Synthesis and anti-HIV activities of bis-(cycloSaligenyl) pronucleotides derivatives of 3′-fluoro-3′-deoxythymidine and 3′-azido- 3′-deoxythymidine

Yousef Ahmadibeni, Rakesh Tiwari, Chelsie Swepson, Jui Pandhare, Chandravanu Dash, Gustavo F. Doncel, Keykavous Parang

Research output: Contribution to journalArticle

Abstract

Anti-HIV nucleoside monophosphates have limited cellular uptake due to the presence of negatively-charged phosphate group. Bis-(cycloSaligenyl) derivatives containing two anti-HIV nucleosides, 3′-fluoro-3′-deoxythymidine (FLT) and 3′-azido-3′-deoxythymidine (AZT) were synthesized to increase intracellular delivery of nucleoside monophosphates. 2,5-Bis(hydroxymethylene)benzene-1,4-diol was selected as a monocyclic bidentate scaffold and synthesized by three different methods from bis(hydroxymethylene) cyclohexan-1,4-diene-1,4-diol, or diethyl 2,5-dihydroxyterephthalate. The reaction of the tetraol with diisopropylphosphoramidous dichloride in the presence of 2,6-lutidine, followed by conjugation reactions with nucleosides (i.e., FLT and AZT) and oxidation afforded symmetrical and unsymmetrical bis-(cycloSaligenyl) diphosphate triester products, AZT-AZT, FLT-FLT, and FLT-AZT conjugates, in 63-74% overall yields and modest anti-HIV activities (IC50 = 2.8-69.6 μM).

Original languageEnglish (US)
Pages (from-to)802-805
Number of pages4
JournalTetrahedron Letters
Volume52
Issue number7
DOIs
StatePublished - Feb 16 2011
Externally publishedYes

Keywords

  • Anti-HIV
  • AZT
  • Bis-(cycloSaligenyl)
  • FLT
  • Nucleosides

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Fingerprint Dive into the research topics of 'Synthesis and anti-HIV activities of bis-(cycloSaligenyl) pronucleotides derivatives of 3′-fluoro-3′-deoxythymidine and 3′-azido- 3′-deoxythymidine'. Together they form a unique fingerprint.

  • Cite this