Synthetic Studies on Optically Active Substances Directed towards the Creation of Novel Functional Materials

光学活性物质的合成研究，旨在创造新型功能材料

• 批准号: 12460050
• 负责人: KITAHARA Takeshi
• 金额: $ 9.28万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12460050/
• 关键词: Irone-Chelator; Synthesis of Optically Active Substances; Structure-Activity Relationship; Inhibitors of Cell-Cycle Progression; Insect Antifeedants; Plant Growth Regulators; Biotinylated Derivatives; Antitumor Substances; 昆虫摂食阻害物質; 幼弱ホルモン生合成阻害 /

1) Syntheses of enzyme inhibitors and cell-cycle inhibitors were studied. Total syntheses of several inhibitors have been accomplished during these two years, for example, preussin, FR901464, pironetin, etc. Related analogs including biotinylated probes of radicicol, pironetin. FR901464 and preussin were synthesized and submitted to biological studies. In the case of FR901464, it was found that some analogs were much more biologically active than natural product and also target protein was identified. Further studies on the analysis of biological functions of these probes as well as related analogs are under investigation. In the case of pironetin, we found that this compound binds to tublin selectively and also did precise structure-activity relationship and found stereochemistry of side chain is rather important.2) Syntheses of substances related to plant protection and plant physiology are also studied and we developed the route to azadirachtin, a potent insect-antifeedant, by exploiting the radical cyclization method to create basic carbon skeleton. We are trying to apply this method to the real system. In the case of deoxymugineic acid (DMA) and analogs, we found very interesting results that some analogs are more active than DMA and we are now applying these substances for field test.Through two years, we accomplished to synthesize very interesting molecules with remarkable bioactivities and by collaborating with biologists, biochemists and physiologists, we are going to accumulate interesting biological data. We will continue these studies more.

1)研究了酶抑制剂和细胞周期抑制剂的合成。这两年完成了多种抑制剂的全合成，例如preussin、FR901464、pironetin等。相关类似物包括根赤霉素、pironetin的生物素化探针。合成了 FR901464 和 preussin 并提交给生物学研究。以FR901464为例，我们发现一些类似物比天然产物具有更高的生物活性，并且还鉴定出了目标蛋白。对这些探针以及相关类似物的生物学功能分析的进一步研究正在进行中。就pironetin而言，我们发现该化合物选择性地与微管蛋白结合，并进行了精确的构效关系，发现侧链的立体化学相当重要。2）还研究了与植物保护和植物生理学相关的物质的合成，我们通过利用自由基环化方法创建基本碳骨架，开发了印楝素（一种有效的昆虫拒食剂）的路线。我们正在尝试将此方法应用到实际系统中。就脱氧麦根酸（DMA）及其类似物而言，我们发现了非常有趣的结果，一些类似物比DMA更具活性，我们现在正在将这些物质进行现场测试。通过两年的时间，我们成功合成了具有显着生物活性的非常有趣的分子通过与生物学家、生物化学家和生理学家合作，我们将积累有趣的生物学数据。我们将继续更多地进行这些研究。