Greener synthesis of a potent proteolysis targeting chimera (PROTAC) degrader of indoleamine-2, 3-dioxygenase 1 (hDOI1)

FH-HES (Universities of Applied Sciences)

Authors

  • Emilie Buchs School of Engineering and Architecture of Fribourg, Department of Chemistry -, Institute of Chemical Technology, HES-SO University of Applied Sciences and Arts Western Switzerland, Boulevard de Pérolles, 80, CH-1700 Fribourg, Switzerland
  • Souvik Guha School of Engineering and Architecture of Fribourg, Department of Chemistry -, Institute of Chemical Technology, HES-SO University of Applied Sciences and Arts Western Switzerland, Boulevard de Pérolles, 80, CH-1700 Fribourg, Switzerland https://orcid.org/0000-0002-5257-1265
  • Subhabrata Sen Department of Chemistry, School of Natural Science, Shiv Nadar Institution of Eminence Deemed to be University, Dadri, Chithera, Gautam Buddha Nagar, UP 201314, India. https://orcid.org/0000-0002-4608-5498
  • Ludovic Gremaud School of Engineering and Architecture of Fribourg, Department of Chemistry -, Institute of Chemical Technology, HES-SO University of Applied Sciences and Arts Western Switzerland, Boulevard de Pérolles, 80, CH-1700 Fribourg, Switzerland https://orcid.org/0000-0002-0630-932X

DOI:

https://doi.org/10.2533/chimia.2025.665

Keywords:

Indoles, Photochemistry, Pomalidomide, PROTACS

Abstract

The synthesis of the potential indoleamine-2, 3-dioxygenase 1 (IDO1) degrader proteolysis-targeting chimeras (PROTAC) using sustainable reagents and technologies such as ionic liquids and photochemical couplings was investigated. The ligand to the protein of interest, an indole derivative, was synthesized successfully for three substrates bearing different substituents (NO2, (CF3)2 and H) over three steps with good to satisfactory results with overall yields ranging from 21 to 71%. However, the coupling with the ubiquitin ligase, pomalidomide, was unsuccessful due to the degradation of the reactive diazoketone functional group.

CHIMIA Vol. 79 No. 9 (2025): Green & Sustainable Chemistry: Trends and Outlooks

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Published

2025-09-10

Issue

Vol. 79 No. 9 (2025): Green & Sustainable Chemistry: Trends and Outlooks

Section

Columns, Conference Reports

License

Copyright (c) 2025 Swiss Chemical Society

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

How to Cite

[1]
E. Buchs, S. . Guha, S. Sen, L. Gremaud, Chimia 2025, 79, 665, DOI: 10.2533/chimia.2025.665.