Application of solid-phase chemistry for the synthesis of 3'-fluoro-3'-deoxythymidine

Nucleosides Nucleotides Nucleic Acids. 2007;26(3):317-22. doi: 10.1080/15257770701257608.

Abstract

Reported solution-phase methods for the synthesis of 3'-fluoro-3'-deoxythymidine (FLT) are cumbersome, require purification of intermediates, and include several protecting/deprotecting steps. To circumvent these problems, a solid-phase strategy was designed for the synthesis of FLT. Thymidine was immobilized on trityl resin via the 5'-hydroxyl group. The subsequent mesylation of the free 3'-hydroxyl group in the presence of methanesulfonyl chloride afforded the polymer-bound 3'-O-mesylthymidine. Nucleophilic substitution of the mesyl moiety by hydroxyl group in the presence of sodium hydroxide produced the polymer-bound threothymidine. Fluorination with diethylaminosulfur trifluoride followed by acidic cleavage of the polymer-bound FLT in the presence of trifluoroacetic acid afforded FLT.

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Chemistry, Pharmaceutical / methods*
  • Dideoxynucleosides / chemical synthesis*
  • Dideoxynucleosides / chemistry*
  • Drug Design
  • Models, Chemical
  • Molecular Structure
  • Polymers / chemistry
  • Thymidine / chemistry
  • Trifluoroacetic Acid / chemistry
  • Zidovudine / analogs & derivatives

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides
  • Polymers
  • Zidovudine
  • Trifluoroacetic Acid
  • alovudine
  • Thymidine