Sythesis Of New Analogs Of N-O Bond Containing Acyclic Nucleoside Phosphonate As Antivirus Agent

Analogs of acyclic nucleoside phosphonate demonstrated high and broad- spectrum of activity against DNA viruses and retroviruses. We designed a new type of acyclic nucleoside phosphonates. The structures of the new componds contain their strctural feature, namely the group of methoxyphosphonate, but it is unique because of the N-O bond.Diethylphosphite and paraformaldehyde are used as the start materials, after hydroxymethylation and sulphonyl reaction got sulfo-group containing phosphonate. Then reacted with N-hydroxyphthlimide got N-(methoxyphosphonate diethylester) phthlimide, which after hydrazine hydrolysis gave N-(methoxyphosphonate diethylester)amide. The amide was acylated with five acyl chloride got five N-(methoxyphosphonate diethylester)acylamide.Adenine, Uridine and Thymine were first hydroxyethylated to get the corresponding 2-hydroxyethyl nucleoside which then be chlorided with dichlorosulfoxide or tosyl chloride to gave 9-N-(2-chloroethyl)adenine, 1-N-(2-chloroethyl)uridine and 1-N-(2-chloroethyl)thymine. Uridine was first treated by HMDS then alkylated with 1,6-dibromohexyl gave 1-N-(6-bromohexyl)uridine. In the connect reaction, three routes have been tried and it was found that only N-alkylation is feasible. N-(methoxyphosphonate diethylester)acylamide connect with 9-N-(2-chloroethyl)adenine gave four new compond, with 1-N-(6-bromohexyl)uridine gave six new compond, with 1-N-(2-chloroethyl)thymine gave intramolecular cyclic compond.Hydrolysis of the target compond in trimethylbromosilane failed.