Pin1 的α-酮酰胺抑制剂的汇聚合成。
Convergent synthesis of alpha-ketoamide inhibitors of Pin1.
机构信息
Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, USA.
出版信息
Org Lett. 2010 Feb 19;12(4):696-9. doi: 10.1021/ol9027013.
Abstract
A convergent synthesis of alpha-ketoamide inhibitors of Pin1 is described. An alpha-hydroxyorthothioester derivative of Ser was reacted directly with an amine synthon. The reaction was catalyzed by HgO and HgCl(2) to form alpha-hydroxyamide. Thus, hydrolysis and coupling were combined in one step with 80% yield. Two diastereomers of a phospho-Ser-Pro alpha-ketoamide analogue were synthesized. The IC(50) values of 100 and 200 microM were surprisingly weak for Pin1 peptidyl prolyl isomerase.
摘要
描述了 Pin1 的α-酮酰胺抑制剂的汇聚合成。Ser 的α-羟基邻硫代酯衍生物与胺合成子直接反应。反应由 HgO 和 HgCl(2) 催化形成α-羟基酰胺。因此，水解和偶联在一步中进行，收率为 80%。磷酸丝氨酸脯氨酰α-酮酰胺类似物的两个非对映异构体被合成。Pin1 肽基脯氨酰异构酶的 IC(50) 值出人意料地低，为 100 和 200 μM。
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