Remarkably Efficient Synthesis of Bioactive Compounds Using New Synthons

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有效的合成。利用我们独创的远程立体诱导方法，在路易斯酸存在下醛和烯酮硅缩1-N，O-缩醛反应生成γ-羟基-a，β-不饱和亚胺，立体选择性地合成了包括5-脂氧合酶抑制剂拉古霉素、抗幽门螺杆菌抗生素放线菌酮A和抗肿瘤红曲霉菌素在内的直链聚酮。在拉古霉素和放线菌酮A的情况下实现了第一次合成，两个合成都只用了最长的线性序列中的九步。这些合成非常短，并且具有很高的立体选择性。此外，通过这些合成，确定了放线吡喃酮和拉古霉素的绝对构型。多芳环化合物，包括信号素-3A抑制剂维黄原酮和内皮素转换酶抑制剂TMC-66 HA…还合成了更多的化合物。这两种化合物都是首次全合成。在乙烯黄原酮的全合成中，假设合成了生物合成中间体，减少了合成顺序。在此中间体的作用下，实现了乙烯黄原酮的高效全合成。TMC-66是具有两个手性中心的连续七个环，通过在中心连接两个都有三个环的部分和连续的分子内氧化偶联而合成的。这一策略导致了高效的全合成，包括最长的线性序列中的9个步骤，并完成了对TMC-66绝对构型的确定。因此，这一资助先后促进了包括直链多酮和多芳环化合物在内的生物活性天然产物的合成研究。应用于这些全合成的方法非常强大，可以在很短的步骤内合成具有生物活性的化合物。这些研究结果使分子量为300~550的中等尺寸化合物的立体选择性合成易于在短期内获得，操作简单。通过这些全合成开发新的化学成分的研究正在进行中。较少

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