Synthesis Of Novel Trifluoromethylated 1,2,3-Triazole Nucleoside Analogues Via Click Chemistry

Fluorine-containing nucleosides and analogues have drawn special attentions due to their unique properties. Currently, the development of new synthetic strategies for the regioselective introduction of fluorine(s) into naturally nucleosides and their analogues has become a challenge for organic chemists.The dissertation described herein focuses on the synthesis of novel trifluoromethylated 1,2,3-triazole nucleoside analogues via click chemistry. We have developed a straightforward method for the highly regioselective synthesis of 5-trifluoromethyl-1,2,3-triazole nucleoside analogues. This method highlighted the use of tert-butyldimethylsilyl (TBS) group as the directing group in the 1,3-dipolar cycloaddition reaction. 4-tert-Butyldimethylsilyl-5-trifluoromethyl-1,2,3-triazole nucleoside analogues were generated as the single cycloaddition products in moderate yields (15-70%) via the treatment of glycosyl azides with 3,3,3-trifluoro-1-tert-butyldimethylsilylpropyne in toluene at 85℃. Removal of TBS groups in these triazole cycloadducts with tetrabutylammonium fluoride (TBAF) smoothly afforded various 5-trifluoromethyl-1,5-disubstituted 1,2,3-triazole nucleoside analogues in good yields (40-88%). Finally, two 5-trifluoromethyl substituted 1,2,3-triazole nucleoside analogues were selected as the model substrates for the removal of the protecting groups in the sugar moieties. The biological activities evaluation of the obtained fluorinated 1,2,3-triazole nucleoside analogues is currently under investigation in our collaboration laboratory.