Synthesis of Polycyclic Hetero-Fused 7-Deazapurine Heterocycles and Nucleosides through C–H Dibenzothiophenation and Negishi Coupling
Chao Yang, Lenka Poštová Slavětínská, Marianne Fleuti, Blanka Klepetářová, Michal Tichý, Soňa Gurská, Petr Pavliš, Petr Džubák, Marián Hajdúch, Michal Hocek
Abstract
-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.