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Synthesis 2020; 52(17): 2521-2527
DOI: 10.1055/s-0040-1707400
psp
© Georg Thieme Verlag Stuttgart · New York

A Facile Synthesis of Ligands for the von Hippel–Lindau E3 Ligase

Christian Steinebach 
a   Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany   eMail: guetschow@uni-bonn.de
,
Sabine Anna Voell
a   Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany   eMail: guetschow@uni-bonn.de
,
Lan Phuong Vu
a   Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany   eMail: guetschow@uni-bonn.de
,
Aleša Bricelj
b   Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia
,
Izidor Sosič 
b   Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia
,
Gregor Schnakenburg
c   Institute of Inorganic Chemistry, University of Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany
,
Michael Gütschow  ∗
a   Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany   eMail: guetschow@uni-bonn.de
› Institutsangaben
I.S. acknowledges funding by the Javna Agencija za Raziskovalno Dejavnost RS [Slovenian Research Agency (ARRS)] through research core funding No. P1-0208.
Weitere Informationen

Publikationsverlauf

Received: 05. März 2020

Accepted after revision: 06. Mai 2020

Publikationsdatum:
27. Mai 2020 (online)

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Abstract

The proteolysis-targeting chimeras (PROTACs) have become an integral part of different stages of drug discovery. This growing field, therefore, benefits from advancements in all segments of the design of these compounds. Herein, an efficient and optimized synthetic protocol to various von Hippel-Lindau (VHL) ligands is presented, which enables easy access to multigram quantities of these essential PROTAC building blocks. Moreover, the elaborated synthesis represents a straightforward approach to further explore the chemical space of VHL ligands.

Key words

PROTACs - protein degradation - von Hippel–Lindau - VHL - E3 ligase - reductive amination - protecting group

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707400.
  • Supporting Information
 

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