基于d-脯氨酰胺的不对称合成及消旋研究

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1、摘要脯氨酞胺是一种重要的五元环状氨基酸衍生物。一脯氨酞胺一作为一种重要的光学活性毗咯衍生物，无论是用作拆分剂和手性试剂，或作为手性中间体合成某些手性药物，其在各种不对称合成反应中都显示出了优良的不对称源性能。如在合成抗肿瘤药物铂化合物、促，甲状腺释放剂精神安定药、瑞莫比利等药物中，都发挥了重要的作用。合成一脯氨酞胺主要采用手性源技术合成，即以一脯氨酸一为原料来合成。由于一难以从自然产品中大量获得，虽可通过化学拆分的方法制备，但由于拆分方法本身的限制，其最高理论收率只能达到，因此价格昂贵。本文从经济角度出发，运用不对称转换的方法，以一

2、为起始原料，以酒石酸作拆分剂，合成一。然后通过上保护基，氨化和脱保护基等反应最后得到一脯氨酞胺。并对其合成工艺进行了优化。另外，文章为了有可比性，还运用了两种保护基氯甲酸节酷和对甲基苯磺酞氯来保护氨基，并从最后合成结果来讨论这两种保护基的可行性。由于在合成过程中，不可避免的触及不对称中心，发生消旋使产率下降甚至，一、、得不到产物因此本文还研究了脯氨酞胺在不同温度值反应时间下对它的消旋的影响和脱梭机理，这对以后的工业化生产有着极其重要的意义。一一关键词脯氨酸卜脯氨酸脯氨酞胺氯甲酸节酷对甲基苯磺酞氯消旋不对称合成一巾，一以，，只一，一几

3、，杭以一一怕一，一，一，一，以一，，一一·闭，目录第一章概述··················································……概述························································……脯氨酸和脯氨酞胺的物理化学性质··························……·····································””””第二章文献综述……··································

4、“”’立体化学中的概念……”立体异构体···············································……对映体······················，·····························……非对映异构体·············································……光学纯度··················································……比旋光度·······························

5、···················……对映体过量···············································……··································‘立体选向百分率……””””消旋······················································……消旋度························……，····················……拆分··································

6、···················……消旋方法论述···············································……热消旋·························……，···················……碱催化消旋···············································……酶催化消旋···············································……氧化还原消旋···························

7、··················……酸催化消旋···············································……消旋方法选择·············································……构型转换方法论述··········································……瓦尔登转化···············································……拆分分离法·······························

8、················……动力学拆分···············································……不对称转换········································