Synthesis of Polycyclic Hetero-Fused 7-Deazapurine Heterocycles and Nucleosides through C-H Dibenzothiophenation and Negishi Coupling.
J Am Chem Soc
; 144(42): 19437-19446, 2022 10 26.
Article
de En
| MEDLINE
| ID: mdl-36245092
ABSTRACT
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Ribonucléosides
/
Nucléosides
Langue:
En
Journal:
J Am Chem Soc
Année:
2022
Type de document:
Article
Pays d'affiliation:
République tchèque