The fluorescent N-unsubstituted 1,2,3-triazol-4-yl analogues of the nucleic acid bases (i.e. 5-TrzdU, 5-TrzdC, 8-TrzdA and 8-TrzdG; Figure 1) have been synthesized by metal-catalyzed reactions between the 5-ethynylpyrimidine or 8-ethynylpurine nucleosides with trimethylsilyl azide (TMS-N3). CuI catalyzed cycloaddition (DMF/H2O, 90 oC, 5 h) gave 1,2,3-triazoles as sole products however in low to moderate yield (10% for 5-TrzdC, 50% for 5-TrzdU) due to the oxidation of Cu (I) to Cu (II) during the reaction. Combination of CuSO4/sodium ascorbate gave triazoles in improved yields (38% for 5-TrzdC and 52% for 5-TrzdU). Interestingly, Ag2CO3 catalyzed cycloaddition (DMF, 2 eq. H2O, 80 oC, 1 h) of 8-ethynylpurine nucleosides with TMS-N3 produced 8-triazolylpurines as sole products in good yields (8-TrzdG, 55%), while analogous cycloadditions of 5-ethynylpyrimidine nucleosides produced mixture of 5-triazolylpyrimidine nucleosides (5-TrzdC, 7%) and the corresponding 5-(1-azidovinyl)pyrimidine byproducts (5-(1-azidovinyl)-2'-deoxycytidine, 48%). The novel N-unsubstituted 1,2,3-triazol-4-yl nucleosides analogues showed excellent fluorescent properties in MeOH. The 8-purine analogue 8-TrzdA exhibits the highest quantum yield of 44% while the 8-TrzdG had quantum yield of 9%. The 5-pyrimidine analogues 5-TrzdU and 5-TrzdC showed a large Stokes shift of ~110 nm with the maximum emission approximately at 408 nm and quantum yield of 2%. The application of these fluorescent nucleosides with the minimalistic modification at heterocyclic bases to cell imaging and DNA modifications will be discussed.

5-Pyrimidine and 8-purine nucleosides modified with unsubstituted 1,2,3-triazol-4-yl: Synthesis and fluorescent properties

255th National Meeting (2018)

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