Synthesis and Conformational Analysis of Amino Acids and Oligopeptides Labeled with Stable Isotopes

为了提高核磁共振蛋白质结构测定的效率，研究了立体选择性稳定的同位素标记氨基酸的简便大规模合成方法。本工作开发了一种合成八种标记氨基酸的关键中间体--不饱和焦谷氨醇衍生物的新方法，并实现了氢化脯氨酸和谷氨酸的克级合成。利用得到的脯氨酸制备了一些二肽，并对其进行了系统构象分析。借助于选择性的氚标记，可以用简单的1D核磁共振波谱来监测脯氨酸环的皱缩。

Facile and large-scale synthesis of stereoselectively stable isotope-labeled amino acids, which can promote the efficiency of NMR protein structure determination, was investigated. In this work, a novel synthetic method for unsaturated pyroglutaminol derivatives, key intermediates for eight kinds of labeled amino acids, has been developed and gram-scale syntheses of deuterated prolines and glutamic acids were achieved. Using the obtained proline, some dipeptides were prepared and a systematic conformational analysis was carried out. With the help of selective deuterium-labeling, it becomes feasible to monitor the proline ring puckering by means of simple 1D NMR spectroscopy.