Oxalyl Boronates Enable Modular Synthesis of Bioactive Imidazoles

Described herein is the preparation of oxalyl boronate building blocks and their application for the construction of heterocycles. The oxalyl unit, readily accessible through commercially available starting materials, enables a modular approach for the synthesis of imidazoles. A variety of aromatic,...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2017-05, Vol.56 (22), p.6264-6267
Main Authors: Lee, C. Frank, Holownia, Aleksandra, Bennett, James M., Elkins, Jonathan M., St. Denis, Jeffrey D., Adachi, Shinya, Yudin, Andrei K.
Format: Article
Language:English
Subjects:
Accessibility
Biocompatibility
biological activity
Biomedical materials
boron
Construction
Cross coupling
heterocycles
Imidazole
Inhibitors
Kinases
Palladium
Protein kinase
Scaffolds
Surgical implants
Synthesis
synthetic methods
Threonine
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Summary:Described herein is the preparation of oxalyl boronate building blocks and their application for the construction of heterocycles. The oxalyl unit, readily accessible through commercially available starting materials, enables a modular approach for the synthesis of imidazoles. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium‐catalyzed cross‐coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine‐protein kinase STK10 were synthesized. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium‐catalyzed cross‐coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine‐protein kinase STK10 were synthesized.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201611006