Development of DNA-Compatible Suzuki-Miyaura Reaction in Aqueous Media

• Published in: Bioconjugate chemistry Vol. 29; no. 11; pp. 3841 - 3846
• Main Authors: Li, Jian-Yuan, Huang, Hongbing
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21.11.2018
• Subjects: Aqueous solutions; Aromatic compounds; Biocompatibility; Boronic Acids - chemical synthesis; Boronic Acids - chemistry; Catalysis; Chemical reactions; Coding; Compatibility; Coupling (molecular); Deoxyribonucleic acid; DNA; DNA - chemical synthesis; DNA - chemistry; DNA probes; Drug development; Esters; Esters - chemical synthesis; Esters - chemistry; Halides; Hydrocarbons, Aromatic - chemical synthesis; Hydrocarbons, Aromatic - chemistry; Hydrocarbons, Halogenated - chemical synthesis; Hydrocarbons, Halogenated - chemistry; Molecules; Organic chemistry; Palladium - chemistry; Small Molecule Libraries - chemical synthesis; Small Molecule Libraries - chemistry; Water - chemistry
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/acs.bioconjchem.8b00676

DNA-encoded chemical libraries (DELs) are a cost-effective technology for the discovery of novel chemical probes and drug candidates. A major limiting factor in assembling productive DELs is the availability of DNA-compatible chemical reactions in aqueous media. In an effort to increase the chemical accessibility and structural diversity of small molecules displayed by DELs, we developed a robust Suzuki-Miyaura reaction protocol that is compatible with the DNA structures. By employing a water-soluble Pd-precatalyst, we developed conditions that allow efficient coupling of DNA-linked aryl halides with a wide variety of boronic acids/esters including heteroaryl boronates.