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

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2024 May 13

PMID 38737052

Authors

Marianne Fleuti

Tania Sanchez-Quirante

Lenka Postova Slavetinska

Eva Tloustova

Michal Tichy

Sona Gurska

Petr Dzubak

Marian Hajduch

Michal Hocek

Affiliations

Soon will be listed here.

Abstract

A series of quinolino-fused 7-deazapurine (pyrimido[5',4':4,5]pyrrolo[3,2-]quinoline) ribonucleosides were designed and synthesized. The synthesis of the key 11-chloro-pyrimido[5',4':4,5]pyrrolo[3,2-]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 transcription with T7 RNA polymerase.

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