Synthesis, Photophysical Properties, and Biological Profiling of Benzothieno-Fused 7‑Deazapurine Ribonucleosides

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.