Ichikawa Satoshi
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Chem Pharm Bull (Tokyo). 2008 Aug;56(8):1059-72. doi: 10.1248/cpb.56.1059.
Synthetic nucleoside chemistry based on nucleoside natural products synthesis were described. First, a samarium diiodide (SmI 2)-promoted aldol reaction with the use of alpha-phenylthioketone as an enolate was developed. The characteristics of this 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 natural products, and herbicidin B and fully protected tunicaminyluracil, which were undecose nucleoside natural products, were synthesized. Next, the synthetic methodology of the caprazamycins, which are promising antibacterial nucleoside natural products, was also developed by the strategy including beta-selective ribosylation without using a neighboring group participation. Our synthetic route provided a range of key analogues with partial structures to define the pharmacophore. Simplification of the caprazamycins was further pursued to develop diketopiperazine analogs.
描述了基于核苷天然产物合成的合成核苷化学。首先，开发了一种使用α-苯硫酮作为烯醇盐的二碘化钐（SmI₂）促进的羟醛反应。该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天然产物的有力反应，并且合成了除草菌素B和完全保护的衣霉素基尿嘧啶，它们是十一碳核苷天然产物。接下来，还通过不使用邻基参与的β-选择性核糖基化策略开发了有前景的抗菌核苷天然产物卡普霉素的合成方法。我们的合成路线提供了一系列具有部分结构的关键类似物以确定药效团。进一步对卡普霉素进行简化以开发二酮哌嗪类似物。
