Synthesis and Antiviral Activities of Chiral Thiourea Derivatives Containing an α-Aminophosphonate Moiety

Starting from benzaldehyde 1, the title compounds 8 were synthesized in six steps. Benzaldehyde1 was reacted with ammonium hydroxide, and the resulting imine was then treated with dialkyl phosphite 3 to give dialkyl N-(arylmethylene)-1-amino-1-aryl methylphosphonates 4. Phosphonates 4 were then easily hydrolyzed to give dialkyl 1-amino-1-aryl-methylphosphonates 6, which on treatment with triethylamine, carbon disulfide, and phosphorus oxychloride provided 7. Target compounds 8 were then prepared by the reaction of 7 with substituted chiral amine. The structures were clearly verified by spectroscopic data (IR, 1H, 13C, and 31P NMR, and elemental analysis). The bioassay of these compounds revealed them as antivirally active. It was found that title compounds 8g, 8e, 8k, and 8m had the same curative effects of TMV (inhibitory rate = 54.8, 50.5, 50.4, and 50.4%, respectively) as the commercial product Ningnanmycin (56.2%). This would appear to be the first report of the synthesis and antiviral activity of chiral thiourea derivatives containing an α-aminophosphonate moiety.