Nucleoside Azide-Alkyne Cycloaddition Reactions Under Solvothermal Conditions or Using Copper Vials in a Ball Mill

Nucleosides Nucleotides Nucleic Acids. 2015;34(5):361-70. doi: 10.1080/15257770.2014.1001855.

Abstract

Novel nucleoside analogues containing photoswitchable moieties were prepared using 'click' cycloaddition reactions between 5'-azido-5'-deoxythymidine and mono- or bis-N-propargylamide-substituted azobenzenes. In solution, high to quantitative yields were achieved using 5 mol% Cu(I) in the presence of a stabilizing ligand. 'Click' reactions using the monopropargylamides were also effected in the absence of added cuprous salts by the application of liquid assisted grinding (LAG) in metallic copper reaction vials. Specifically, high speed vibration ball milling (HSVBM) using a 3/32″ (2.38 mm) diameter copper ball (62 mg) at 60 Hz overnight in the presence of ethyl acetate lead to complete consumption of the 5'-azido nucleoside with clean conversion to the corresponding 1,3-triazole.

Keywords: Synthetic methodology; green chemistry; modified nucleosides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry
  • Alkynes / chemistry*
  • Azo Compounds / chemistry*
  • Catalysis
  • Click Chemistry
  • Copper / chemistry
  • Cycloaddition Reaction
  • Ligands
  • Triazoles / chemical synthesis*
  • Zidovudine / analogs & derivatives*
  • Zidovudine / chemistry

Substances

  • Acetates
  • Alkynes
  • Azo Compounds
  • Ligands
  • Triazoles
  • Zidovudine
  • ethyl acetate
  • Copper