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

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 unsy

SUBMITTER: Ahmadibeni Y 

PROVIDER: S-EPMC4675361 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature