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

Abstract

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. Vorbruggen 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.