Synthesis of Cyclic Amino Acids Aiming at Elucidation of Neurotransmission Mechanism

为了阐明氨基酸的神经传递机制，我们开始开发一种新的环化反应，适合于实际合成环状氨基酸，这将被用作神经递质机制研究的重要工具。因此，生态硫酰基自由基加成-碳重键环化和甲锡酰基自由基加成-羰基环化被证明是合成环状氨基酸的潜在方法.巯基加成-环化反应及其在环状氨基酸合成中的应用利用现成的肟醚进行巯基加成-环化反应，得到相邻官能团的环状化合物，有效地将其转化为碳环和杂环氨基酸。利用新发现的巯基加成-环化-消除反应，在催化量的硫酚作用下，实现了（-）-α-红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氨基酸合成中的应用将硝酮与手性烯烃的1，3-偶极环加成反应与随后的环转化反应相结合，成功地应用于大环内酯氨基内酯氮杂亚胺的组成成分氮杂亚胺酸的合成中，该化合物具有中枢神经系统活性.锡自由基加成-环化反应及其在环状氨基酸合成中的应用我们研究了与羰基相连的肟醚的锡自由基加成-环化反应及其在合成环状氨基酸及其相关化合物如（-）-巴诺醇中的应用。

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.