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

Hitesh Kumar Agarwal, Keykavous Parang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)317-322
Number of pages6
JournalNucleosides, Nucleotides and Nucleic Acids
Volume26
Issue number3
DOIs
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

Solid-Phase Synthesis Techniques
Hydroxyl Radical
Polymers
Trifluoroacetic Acid
Sodium Hydroxide
Fluorination
Halogenation
Thymidine
Purification
Substitution reactions
Resins
alovudine

Keywords

  • FLT
  • Solid-phase synthesis
  • Trityl resin

ASJC Scopus subject areas

  • Genetics
  • Biochemistry

Cite this

Application of solid-phase chemistry for the synthesis of 3′-fluoro-3′-deoxythymidine. / Agarwal, Hitesh Kumar; Parang, Keykavous.

In: Nucleosides, Nucleotides and Nucleic Acids, Vol. 26, No. 3, 03.2007, p. 317-322.

Research output: Contribution to journalArticle

Agarwal, Hitesh Kumar ; Parang, Keykavous. / Application of solid-phase chemistry for the synthesis of 3′-fluoro-3′-deoxythymidine. In: Nucleosides, Nucleotides and Nucleic Acids. 2007 ; Vol. 26, No. 3. pp. 317-322.
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