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。在这两年中，已经完成了几种抑制剂的总合成，例如普雷塞蛋白，FR901464，二铁蛋白等。相关的类似物，包括radicicol，pironetin的生物素化探针。 FR901464和Preussin合成并提交生物学研究。在FR901464的情况下，发现某些类似物比天然产物更具生物活性，并且还鉴定了靶蛋白。研究了这些探针生物学功能以及相关类似物的进一步研究。在二铁蛋白的情况下，我们发现这种化合物有选择地与tublin结合，并且还进行了精确的结构活性关系，并发现侧链的立体化学相当重要。2）与植物保护和植物生理相关的物质的合成，我们还开发了一种通过启用了Azadirachtin，一种有效的昆虫式骨骼，可以启用Azadirachtin的途径。我们正在尝试将此方法应用于真实系统。对于脱氧氨甘油酸（DMA）和类似物，我们发现了非常有趣的结果，某些类似物比DMA更活跃，现在我们正在将这些物质应用于现场测试。通过两年，我们完成了与生物学家，生物学家和生物学学家和生物学的合作，使非常有趣的分子合成非常有趣的分子，我们可以累积地累积数据。我们将继续进行这些研究。