Convergent synthesis of alpha-ketoamide inhibitors of Pin1.
Convergent synthesis of alpha-ketoamide inhibitors of Pin1.
复制标题
Pin1 的 α-酮酰胺抑制剂的聚合合成。
DOI：
10.1021/ol9027013
复制
发表时间：
2010
期刊：
影响因子：
5.2
通讯作者：
Etzkorn,FeliciaA
中科院分区：
文献类型：
--
作者：
Xu,GuoyanG;Etzkorn,FeliciaA
描述了Pin 1 α-酮酰胺抑制剂的收敛合成。丝氨酸的α-羟基原硫代酯衍生物直接与胺合成子反应。在HgO和HgCl_2的催化下，反应生成α-羟基酰胺。因此，水解和偶联结合在一个步骤中，产率为80%。合成了一种磷酸化的Ser-Pro α-酮酰胺类似物的两种非对映异构体。对于Pin 1肽基脯氨酰异构酶，100和200 μM的IC 50值令人惊讶地弱。
A convergent synthesis of α-ketoamide inhibitors of Pin1 is described. An α-hydroxyorthothioester derivative of Ser was reacted directly with an amine synthon. The reaction was catalyzed by HgO and HgCl2to form α-hydroxyamide. Thus, hydrolysis and coupling were combined in one step with 80% yield. Two diastereomers of a phospho-Ser-Pro α-ketoamide analogue were synthesized. The IC50values of 100 and 200 μM were surprisingly weak for Pin1 peptidyl prolyl isomerase.