Remarkably Efficient Synthesis of Bioactive Compounds Using New Synthons

利用我们独创的合成方法，已经实现了一些具有生物活性的天然产物的快速高效合成。利用我们独创的远程立体诱导方法，在刘易斯酸存在下，醛与烯酮甲硅烷基1-N，O-缩醛反应生成γ-羟基-α，β-不饱和酰亚胺，立体选择性地合成了5-脂氧合酶抑制剂拉古霉素、抗赫氏菌的Pyroli抗生素放线菌酮A和抗肿瘤的卡氟芬净等直链聚酮化合物。在拉古那霉素和放线菌酮A的情况下，第一个合成实现，和两个合成只需要九个步骤中最长的线性序列。这些合成是非常短和高度立体选择性。此外，通过这些合成确定了放线菌吡喃酮和拉古那霉素的绝对构型。包括脑信号蛋白-3A抑制剂vinaxanthone和内皮素转化酶抑制剂TMC-66的多芳环化合物 ...更多信息 也被合成了。两者都是第一次全合成。在合成过程中，假设并合成了生物中间体，减少了合成步骤。以该中间体为原料，实现了vinaxanthone的高效全合成。TMC-66，具有两个手性中心的连续七个环，通过在中心处偶联两个均具有三环的部分和连续的分子内氧化偶联来合成。该策略实现了最长线性序列9步全合成，并成功地确定了TMC-66的绝对构型，从而推动了包括直链聚酮化合物和多芳香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，可以在短步骤中制备生物活性化合物。这些研究结果使得分子量为300~550的中等分子量化合物的立体选择性合成在短时间内容易得到，操作简单，由此开发的新化学研究正在进行中。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