Synthesis of cinnamate ester-AZT conjugates as potential dual-action HIV-1 integrase and reverse transcriptase inhibitors

Synthetic approaches to a series of novel cinnamate ester-AZT conjugates have been explored and a successful pathway has finally been developed. alpha-(Halomethyl)cinnamate esters, obtained in high yield by treating benzyl-protected salicylaldehde-derived Baylis-Hillman adducts with acetyl bromide at low temperature, have been treated with propargylamine to afford substrates for click chemistry reactions with azidothymidine (AZT) in the presence of in situ generated Cu(I) catalyst to produce the title compounds. (C) 2014 Elsevier Ltd. All rights reserved.