Development and mechanistic study of novel anti-Alzheimer's disease drugs based on physiologically active fatty acid

基于生理活性脂肪酸的新型抗阿尔茨海默病药物的开发及作用机制研究

• 批准号: 20890266
• 负责人: SHIMIZU Tadashi
• 金额: $ 2.11万
• 依托单位: Hyogo University of Health Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (Start-up)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20890266/
• 关键词: 認知症治療剤; 生理活性脂肪酸; 光学分割; 光学活性誘導体; シクロプロパン; DCP-LA

We have already reported linoleic acid analogues without unstable cis-double bonds, called DCP-LA, which induced LTP-like long-lasting facilitation of hippocampal neurotransmission in both in vitro and in vivo systems. However, DCP-LA was four stereo-isomer mixtures, the determination of the most active isomer have been remained. In this reserch, we have developed synthetic route for the preparation of all of the four isomers of enantiomerically pure DCP-LA employing lipase-mediated resolution method, and found the most active stereoisomers.

我们已经报道了没有不稳定顺式双键的亚油酸类似物，称为 DCP-LA，它在体外和体内系统中诱导海马神经传递的 LTP 样持久促进。但DCP-LA是四种立体异构体的混合物，其中活性最强的异构体的测定仍有待确定。在本研究中，我们开发了采用脂肪酶介导的拆分方法制备对映体纯的DCP-LA的所有四种异构体的合成路线，并发现了最活跃的立体异构体。

项目成果

Asymmetric synthesis of isobenzofuranone derivatives and their unique character as protein kinase Cα(PKCα)

异苯并呋喃酮衍生物的不对称合成及其作为蛋白激酶Cα(PKCα)的独特特性

• 发表时间: 2009
• 期刊: Tetarahedron Letters 50
• 作者: G. Hirai;Y. Ogoshi;M. Ohkubo;Y. Tamura;T. Watanabe;T. Shimizu;M. Sodeoka;長環;Go Hirai
• 通讯作者: Go Hirai

Asymmetric synthesis of isobenzo furanone derivatives and their unique character as protein kinase Cα(PKCα).

异苯并呋喃酮衍生物的不对称合成及其作为蛋白激酶Cα(PKCα)的独特特性。

• 发表时间: 2009
• 期刊: Teterahedron Lett. 50
• 作者: G. Hirai;Y. Ogoshi;M. Ohkubo;Y. Tamura;T. Watanabe;T. Shimizu;M. Sodeoka
• 通讯作者: M. Sodeoka