Synthesis and Biological Profiling of Benzofuro‐Fused 7‐Deazapurine Nucleosides

Abstract

A series of benzofuro‐fused 7‐deazapurine (6H‐furo[2,3‐e]pyrimido[4,5‐b]indole) 2’‐deoxyribo‐ and ribonucleosides was designed and synthesized. The synthesis of key 10‐chloro‐6H‐furo[2,3‐e]pyrimido[4,5‐b]indole was based on the Negishi cross‐coupling of iodobenzofurane with zincated 4,6‐dichloropyrimidine followed by azidation and photochemical cyclization. Glycosylation of the heterocycle with either Hoffer’s chlorodeoxyribose or protected ribose followed by cross‐coupling or substitution reactions at position 10 gave the desired two sets of final nucleosides that showed moderate to weak cytostatic activity and interesting fluorescence properties.

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

“…Although the nucleosides 14c , 14e , and 14f are more potent against the CCRF-CEM line compared to their naphtho-fused analogs (6–8 vs 20–23 μM), their activities are still 2 orders of magnitude lower than their tricyclic thieno-, furo-, N -methylpyrrolo-, and pyrido-fused analogs. This is in agreement with our previous findings ,,, that nucleosides with tetracyclic nucleobases are already too bulky to be activated by phosphorylation and to interact with their biological target(s).…”

“…Samples were dissolved in DMSO (1 μL injection volume). Biological activity screening was performed as described previously. − ,− …”