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

0531532 - ÚOCHB 2021 RIV US eng J - Journal Article
Yang, Chao - Pohl, Radek - Tichý, Michal - Gurská, S. - Pavliš, P. - Džubák, P. - Hajdúch, M. - Hocek, Michal
Synthesis, Photophysical Properties, and Biological Profiling of Benzothieno-Fused 7-Deazapurine Ribonucleosides.
Journal of Organic Chemistry. Roč. 85, č. 12 (2020), s. 8085-8101. ISSN 0022-3263. E-ISSN 1520-6904
R&D Projects: GA ČR(CZ) GA19-08124S; GA MZd(CZ) NV15-31984A; GA MŠMT(CZ) LM2015064
Institutional support: RVO:61388963
Keywords : nucleoside * inhibitors * antitumor
OECD category: Organic chemistry
Impact factor: 4.354, year: 2020
Method of publishing: Limited access
https://doi.org/10.1021/acs.joc.0c00927

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
Permanent Link: http://hdl.handle.net/11104/0310168