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

通过我们的原始方法，已经实现了一些生物活性天然产品的简短合成。 Linear chain polyketides include 5-lipoxygenase inhibitor lacunamycin, anti Hericobacter Pyroli antibiotic actinonpyrone A, and antitumor khafrefungin have been synthesized stereoselectively by means of our original remote stereoinduction methods, the reaction between aldehyde and ketene sily1-N, O-acetal possessing a chiral auxiliary在刘易斯酸的存在下以构建γ-羟基-A，β-未饱和酰亚胺。在lacunamycin和racunopyrone A的情况下，达到了第一批合成，并且两个合成在最长的线性序列中仅采取了9个步骤。这些合成非常短且高度立体选择性。另外，通过这些合成，确定了肌动酮和lacunamycin的绝对构型。多种芳族环化合物，包括Semaphorin-3a抑制剂vinaxanthone和内皮转化酶抑制剂TMC-66 HA…也合成了更多的芳香环。他们俩都是第一个总合成。在整体合成中，葡萄链酮，假定生物遗传学中间体并合成以减少合成序列。中间体的有效总合成是通过中间体完成的。 TMC-66是具有两个手性中心的顺序七个环，通过与两个均具有三个环的耦合以及成功的分子内氧化物偶联来合成。该策略导致有效的总合成，其中包括最长的线性序列中的9个步骤，并完成了TMC-66的绝对构型，因此，对生物活性天然产物的合成研究（包括线性链聚酮化合物和多个芳香环化合物）已通过此财政援助成功促进了。应用于这些总合成的方法学非常强大，可以在短步骤中制成生物活性化合物。这些研究的结果使得具有分子量的中等大小化合物的立体选择性合成300〜550在短期内易于使用简单处理。较少的

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