The Synthesis And Properties Of New Fluorescent Nucleoside Analogs

Fluorescence nucleoside analogs, which can photophysically signal the changes in the microenvironment, are widely applied in investigation of structure and function of nucleic acids. When strategically incorporated into the nucleic acid strands, fluorescence nucleoside analogs, whose structures are similar to the nature nucleoside, minimally perturb the native structure and function of the target nucleic acid.In this thesis, four base-modified fluorescent nucleoside analogs, whose photophysical properties were investigated by UV-Vis absorption and fluorescence, were synthesized. Meanwhile, synthesis of 5-(2-pyrrolyl) uridine analog was investigated in six different conditions. The results show that it’s really hard to obtain the pure target product 5-(2-pyrrolyl) uridine analog, due to its instability. Further work should be done to know about its chemical and photophysical property.The thieno[2,3-d]pyrimidine was synthesized in two steps using p-dithiane-2,5-diol and methyl cyanoacetate as the raw materials. The target compound, thieno[2,3-d] uridine analog, was obtained by alcoholysis of the product from the reaction of β-D-ribofuranose 1-acetate 2,3,5-tribenzoate and the pyrimidine analog. Thieno[2,3-d] uridine analog, displaying emission maxima at 340 nm, has a great sensibility to solvent polarity and viscosity.Using ethyl isocyanoacetate and ethoxycarbonyl isothiocyanate as the raw materials, thiazole[5,4-d]pyrimidine was gained via three-step reaction. Alcoholysis of the product from the reaction of β-D- ribofuranose 1-acetate 2,3,5-tribenzoate and the pyrimidine analog gave the target product thiazole[2,3-d]uridine analog. Thiazole[2,3-d] uridine analog is sensitive to solvent polarity, p H and viscosity, because the nitrogen atom enhances the solvation effect.Target boronic acids were achieved by the reaction of 4-bromotoluene with trimethylborate or trimethoxylborate in the given condition. The target product, 5-(4-methylbenzene) uridine analog and 5-(4-methoxylbenzene) uridine analog, were synthesized from boronic acid and 5-Iodouridine by one step. 5-(4-methylbenzene) uridine analog was only found to be sensitive to p H. 5-(4-Methoxyl- benzene) uridine analog was sensitive to solvents, pH and viscosity.Since their fluorescence intensity is not quenched by other nucleosides, it means that all four analogs will not be influenced by adjacent nucleotide, they can act as flurescence probes.Comparing the photophysical properties of all four fluorescent nucleoside analogs, we have proved that atom in strong electric negative can enhance the sensitivity of fluorescence nucleoside analogs to environmental changes, so that it has more ideal optical physical properties, and more in line with the characteristics of fluorescent probes.In brief, thiazole [5,4-d] uridine analogs and 5-(4-methoxy benzene) uridine analogs have the most ideal photophysical property, which is sensitive to changes in the environment, and comply with the requirements of the fluorescent probe.