オキサソール環の構築、開裂反応を基盤とする生理活性物質の合成研究

基于恶唑环的构建和裂解反应合成生理活性物质的研究

• 批准号: 62570948
• 负责人: HAMADA Yasumasa
• 金额: $ 1.28万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570948/
• 关键词: 4-Alkoxycarbonyloxazole; Antiulcer; AI-77-B; Dihydroisocoumarin; Hydroxy directed hydrogenation; 抗潰瘍性物質; オキサゾール; AIー77ーB; A1-77-B; C-アシル化反応; 隣接水酸基関与接触還元

We have already disclosed that 4-alkoxycarbonyloxazoles can be efficiently prepared by use of diphenyl phosphorazidate from carboxylic acid and alkyl isocyanoacetate. 4-Alkoxycarbonyloxazoles can be utilized as -hydroxy- -amino acid synthons. As an application of the oxazole synthesis, a synthesis of AI-77-B, a gastroprotective substance isolated from Bacillus pumilus AI-77, has been investgated by a convergent approach involving the two key fragments, the dihydroisocoumarin part and the hydroxy amino acid one. The dihydroisocoumarin part was prepared from the 6-methylsalicylic acid derivative and N-protected leucinal in one step. The hydroxy amino acid moiety was stereoselectively prepared via the corresponding oxazole from the glyceric acid derivative and ethyl isocyanoacetate. Alternatively, the hydroxy amino acid was constructed from ethyl D-pyroglutamate in a stereoselective manner. After proper deprotection of each part, coupling of the two key fragment was carried out by use of diethyl phosphorocyanidate to give the AI-77-B derivative with the nitrile function. final transformation of the nitrile part to the carboxylic acid one furnished AI-77-B which was identical with the natural product.

我们已经公开了用磷酸二苯酯由羧酸和烷基异氰乙酸酯有效地制备4-烷氧羰基氯唑。4-烷氧羰基氯唑可用作-羟基-氨基酸合子。作为恶唑合成的一个应用，我们研究了从矮芽孢杆菌AI-77中分离得到的胃保护物质AI-77- b的合成，采用了包括二氢异香豆素部分和羟基氨基酸部分两个关键片段的聚合方法。以6-甲基水杨酸衍生物和n -保护白蜡为原料一步制得二氢异香豆素部分。以丙三酸衍生物和异氰乙酸乙酯为原料，通过相应的恶唑立体选择性制备了羟基氨基酸部分。另外，羟基氨基酸以立体选择的方式由d -焦谷氨酸乙酯构建。对各部分进行适当的脱保护后，用磷酸氰酸二乙酯偶联两个关键片段，得到具有腈功能的AI-77-B衍生物。腈部分最终转化为羧酸部分，提供了与天然产物相同的AI-77-B。

项目成果

Takayuki Shioiri;Yasumasa Hamada: "Exploitation of New Synthetic Reagents and Their Application to the Total Synthesis of Biologically Active Natural Products" YAKUGAKU ZASSHI. 108. 1115-1128 (1988)

Takayuki Shioiri；Yasumasa Hamada：“新型合成试剂的开发及其在生物活性天然产物全合成中的应用”YAKUGAKU ZASSSHI。

T.Shioiri and Y.Hamada: Heterocycles. 27. 1035-1050 (1988)

T.Shioiri 和 Y.Hamada：杂环。

Y.Hamada;A.Kawai;Y.Kohno;O.Hara;T.Shioiri: J.Am.Chem.Soc.111. 1524-1525 (1989)

Y.Hamada；A.Kawai；Y.Kohno；O.Hara；T.Shioiri：J.Am.Chem.Soc.111。

A.Kawai;O.Hara;Y.Hamada;T.Shioiri: "STEREOSELECTIVE SYNTHESIS OF THE HYDROXY AMINO ACID MOIETY OF AI-77-B,A GASTROPROTECTIVE SUBSTANCE FROM Bacillus pumilus AI-77" Tetrahedron Lett.29. 6331-6334 (1988)

A.Kawai;O.Hara;Y.Hamada;T.Shioiri：“AI-77-B 的羟基氨基酸部分的立体选择性合成，一种来自短小芽孢杆菌 AI-77 的胃保护物质”四面体 Lett.29。

Y.Hamada;A.Kawai;Y.Kohno;O.Hara;T.Shioiri: "STEREOSELECTIVE TOTAL SYNTHESIS OF AI-77-B,A GASTROPROTECTIVE SUBSTANCE FROM Bacillus pumilus AI-77" J. Am. Chem. Soc.111. 1524-1525 (1989)

Y.Hamada;A.Kawai;Y.Kohno;O.Hara;T.Shioiri：“AI-77-B 的立体选择性全合成，一种来自短小芽孢杆菌 AI-77 的胃保护物质”J. Am。