Remarkably Efficient Synthesis of Bioactive Compounds Using New Synthons

利用我们独创的方法，已经实现了一些生物活性天然产物的短而高效的合成。利用我们原始的远程立体诱导方法，在Lewis酸存在下，醛与具有手性助剂的烯酮sily1-N， o -缩醛反应生成γ-羟基- A， β-不饱和亚胺，立体选择性合成了包括5-脂氧合酶抑制剂拉古那霉素、抗热利杆菌抗生素放线菌pyrone A和抗肿瘤药物哈弗芬金在内的线性链聚酮。在拉古那霉素和放线菌酮A的情况下，第一次合成是成功的，并且在最长的线性序列中，两种合成都只需要9个步骤。这些合成是非常短的和高度立体选择性的。此外，通过这些合成确定了放线素酮和拉古那霉素的绝对构型。还合成了多种芳香环化合物，包括信号素- 3a抑制剂vinaxanthone和内啡肽转化酶抑制剂TMC-66。它们都是第一次全合成。在vinaxanthone的全合成过程中，为了减少合成序列，假设并合成了生物遗传中间体。以中间产物为原料，高效地合成了维纳杉酮。TMC-66是一种具有两个手性中心的连续七环，通过在中心偶联两个具有三个环的部分并在分子内连续氧化偶联而合成的。该策略实现了高效的全合成，包括最长线性序列的9个步骤，并完成了TMC-66的绝对构型确定。因此，在这一资助下，生物活性天然产物包括线性链聚酮和多芳环化合物的合成研究相继得到了促进。应用于这些全合成的方法非常强大，可以在短时间内制造出生物活性化合物。这些研究结果使得立体选择合成相对分子质量为300~550的中等大小化合物在短期内容易获得，操作简单。通过这些全合成开发的新化学物质的研究正在进行中。少

Short and efficient syntheses of some bioactive natural products have been achieved by our original methodologies. Linear chain polyketides including 5-lipoxygenase inhibitor lagunamycin, anti Hericobacter Pyroli antibiotic actinonpyrone A, and antitumor khafrefungin have been synthesized stereoselectively by means of our original remote stereoinduction methodologies, the reaction between aldehyde and ketene sily1-N, O-acetal possessing a chiral auxiliary in the presence of Lewis acid to construct γ-hydroxy-a, β-unsaturated imide. In the cases of lagunamycin and actinopyrone A the first syntheses were achieved, and both syntheses took only nine steps in the longest linear sequence. These syntheses are remarkably short and highly stereoselective. Additionally, by these syntheses the absolute configurations of actinopyrone and lagunamycin were determined. Multiple aromatic rings compounds including semaphorin-3A inhibitor vinaxanthone and endotheline converting enzyme inhibitor TMC-66 ha … More ve also been synthesized. Both of them are the first total syntheses. In the total synthesis of vinaxanthone, biogenetical intermediary was assumed and synthesized to reduce the synthetic sequence. The efficient total synthesis of vinaxanthone was accomplished with the intermediary. TMC-66, the sequential seven rings having two chiral centers, was synthesized by coupling two parts, both having three rings, at the center and successive intramolecular oxidative coupling. This strategy lead to the efficient total synthesis, which included 9 steps in the longest linear sequence and was accomplished to determine the absolute configuration of TMC-66.Thus, synthetic studies on bioactive natural products including linear chain polyketides and multiple aromatic rings compounds have been promoted successively by this financial aid. Methodologies applied to these total syntheses are very powerful to make bioactive compounds in short steps. The results of these studies made stereoselective synthesis of medium size compounds possessing molecular weight 300~550 easy to get in a short term with simple handling.Studies on new chemistries developed through these total syntheses are in progress. Less