Synthesis and antiviral activities of amide derivatives containing the alpha-aminophosphonate moiety

Starting from (substituted-)benzaldehydes, the title compounds 6 were synthesized through five step reactions. Benzaldehydes were treated with ammonium hydroxide, followed by dialkyl phosphite, to give dialkyl N-(arylmethylene)-1-amino-1-aryl methylphosphonates ( 3). Phosphonates 3 were then easily hydrolyzed to give dialkyl 1-amino-1-aryl-methylphosphonates 5. Target compounds 6 were then obtained by the reaction of 5 and substituted benzoic or cinnamic acid. Their structures were clearly verified by spectroscopic data (IR, 1H, 13C, and 31P NMR, and elemental analysis). These compounds were shown to be antivirally active in the bioassay. It was found that title compounds 6g, 6l, and 6n had the same inactivation effect of TMV (EC 50 = 54.8, 60.0, and 65.2 microg/mL, respectively) as commercial product Ningnanmycin (EC50 = 55.6 microg/mL). To the best of our knowledge, this is the first report on the synthesis and antiviral activity of amide derivatives containing an alpha-aminophosphonate moiety.