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

0585794 - ÚOCHB 2025 RIV US eng J - Journal Article
Fleuti, Marianne - Sánchez Quirante, Tania - Poštová Slavětínská, Lenka - Tloušťová, Eva - Tichý, Michal - Gurská, S. - Džubák, P. - Hajdúch, M. - Hocek, Michal
Synthesis and Biological Profiling of Quinolino-Fused 7-Deazapurine Nucleosides.
ACS Omega. Roč. 9, č. 18 (2024), s. 20557-20570. ISSN 2470-1343. E-ISSN 2470-1343
R&D Projects: GA MŠMT LX22NPO5102; GA MŠMT(CZ) LM2023053
Research Infrastructure: CZ-OPENSCREEN IV - 90252
Institutional support: RVO:61388963
Keywords : center-dot-licl * enzymatic incorporation * analogs
Impact factor: 4.1, year: 2022
Method of publishing: Open access
https://doi.org/10.1021/acsomega.4c02031

A series of quinolino-fused 7-deazapurine (pyrimido[5′,4′:4,5]pyrrolo[3,2-f]quinoline) ribonucleosides were designed and synthesized. The synthesis of the key 11-chloro-pyrimido[5′,4′:4,5]pyrrolo[3,2-f]quinoline was based on the Negishi cross-coupling of iodoquinoline with zincated 4,6-dichloropyrimidine followed by azidation and thermal or photochemical cyclization. Vorbrüggen glycosylation of the tetracyclic heterocycle followed by cross-coupling or substitution reactions at position 11 gave the desired set of final nucleosides that showed moderate to weak cytostatic activity and fluorescent properties. The corresponding fused adenosine derivative was converted to the triphosphate and successfully incorporated to RNA using in vitro transcription with T7 RNA polymerase.
Permanent Link: https://hdl.handle.net/11104/0353484