的合成路线将提供一系列具有部分结构的关键类似物来确定药效团，这可以作为开发更有效的抗菌剂的先导。
