Synthesis of four new 3-imidazolyl-2-azidoacrylate derivatives bearing biphenyl tetrazole moiety as potential angiotensin II receptor antagonist

Abstract

Background: The renin angiotensin system which is stimulated by angiotensin II, leads to increase in blood pressure. An angiotensin II receptor antagonist can control effectively hypertension. Synthesis of new compounds that have the key structural elements present in angiotensin receptor antagonists is of interest. Herein, we report the synthesis of novel Alkyl 2-azido-3-[1- [[2?-(tetrazol-5-yl) biphenyl-4-yl]methyl]-2-alkylimidazolyl]acrylate (4 and 6). Methods: 2-Alkyl-4(5)-hydroxymethylimidazoles were synthesized via Weidenhagen reaction using copper salt, an aldehyde, dihydroxyacetone and concentrated ammonium hydroxide. 2-Alkyl-4(5)-hydroxymethylimidazoles were oxidized by heating with MnO2 in CH2Cl2: dioxane to its carboxaldehyde derivatives. The carboxaldehyde derivatives were reacted with tritylated [4?-(bromomethyl) biphenyl-2-yl]tetrazole in presence of potassium carbonate to give two regioisomers 1 & 2 that separated by column chromatography. The regioisomers 1 & 2 were employed in the synthesis of 2-azidoacrylate derivatives 3 & 5 using sodium alkoxide and alkyl ?-azidoacetate. Consequently, the protecting group of tetrazole was removed by stirring the compound 3 and 5 in 10% hydrochloric acid solution at room temperature. Results: The regioisomers 1 & 2 were separated chromatographically in 1:3 proportions using 70: 30 toluene: ethyl acetate as eluent, respectively. The alkyl 3-substituted imidazol-2-azido acrylate derivatives were synthetized as oily form in 19-25% yield. The deprotection of tetrazole was afforded light yellow oily final compounds in 60-65% yield. Conclusion: Four new alkyl ?-azidoacrylate derivatives bearing biphenyl tetrazole moiety were synthetized via Knoevenagel condensation. The protecting group was removed in acidic media to afford final compounds 4 and 6. The chemical structures of synthesized compounds were characterized by FT-IR and 1HNMR spectroscopies. Copyright ط¢آ© 2013 by Tabriz University of Medical Sciences.