Treatment of 2-decyloxy-3-(dodecylmercapto)-1-propanol (I) with phosphorus oxychloride in the presence of Et3N gave the intermediate dichlorophosphate ester (II). This was subsequently condensed with 3'-deoxy-3'-azidothymidine (AZT) (III) to produce, after aqueous hydrolysis, the target phosphate diester. The title diester was alternatively obtained by the phospholipase D-catalyzed condensation of AZT (III) with the choline monophosphate ester (IV).
In a further procedure, the monophosphate ester of 3-dodecylmercapto-2-decyloxy-1-propanol (V) was directly condensed with AZT employing DCC as the coupling reagent. A related method involved previous activation of (V) as the mixed anhydride with benzenesulfonyl chloride or triisopropylbenzenesulfonyl chloride in the presence of pyridine.