Development of Efficient Synthetic Method for Unnatural Amino Acids and Peptides and Its Application

在订购用吡咯烷衍生物将这种非自然氨基酸和肽纳入这类氨基酸的合成方法时，我们研究了血清衍生物的α-烷基化和β-替换反应以及随后的结果已经获得.1）氨基酯类的非对称α-烷基化成功地通过使用吡咯烷衍生物在C-3和/或chiral ansa-structure中实现了手性离子体链。增加活性α， α-dialkyl amino esters的增加。反应的立体电被发现依赖于金属离子的种类：手性环境是由金属离子与离子侧链协调的特别构造的。关于这种反应对肽、立体选择性和N-末端选择性α-排列的应用，已完成肽。用直接修改的非自然肽合成方法是一种新颖的方法。2）在C-3上有乙氧基衍生物组和C-5上的咪唑侧链发现了可催化β-替代SerO-碳酸酯的反应，用硫给予各种S-substituted Cys derivatives in the presence of Li-D1+-D1。肽在N-终端位置上也成功地转换为肽在N-终端位置上有S-替代的Cys在N-终端位置上也是。The β-replacement reaction with a carbon nucleophile such as nitroacetate also took place in the presence of Li-D1 + Li-D1 and Zn-I-D12+ Li-D1 by pyridoxal derivatives having a methylthio group at C-2.我们正在研究这些反应的应用程序到固体阶段反应，其中将是伟大的使用和versatile particularly on应用程序到构建肽库。

In order to establish the synthetic method for unnatural amino acids and peptides containing such amino acids by employing pyridoxal derivatives, we studied α-alkylation and β-replacement reaction of Ser derivatives and the following results were obtained.1) Asymmetric α-alkylation of amino esters were successfully achieved by employing pyridoxal derivatives having a chiral ionophore side chain at C-3 and/or a chiral ansa-structure, giving rise to optically active α, α-dialkyl amino esters. The stereoselectivity of the reaction was found to depend on the kind of metal ion : the chiral environment is specifically constructed by coordination of the metal ion with the ionophore side chain. On application of this reaction to peptides, stereoselective and N-terminal selective α-alkylation of peptides was accomplished, being a novel method for the synthesis of unnatural peptides by direct modification.2) Pyridoxal derivatives having an ethoxyethoxy group at C-3 and an imidazole side chain at C-5 was found to catalyze β-replacement reaction of Ser O-carbonate with thiols to give various S-substituted Cys derivatives in the presence of LiィイD1+ィエD1. Peptides having Ser O-carbonate at the N-terminal position were also successfully converted to the peptides having S-substituted Cys at the N-terminal position by the same reaction. The β-replacement reaction with a carbon nucleophile such as nitroacetate also took place in the presence of LiィイD1+ィエD1 and ZnィイD12+ィエD1 by using pyridoxal derivatives having a methylthio group at C-2.We are studying the application of these reactions to solid-phase reactions, which would be of great use and versatile particularly on application to construction of peptides library.