SummaryIn order to enhance the therapeutic efficacy of azidothymidine (AZT) by improving its pharmacoktnetlc properties, three prodrugs of AZTwere synthesized by esterifying the 5'-hydroxyl of AZT with three pharmacologically inactive steroidal 1713-carboxylic acids. Preliminary results of in vitro anti-HIV activity screening of the compounds show that~IJ' of these esters have anti-HIV activity comparable to that of AZT. This report discusses the synthesis and anti-HIV activity screening results of the prodrugs.

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Peracetylated alpha-D-glucose was coupled with silylated 5-chlorouracil. The product (2) was deacetylated and 4',6'-hydroxyls were then protected with 4',6'-O-isopropylidene group. Fluorine was introduced at the 3'-position, followed by acetylation, deprotection, tritylation, oxidation and deritylation of subsequent compounds gave the target compound (10).

1,2:5,6-Di-0-isopropylidene glucofuranose on mild oxidation, reduction, fluorination and deisopropylidenation followed by acetylation gave peracetylated 3-deoxy-3-fluoro-alpha-D-glucopyranose. This was coupled with silylated 5 fluorouracil. The nucleoside was deacetylated and after several subsequent protection and deprotection and final oxidation afforded the title compound.

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