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Synthesis of Cyclic Amino Acids Aiming at Elucidation of Neurotransmission Mechanism

环状氨基酸的合成旨在阐明神经传递机制

基本信息

批准号：
09672293
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：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672293/
关键词：
neurotransmission mechanism Kainic acid amino acid radical thiophenol cyclization dipolar cycloaddition

项目摘要

Aiming at elucidation of neurotransmission mechanism involving amino acids, we started to develop a novel cyclization reactions suitable for the practical synthesis of cyclic amino acids which would be employed as crucial tools for the mechanistic study on neurotransmitters. Thus, ecological thiyl radical addition-cyclization of carbon multiple bonds and stannyl radical addition-cyclization of the carbonyl group have been proved to be potential synthetic method for the cyclic amino acids.1. Thiyl Radical Addition-Cyclization and its Application to the Synthesis of Cyclic Amino AcidsReadily available oxime ethers were subjected to thiyl radical addition-cyclization to give the adjacently functionalized cyclic compounds which were effectively converted into carbocyclic and heterocyclic amino acids. Asymmetric synthesis of (-)-α-kainic acid was achieved by applying newly found thiyl radical addition-cyclization-elimination reacting using a catalytic amount of thiophenol.2. 1,3-Dipolar Cycloaddition of Nitrone and its Application to the Synthesis of Cyclic Amino AcidsCombination of 1,3-dipolar cycloaddition of nitrones to chiral olefin and the following ring conversion were successfully applied the synthesis of azimic acid which is component of macrolide amino lactone, azimine, and expected to be active in central nervous system.3. Stannyl Radical Addition-Cyclization and its Application to the Synthesis of Cyclic Amino acids.We developed stannyl radical addition-cyclization of oxime ethers connected with the carbonyl groups and application to the synthesis of cyclic amino acids and the related compounds such as (-)-balanol.

为了阐明涉及氨基酸的神经传递机制，我们开始开发一种新的适合于实际合成环状氨基酸的环化反应，作为神经递质机理研究的重要工具。因此，生态硫自由基加成-碳多键环化和锡基自由基加成-羰基环化是合成环状氨基酸的潜在方法。硫基自由基加成-环化反应及其在环状氨基酸合成中的应用通过硫基自由基加成-环化反应得到具有邻位功能的环状化合物，有效地转化为碳环和杂环氨基酸。通过新发现的硫基自由基加成-环合-消除反应，在催化量的硫酚的作用下，实现了(-)-α-海人藻氨酸的不对称合成。硝酮的1，3-偶极环加成反应及其在环状氨基酸合成中的应用1，3-硝酮与手性烯烃的1，3-偶极环加成反应与随后的环转换反应相结合，成功地合成了大环内酯类氨基内酯的成分氮丙亚胺，该化合物有望在中枢神经系统发挥作用。锡基自由基加成-环化反应及其在环状氨基酸合成中的应用我们发展了与羰基相连的肟醚的锡基自由基加成-环化反应，并应用于环状氨基酸及其相关化合物(-)-巴拉诺的合成。