Drug creation involving hybrid type of low molecular weight biomolecules as lead compounds

涉及混合型低分子量生物分子作为先导化合物的药物生产

• 批准号: 12672079
• 负责人: NAITO Takeaki
• 金额: $ 2.11万
• 依托单位: Kobe Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672079/
• 关键词: sugar; amino acid; radical; oxime ether; Dysiherbaine; Wittig rearrangement; 核酸塩基; ワンポット; デシヘルベイン

Research for exploring new lead compounds for new drugs has focused to one component of biological compounds and not to hybrid components so far. We started our project to develop the most efficient and practical synthetic method for biological hybrid compounds which consist of amino acids, sugars, and nucleic bases.New synthetic method for amino acids and the related peptides has been developed via the route involving radical addition-cyclization of oxime ethers connected with olefins. The products were converted smoothly into β-amino acids.We also investigated construction of sugar parts by the radical reactions of the unprotected natural sugars. Stannyl radical addition-cyclization of oxime ethers connected with the carbonyl group proceeded smoothly to afford cyclic amino alcohols which were converted into aminocyclitols. The radical reaction was found to proceed via the most stable transition state involving minimum 1, 3-allylic strain.Formal synthesis of Dysiherbine was completed via two key reactions which are 1, 2-Wittig rearrangement and asymmetric hydroxylation respectively.

探索新药物的新铅化合物的研究已集中在生物学化合物的一个成分上，而不是迄今为止混合成分。我们启动了我们的项目，以开发由氨基酸，糖和核碱基组成的生物杂种化合物的最有效，最实用的合成方法。氨基酸的New合成方法和相关的辣椒是通过涉及与olefins相关的氧气的自由基添加剂开发的。将产物平滑地转化为β-氨基酸。我们还通过未保护的天然糖的根本反应研究了糖的构成。与羰基相关的氧气乙醇的Stannyl自由基添加环化进行了平稳进行的，以提供转化为氨基辛醇的环状氨基醇。发现基本反应是通过最稳定的过渡态进行的，涉及至少1，3-甲基化应变。分别通过两个关键反应（分别为1、2-wittig重排和不对称羟基化）完成了亚二苯甲苯的形成。

项目成果

宮部豪人: "Asymmetric Synthesis of α-Amino Acids Based on Carbon Radical Addition to Glyoxylic Oxime Ether"J. Org. Chem.. 65. 176-185 (2000)

Goto Miyabe：“基于乙醛肟醚碳自由基加成的 α-氨基酸的不对称合成”J. Org. 65. 176-185 (2000)

内藤猛章: "Radical Cyclization of Oxime Ethers Derived from Monosaccharides Aiming at the Synthesis of Dysiherbaine and Related Stereoisomers"Heterocycles. 53. 2611-2615 (2000)

Takeaki Naito：“单糖衍生的肟醚的自由基环化旨在合成 Dysiherbaine 和相关立体体”杂环。 53. 2611-2615 (2000)

宮部 豪人: "Synthesis of aminocyclohexitol via carbon-carbon bond-forming radical cyclization of oxime ether"Chem. Pharm. Bull.. 51(1). 100-103 (2003)

Goto Miyabe：“通过肟醚的碳-碳键自由基环化合成氨基环己醇”，Chem.Bull.51(1)(2003)。

宮田興子: "Radical cyclization in heterocycle synthesis. Part 13.:Sulfanyl radical radical addtion-cyclization of oxime ethers and hydazone"Tetrahedron. 58. 4459-4479 (2002)

Koko Miyata：“杂环合成中的自由基环化。第 13 部分：肟醚和腙的磺基自由基加成环化”Tetrahedron 58。4459-4479 (2002)

宮部豪人: "Alkylative Amination of Aldehydes via Carbon-Carbon Bond Formation Based on Radical Addition to Carbon-Nitrogen Double Bond"Tetrahedron. 55. 11209-11218 (1999)

Goto Miyabe：“通过基于碳-氮双键的自由基加成的碳-碳键形成醛的烷基胺化”四面体。 55. 11209-11218 (1999)