Inverse-Electron-Demand Diels-Alder Reactions for the Synthesis of Pyridazines on DNA

Hailong Li; Zhen Sun; Wenting Wu; Xuan Wang; Mingqiang Zhang; Xiaojie Lu; Wenge Zhong; Dongcheng Dai

doi:10.1021/acs.orglett.8b03114

Inverse-Electron-Demand Diels-Alder Reactions for the Synthesis of Pyridazines on DNA

Org Lett. 2018 Nov 16;20(22):7186-7191. doi: 10.1021/acs.orglett.8b03114. Epub 2018 Oct 26.

Authors

Hailong Li¹, Zhen Sun¹, Wenting Wu¹, Xuan Wang^{1

2}, Mingqiang Zhang¹, Xiaojie Lu², Wenge Zhong¹, Dongcheng Dai¹

Affiliations

¹ Department of Discovery Modalities , Amgen Asia R&D Center, Amgen Research , 4560 Jinke Road , Pudong, Shanghai 201210 , P. R. China.
² State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica , Chinese Academy of Science , 501 Haike Road, Zhang Jiang Hi-Tech Park , Pudong, Shanghai 201203 , P. R. China.

PMID: 30365326
DOI: 10.1021/acs.orglett.8b03114

Abstract

The synthesis of pyridazines on DNA has been developed on the basis of inverse-electron-demand Diels-Alder (IEDDA) reactions of 1,2,4,5-tetrazines. The broad substrate scope is explored. Functionalized pyridazine products are selected for subsequent DNA-compatible Suzuki-Miyaura coupling, acylation, and S_NAr substitution reactions, demonstrating the feasibility and versatility of IEDDA reactions for DNA-encoded library synthesis.

MeSH terms

Acylation
Catalysis
Cycloaddition Reaction* / methods
DNA / chemistry*
Electrons
Heterocyclic Compounds, 1-Ring / chemistry*
Molecular Structure
Pyridazines / chemical synthesis*
Pyridazines / chemistry

Substances

Heterocyclic Compounds, 1-Ring
Pyridazines
DNA