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.

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

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry and Czech Advanced Technology and Research Institute Palacky University and University Hospital in Olomouc 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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