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

0563594 - ÚOCHB 2023 RIV US eng J - Journal Article
Yang, Chao - Poštová Slavětínská, Lenka - Fleuti, Marianne - Klepetářová, Blanka - Tichý, Michal - Gurská, S. - Pavliš, P. - Džubák, P. - Hajdúch, M. - Hocek, Michal
Synthesis of Polycyclic Hetero-Fused 7-Deazapurine Heterocycles and Nucleosides through C-H Dibenzothiophenation and Negishi Coupling.
Journal of the American Chemical Society. Roč. 144, č. 42 (2022), s. 19437-19446. ISSN 0002-7863. E-ISSN 1520-5126
R&D Projects: GA MŠMT LX22NPO5102; GA MŠMT(CZ) LM2018133
Research Infrastructure: CZ-OPENSCREEN III - 90130
Institutional support: RVO:61388963
Keywords : enzymatic incorporation * antiviral activity * analogs
OECD category: Biochemistry and molecular biology
Impact factor: 15, year: 2022
Method of publishing: Open access
https://doi.org/10.1021/jacs.2c07517

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.
Permanent Link: https://hdl.handle.net/11104/0335502