Synthesis and anti-herpes simplex activity of analogues of phosphonoacetic acid

Abstract

The synthesis of monoesters (P and C) of phosphonoacetic acid (PA) is given. The carboxyl esters were prepared by two methods: the reaction of chloroacetates with tris(trimethylsilyl) phosphite, followed by hydrolysis; and by the acid-catalyzed esterification of PA with the appropriate alcohol. P-Monoesters of PA were prepared either by the reaction of alkyl[bis(trimethylsilyl)] phosphite with benzyl chloroacetate followed by deprotection or by the reaction of dimethylphenyl phosphite with benzyl bromoacetate followed by hydrogenolysis. Three aryl- (alkyl-)phosphinic acid derivatives are reported. The above compounds were evaluated for anti-herpes activity against HSV-induced DNA polymerase and in animals infected with herpes dermatitis.