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

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全合成，如Preussin，FR901464，Pionetin等。相关的类似物包括生物素标记的探针自由基醇，Pionetin。合成了FR901464和Preussin，并将其提交给生物学研究。以FR901464为例，发现一些类似物比天然产物具有更强的生物活性，并鉴定了目标蛋白。对这些探针和相关类似物的生物功能分析的进一步研究正在进行中。以吡罗尼汀为例，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是相当重要的。2)我们还研究了与植物保护和植物生理相关的物质的合成，并利用自由基环化方法生成了基本的碳骨架，从而开发了一种有效的昆虫拒食剂印楝素的合成路线。我们正试图将这种方法应用到实际系统中。在脱氧烟碱酸(DMA)及其类似物中，我们发现一些类似物比DMA更有活性，现在我们正在将这些物质应用于田间试验。通过两年的时间，我们完成了合成非常有趣的具有显著生物活性的分子，并通过与生物学家、生物化学家和生理学家的合作，我们将积累有趣的生物学数据。我们将继续进行更多的研究。

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.