Remarkably Efficient Synthesis of Bioactive Compounds Using New Synthons

使用新合成子非常有效地合成生物活性化合物

• 批准号: 17550049
• 负责人: HOSOKAWA Seijiro
• 金额: $ 2.3万
• 依托单位: Waseda University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17550049/
• 关键词: remote stereoinduction; vinyl ketene N, O-acetal; natural product synthesis; total synthesis; bioactive natural product; multiple aromatic rings compound; synthon; シリルケテン-N,O-アセタール; アクチノピロンA; 遠隔不斉誘導反応; 超効率的合成; 精密合成; 生理活性物質; 2-メトキシ-4-ピロン

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

通过我们独创的方法，我们已经实现了一些生物活性天然产物的快速高效合成，包括5-脂氧合酶抑制剂拉古霉素、抗幽门螺杆菌抗生素actinonpyrone A和抗肿瘤药物khafungin，这些都是通过我们独创的远程立体诱导方法进行立体选择性合成的。醛与烯酮甲硅烷基1-N,O-缩醛之间的反应，具有手性在路易斯酸存在下构建γ-羟基-α，β-不饱和酰亚胺在拉古霉素和放线菌酮A的情况下实现了第一次合成，并且这两种合成在最长的线性序列中仅花费了九步。此外，通过这些合成，确定了放线菌酮和拉古霉素的绝对构型，包括。 semaphorin-3A抑制剂vinaxanthone和内皮素转换酶抑制剂TMC-66 ha… More也已合成。在vinaxanthone的全合成中，假定并合成了生物中间体，以减少合成顺序。通过偶联合成了具有两个手性中心的连续七环TMC-66，完成了vinaxanthone的有效全合成。两个部分，均具有三个最长的环，位于中心和连续的分子内氧化偶联。该策略导致全合成，其中包括有效线性序列中的 9 个步骤，并完成确定 TMC-66 的绝对构型。这项财政援助成功地促进了包括直链聚酮化合物和多芳环化合物在内的生物活性天然产物的合成研究，这些研究的结果非常有效，适用于这些全合成。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的新化学物质的研究正在进行中。

项目成果

The first total synthesis of vinaxanthone, a fungus metabolite possessing multiple bioactivities

• DOI: 10.1246/cl.2007.10
• 发表时间: 2007-01
• 期刊: Chemistry Letters
• 影响因子: 1.6
• 作者: K. Tatsuta;S. Kasai;Y. Amano;Takahiro Yamaguchi;M. Seki;Seijiro Hosokawa

The first total synthesis and structural determination of actinopyrone A

• DOI: 10.1016/j.tetlet.2006.05.028
• 发表时间: 2006-07-24
• 期刊: TETRAHEDRON LETTERS
• 影响因子: 1.8
• 作者: Hosokawa, Seijiro;Yokota, Kazuya;Tatsuta, Kuniaki
• 通讯作者: Tatsuta, Kuniaki