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Simplifying Access to Targeted Protein Degraders via Nickel Electrocatalytic Cross-Coupling
Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, 92037, La Jolla, CA, United States.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Organic chemistry. Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, 92037, La Jolla, CA, United States.
Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, 92037, La Jolla, CA, United States.
Small Molecule Drug Discovery, Bristol Myers Squibb Research & Early Development, Route 206 & Province Line Road, 08543, Princeton, NJ, United States.
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2024 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 63, no 16, article id e202319856Article in journal (Refereed) Published
Abstract [en]

C−C linked glutarimide-containing structures with direct utility in the preparation of cereblon-based degraders (PROTACs, CELMoDs) can be assessed in a single step from inexpensive, commercial α-bromoglutarimide through a unique Brønsted-acid assisted Ni-electrocatalytic approach. The reaction tolerates a broad array of functional groups that are historically problematic and can be applied to the simplified synthesis of dozens of known compounds that have only been procured through laborious, wasteful, multi-step sequences. The reaction is scalable in both batch and flow and features a trivial procedure wherein the most time-consuming aspect of reaction setup is weighing out the starting materials.

Place, publisher, year, edition, pages
Wiley , 2024. Vol. 63, no 16, article id e202319856
Keywords [en]
Cross-Coupling, Electrochemistry, Nickel Catalysis, Proteins, Radicals
National Category
Organic Chemistry Biocatalysis and Enzyme Technology
Identifiers
URN: urn:nbn:se:kth:diva-366950DOI: 10.1002/anie.202319856ISI: 001179941400001PubMedID: 38354272Scopus ID: 2-s2.0-85187158789OAI: oai:DiVA.org:kth-366950DiVA, id: diva2:1983505
Note

QC 20250711

Available from: 2025-07-11 Created: 2025-07-11 Last updated: 2025-07-11Bibliographically approved

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Massaro, Luca

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