Convergent synthesis of alpha-ketoamide inhibitors of Pin1.

Organic Letters
Guoyan G Xu, Felicia A Etzkorn

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.

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Citations

Jun 11, 2014·European Journal of Medicinal Chemistry·Wei AngYuquan Wei
Feb 18, 2016·Chemical Reviews·Carmela De RisiVinicio Zanirato
Jun 28, 2016·The Journal of Organic Chemistry·Yogesh KumarAmit Kumar
Nov 29, 2017·Organic & Biomolecular Chemistry·Xin LiuLong-Wu Ye
Aug 15, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Takatsugu MurataIsamu Shiina
Oct 3, 2018·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Shaista Sultan, Bhahwal Ali Shah
Jul 12, 2014·Chemical Communications : Chem Comm·Ramesh DeshidiBhahwal Ali Shah
Oct 15, 2013·Biochemistry·Ana Y Mercedes-CamachoFelicia A Etzkorn

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