Two isomeric series of benzothieno-fused 7-deazapurine (benzo[4',5']thieno[3',2':4,5]- and benzo[4',5']thieno[2',3':4,5]pyrrolo[2,3-d]pyrimidine) ribonucleosides were designed and synthesized. Key steps of the synthesis included the Negishi coupling of zincated dichloropyrimidine with 2- or 3-iodobenzothiophene followed by azidation, thermal or photochemical cyclization, glycosylation, and final functionalization at position 6 through cross-couplings or nucleophilic substitutions. Deprotection gave the final nucleosides, some of which showed moderate cytotoxic and antiviral activity. Most of the free nucleosides showed moderate to strong fluorescence with emission maxima of 362-554 nm. 2'-Deoxyribonucleoside and its 5'-O-triphosphate were also prepared from benzothieno-fused 7-deazaadenine derivative, and the triphosphate was a good substrate for KOD XL DNA polymerase in primer extension synthesis of modified DNA which exerted a weak fluorescence which was slightly enhanced in double-stranded DNA as compared to single-stranded oligonucleotides.

Department of Organic Chemistry Faculty of Science Charles University Prague Hlavova 8 CZ 12843 Prague 2 Czech Republic

Institute of Molecular and Translational Medicine Palacky University and University Hospital in Olomouc Faculty of Medicine and Dentistry Hněvotínská 5 CZ 77515 Olomouc Czech Republic

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo nam 2 CZ 16610 Prague 6 Czech Republic

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Synthesis and Biological Profiling of Quinolino-Fused 7-Deazapurine Nucleosides

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