Investigating sequence space:: How important is the spatial arrangement of functional groups in the asymmetric aldol reaction catalyst H-Pro-Pro-Asp-NH2?
Investigating sequence space:: How important is the spatial arrangement of functional groups in the asymmetric aldol reaction catalyst H-Pro-Pro-Asp-NH2?
复制标题
DOI：
10.1002/adsc.200800053
复制
发表时间：
2008-05-01
影响因子：
5.4
通讯作者：
Wennemers, Helma
中科院分区：
文献类型：
--
作者：
Revell, Jefferson D.;Wennemers, Helma
H-Pro-Pro-Asp-NH 2 1是不对称羟醛反应的多功能催化剂。在催化剂结构中，N-末端仲胺和羧酸对于有效催化都是至关重要的。在这里，这两个功能组对彼此的安排的重要性进行了审查。制备了几种H-Pro-Pro-Asp-NH 2类似物，其中仲胺和羧酸占据不同的位置。对它们的催化性能的评价表明，这两个官能团的位置对于有效的催化是非常关键的。即使是看似很小的结构修饰，例如，一个亚甲基或多或少，可以改变催化性能显着。结果表明，在合理设计的肽催化剂和催化剂发现的组合智能筛选方法的价值的困难。
H-Pro-Pro-Asp-NH2 1 is a versatile catalyst for asymmetric aldol reactions. Within the catalyst structure, both the N-terminal secondary amine and the carboxylic acid are crucial for efficient catalysis. Here, the importance of the arrangement of these two functional groups towards each other was examined. Several analogues of H-Pro-Pro-Asp-NH2 were prepared in which the secondary amine and the carboxylic acid occupy different positions. Evaluation of their catalytic properties revealed that the placement of these two functional groups is highly critical for efficient catalysis. Even seemingly small structural modifications, for example, one methylene group more or less, can modify the catalytic properties significantly. The results demonstrate the difficulty in rationally designing a peptidic catalyst and the value of combinatorial smart screening methods for catalyst discovery.