Abstract |
The synthesis of stable and potentially bioactive xylofuranosyl nucleoside analogues and potential sugar diphosphate or nucleotide mimetics comprising a 1,2,3-triazole moiety is reported. 3 -O-Methyl-branchedN-benzyltriazole isonucleosides were accessed in 5-7 steps and 42-54 \% overall yields using a Cu(I)-catalyzed cycloaddition of 3-O-propargyl-1,2-O-isopropylidene-alpha-D-xylofuranose with benzyl azide as key step. Related isonucleotides were obtained by 5-O-phosphorylation of acetonide-protected 3-O-propargyl xylofuranose and further click cycloaddition or by Staudinger-phosphite reaction of a 5-azidoN-benzyltriazole isonucleoside. Hydroxy-, amino- or bromomethyl triazole 5 -isonucleosides were synthesized by thermal cycloaddition of 5-azido 3-O-benzyl/dodecyl xylofuranoses with propargyl alcohol, propargylamine or propargyl bromide. Better yields (82-85 \%) were obtained when using propargyl alcohol and a high 1,4-regioselectivity was attained with propargyl bromide. FurtherO/N-phosphorylation or Arbuzov reaction led to (triazolyl)methyl phosphates, phosphoramidates or phosphonates. The latter were converted into uracil nucleoside 5 -(triazolyl)methyl phosphonates as prospective nucleoside diphosphate mimetics. |