Synthesis of Cyclic Amino Acids Aiming at Elucidation of Neurotransmission Mechanism

为了阐明与氨基酸有关的神经传递机制，我们开始开发一种适合于实际合成环状氨基酸的新型环化反应，这将成为神经递质机制研究的重要工具。因此，生态巯基加成-碳多键环化和锡基加成-羰基环化已被证明是有潜力的环状氨基酸的合成方法。巯基自由基加成-环化及其在环氨基酸合成中的应用对易得的肟醚进行巯基自由基加成-环化，得到邻接官能化的环状化合物，这些化合物可有效地转化为碳环和杂环氨基酸。采用新发现的噻基自由基加成-环化-消除反应，以一定量的噻吩为催化剂，实现了(-)-α-kainic酸的不对称合成。1,3-偶极环加成硝基酮及其在环氨基酸合成中的应用1,3-偶极环加成硝基酮与手性烯烃的结合及随后的环转化已成功地应用于合成叠氮酸，叠氮酸是大环内酯类氨基内酯、叠氮胺的组成部分，有望在中枢神经系统中发挥活性。锡基自由基加成-环化及其在环状氨基酸合成中的应用。我们开发了与羰基相连的肟醚的锡基自由基加成环化方法，并将其应用于环氨基酸和(-)-巴拉醇等相关化合物的合成。

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.