Fluorescent 5-Pyrimidine and 8-Purine Nucleosides Modified with an N-Unsubstituted 1,2,3-Triazol-4-yl Moiety

Abstract

The Cu(I)- or Ag(I)-catalyzed cycloaddition between 8-ethynyladenine or guanine nucleosides and TMSN3 gave 8-(1-H-1,2,3-triazol-4-yl) nucleosides in good yields. On the other hand, reactions of 5-ethynyluracil or cytosine nucleosides with TMSN3 led to the chemoselective formation of triazoles via Cu(I)-catalyzed cycloaddition or vinyl azides via Ag(I)-catalyzed hydroazidation. These nucleosides with a minimalistic triazolyl modification showed excellent fluorescent properties with 8-(1-H-1,2,3-triazol-4-yl)-2′-deoxyadenosine (8-TrzdA), exhibiting a quantum yield of 44%. The 8-TrzdA 5′-triphosphate was incorporated into duplex DNA containing a one-nucleotide gap by DNA polymerase β.

Extension of furopyrimidine nucleosides with 5-alkynyl substituent: Synthesis, high fluorescence, and antiviral effect in the absence of free ribose hydroxyl groups

“…The iodine attached to the furopyrimidine core quenched the emission of fluorescence almost completely for iodonucleoside 4 (Φ = 0.04), in line with identified halogen effect. 58 Overall, the quantum yields of alkynyl furopyrimidines are competitive with those of recently reported alkynyl fluorescent nucleosides, 59 , 60 and are even comparable with values for nucleosides labeled with auxiliary chromophores. 61 …”

Fundamental photophysics of isomorphic and expanded fluorescent nucleoside analogues

“…The heteroaryl-pyrimidine nucleosides had two absorption bands in water. In addition to the absorption of the pyrimidine chromophore at ~ 260 nm, there was a well-separated red-shifted absorption band centred at 291-325 nm, depending on the heterocyclic substituent 291,296 . A computational study showed that the red-shifted absorption band arose from π-π* electronic transitions in the planar conformation of the chromophores having expanded conjugated electronic system 297 .…”

Modified Nucleosides, Nucleotides and Nucleic Acids via Click Azide-Alkyne Cycloaddition for Pharmacological Applications

“…5-Ethynyl pyrimidine and 8-ethynyl purine nucleosides have been recently reacted with TMSN 3 via CuI or CuSO 4 /sodium ascorbate catalyzed cycloaddition to give chemoselectively the corresponding 5- and 8-triazolyl derivatives respectively [ 43 ]. The introduction of a simple triazole moiety resulted in good fluorescent properties.…”

“…In a recent work, Honcharenko et al [ 68 ] reported for the first time a method for the efficient conjugation of peptides to phosphorothioate oligonucleotides (PS-ON) ( Scheme 22 ). The use of phosphorothioate as a backbone is a widely employed strategy to enhance the pharmacokinetics and nuclease resistance of oligonucleotides [ 69 ], and to date, the majority of therapeutic ONs incorporate the PS backbone modification [ 43 ]. However, there are few examples of the successful use of the CuAAC conjugation to oligonucleotides with a substantial PS content, probably due to cleavage and desulfurization of PS linkages, which can occur in the presence of catalytic amounts of CuI [ 70 ].…”