A General Strategy to Access Pharmaceutically Relevant Pyridines from Nitroarenes
Argha Saha1, Avishek Pan1, Devika Ghosh1
1Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India.
Angewandte Chemie (International Ed. in English)
|December 24, 2025
Summary
This study introduces a novel method to convert nitroarenes into pyridine heterocycles using an iron-porphyrin catalyst. This efficient process allows for selective carbon deletion, aiding drug design and molecular remodeling.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Catalysis
Background:
- Nitrogen-containing heterocycles are crucial in drug design for modulating molecular properties and bioactivity.
- Developing efficient synthetic routes to these scaffolds is vital for pharmaceutical development.
Purpose of the Study:
- To report a novel and efficient strategy for converting nitroarenes into pharmaceutically relevant pyridine heterocycles.
- To introduce a new nitrene-mediated transformation driven by a bio-inspired catalyst.
Main Methods:
- Utilized a bio-inspired iron-porphyrin catalyst as a singlet oxygen reservoir.
- Employed a nitrene-mediated transformation for C5-carbon deletion in a ring-editing cascade.
- Investigated the conversion of nitroarenes to aminopyridines.
Main Results:
- Achieved the first-time conversion of nitroarenes into pyridine heterocycles via selective C5-carbon deletion.
- Demonstrated a broad substrate scope with high regioselectivity under mild conditions.
- Successfully applied the method for late-stage functionalization of nimesulide derivatives, improving molecular docking and binding profiles.
Conclusions:
- The developed catalytic strategy offers a powerful new retrosynthetic logic for heterocycle construction.
- This method provides a practical and step-economical route to bioactive pyridine scaffolds from nitroarenes.
- The modular platform facilitates the synthesis of drug-like scaffolds with potential pharmaceutical applications.
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