Synthesis of Fluorescent C-C Bonded Triazole-Purine Conjugates

Abstract

A design toward C-C bonded 2,6-bis(1H-1,2,3-triazol-4-yl)-9H-purine and 2-piperidinyl-6-(1H-1,2,3-triazol-4-yl)-9H-purine derivatives was established using the combination of Mitsunobu, Sonogashira, copper (I) catalyzed azide-alkyne cycloaddition, and S_NAr reactions. 11 examples of 2,6-bistriazolylpurine and 14 examples of 2-piperidinyl-6-triazolylpurine intermediates were obtained, in 38-86% and 41-89% yields, respectively. Obtained triazole-purine conjugates expressed good fluorescent properties which were studied in the solution and in the thin layer film for the first time. Quantum yields reached up to 49% in DMSO for bistriazolylpurines and up to 81% in DCM and up to 95% in DMSO for monotriazolylpurines. Performed biological studies in mouse embryo fibroblast, human keratinocyte, and transgenic adenocarcinoma of the mouse prostate cell lines showed that most of obtained triazole-purine conjugates are not cytotoxic. The 50% cytotoxic concentration of the tested derivatives was in the range from 59.6 to 1528.7 µM.

Keywords: CuAAC; Fluorescence; Fluorescent purines; Sonogashira reaction.