APPROACH TO FUNCTION ELUCIDATION AND APPLICATION STUDY OF THE BIOACTIVE SUBSTANCES BY ORGANIC SYNTHESIS

有机合成生物活性物质的功能阐明及应用研究

• 批准号: 11660102
• 负责人: WATANABE Hidenori
• 金额: $ 1.98万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11660102/
• 关键词: FR901461; KAITOCEPHALIN; CELL CYCLE INHIBITOR; NEUROPROTECTIVE SUBSTANCE; STEREOSELECTIVE SYNTHESIS; 類縁体合成; 構造-活性相関; アセトフタリジン; プリュッシン

The total synthesis of FR9014614, a cell cycle inhibitor was accomplished from *-methyl intermediate, which possesses higher activity than the natural one. *-Biotinylated analog was also prepared from FR901464 and using this compound as a probe, isolation and identification of the binding protein and analysis of its function is in progress.By the total synthesis of kaitocephalin, a neuroprotective substance, it was found that the stereostructure had been misassigned. Comparison of spectral data of several stereoisomers and simplified analogs with those of the natural compound suggested a correct stereostructure. The revised structure was confirmed by the total synthesis. Bioassay of the synthetic stereoisomers and analogs gave interesting informations about the structure-activity relationships.

细胞周期抑制剂FR 9014614是以 *-甲基中间体为原料合成的，其活性高于天然产物。从FR 901464中还制备了 *-生物素化类似物，并以该化合物为探针，分离鉴定了结合蛋白，并对其功能进行了分析。几个立体异构体和简化的类似物与天然化合物的光谱数据的比较建议正确的立体结构。通过全合成证实了修正后的结构。对合成的立体异构体和类似物的生物测定提供了关于结构-活性关系的有趣信息。

项目成果

Hidenori Watanabe, Masayuki Okue: "The First Synthesis of kaitocephalin Based on the Structure Revision"Tetrahedron Letters. 43巻. 861-864 (2002)

Hidenori Watanabe，Masayuki Okue：“基于结构修正的kaitocephalin 的首次合成”Tetrahedron Letters 43. 861-864 (2002)。

Masayuki Okue: "A Concise Synthesis of (+)-Preussin"Tetrahedron. 57巻(印刷中). (2001)

Masayuki Okue：“(+)-普鲁士的简明综合”，第 57 卷（印刷中）。

Masato Horigome, Hidenori Watanabe: "A Synthesis of FR901464"Tetrahedron Letters. 42巻. 8207-8210 (2001)

Masato Horigome，Hidenori Watanabe：“FR901464 的综合”四面体信件 42 卷（2001 年）。

Masayuki Okue, Hidenori Watanabe, and Takeshi Kitahara: "A Concise Synthesis of (+)-Preussin"Tetrahedron. 57. 4107-4110 (2001)

Masayuki Okue、Hidenori Watanabe 和 Takeshi Kitahara：“( )-普鲁士”四面体的简明综合。

Hidenori Watanabe: "The Efficient Synthesis of Pironetins Employing the Useful Chiral Building Block, (1S,5S,6R)-5-hydroxybicyclo [4.1.0]heptan-2-one"Tetrahedron. 55. 9755-9776 (1999)

Hidenori Watanabe：“采用有用的手性构件（(1S,5S,6R)-5-羟基双环[4.1.0]庚-2-一”四面体有效合成 Pironetins。