Iron/Copper Co-Catalyzed Cross-Coupling Reaction for the Synthesis of 6‑Substituted 7‑Deazapurines and the Corresponding Nucleosides

• Published in: Journal of organic chemistry Vol. 85; no. 2; pp. 403 - 418
• Main Authors: Li, Qingfeng, Persoons, Leentje, Daelemans, Dirk, Herdewijn, Piet
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 17.01.2020; Amer Chemical Soc
• Subjects: aromatic compounds; Catalysis; catalytic activity; Cell Line, Tumor; cell lines; chemical structure; Chemistry; Chemistry, Organic; Copper - chemistry; cross-coupling reactions; cytotoxicity; Drug Screening Assays, Antitumor; Grignard reagents; Humans; iron; Iron - chemistry; neoplasm cells; neoplasms; organic chemistry; palladium; Physical Sciences; Purine Nucleosides - chemical synthesis; Purine Nucleosides - pharmacology; Purines - chemical synthesis; Purines - pharmacology; ribonucleosides; Science & Technology; IRON CATALYSIS; ALKENYL HALIDES; ANALOG; PYRROLOPYRIMIDINE NUCLEOSIDES; TUBERCIDIN; RIBONUCLEOSIDES; GLYCOSYLATION; GRIGNARD-REAGENTS
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/acs.joc.9b02414

An efficient access to 6-substituted 7-deazapurine and the corresponding nucleosides by coupling aryl or alkyl Grignard reagents and halogenated purine nucleosides in the presence of Fe­(acac)3/CuI is described. A series of 6-substituted 7-deazapurines and the corresponding nucleosides were obtained in medium to good yields. For the synthesis of modified nucleosides that will be the subject of biological testing, we propose to use iron-catalyzed instead of palladium-catalyzed reaction. The synthesized compounds were tested for their antiproliferative activity. The cytotoxicity study of compounds 11a–q shows that by modifying the 6-position of 7-deazapurine ribonucleosides, the compounds may become selective for certain cancer cell lines.