On-DNA Synthesis of Arylhydrazones via Aryl Diazonium-Mediated Diazenylation
Abstract Arylhydrazones represent a privileged class of scaffolds with diverse biological activities that are widely utilized in medicinal chemistry. Here, we report a mild yet effective strategy for constructing arylhydrazones via the in situ generation of DNA-conjugated aryl diazonium intermediates, followed by subsequent coupling with a variety of active methylene compounds. This method features broad substrate scopes, good to excellent conversions for both DNA-conjugated arylamine and DNA-conjugated active methylene coupling partners, and good compatibility with the DNA-encoded library (DEL) workflow, significantly expanding the accessible chemical space for DEL-based drug discovery.
Authors
- Cai‐Guang Yang (ORCID: https://orcid.org/0000-0001-5778-4422)
- Yangfeng Li (ORCID: https://orcid.org/0000-0002-4780-6154)
- Ze Dong (ORCID: https://orcid.org/0000-0003-4876-415X)
- Gong Zhang (ORCID: https://orcid.org/0000-0002-6992-176X)
- Xiaoyu Li (ORCID: https://orcid.org/0000-0002-8907-6727)
- Xianfeng Li (ORCID: https://orcid.org/0000-0002-0000-8809)
- Zhongqi Shi
- Qiuyi Chen
- Qiang Li
Institutions
- Chongqing University (CN)
- Chinese Academy of Sciences (CN)
- Shanghai Institute of Materia Medica (CN)
- Chongqing Three Gorges Central Hospital (CN)
- University of Chinese Academy of Sciences (CN)
- Chongqing Three Gorges University (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2026-10-09
- DOI
- https://doi.org/10.1021/acs.orglett.6c03572
- Primary Topic
- Click Chemistry and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00