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Synthesis of Polycyclic Hetero-Fused 7-Deazapurine Heterocycles and Nucleosides through C–H Dibenzothiophenation and Negishi Coupling

[Image: see text] A new approach for synthesizing polycyclic heterofused 7-deazapurine heterocycles and the corresponding nucleosides was developed based on C–H functionalization of diverse (hetero)aromatics with dibenzothiophene-S-oxide followed by the Negishi cross-cooupling with bis(4,6-dichlorop...

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Detalles Bibliográficos
Autores principales: Yang, Chao, Slavětínská, Lenka Poštová, Fleuti, Marianne, Klepetářová, Blanka, Tichý, Michal, Gurská, Soňa, Pavliš, Petr, Džubák, Petr, Hajdúch, Marián, Hocek, Michal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9619403/
https://www.ncbi.nlm.nih.gov/pubmed/36245092
http://dx.doi.org/10.1021/jacs.2c07517
Descripción
Sumario:[Image: see text] A new approach for synthesizing polycyclic heterofused 7-deazapurine heterocycles and the corresponding nucleosides was developed based on C–H functionalization of diverse (hetero)aromatics with dibenzothiophene-S-oxide followed by the Negishi cross-cooupling with bis(4,6-dichloropyrimidin-5-yl)zinc. This cross-coupling afforded a series of (het)aryl-pyrimidines that were converted to fused deazapurine heterocycles through azidation and thermal cyclization. The fused heterocycles were glycosylated to the corresponding 2′-deoxy- and ribonucleosides, and a series of derivatives were prepared by nucleophilic substitutions at position 4. Four series of new polycyclic thieno-fused 7-deazapurine nucleosides were synthesized using this strategy. Most of the deoxyribonucleosides showed good cytotoxic activity, especially for the CCRF-CEM cell line. Phenyl- and thienyl-substituted thieno-fused 7-deazapurine nucleosides were fluorescent, and the former one was converted to 2′-deoxyribonucleoside triphosphate for enzymatic synthesis of labeled oligonucleotides.