PREPARATION OF PHOSPHONOMETHYL ETHERS DERIVED FROM 2-PHENYLETHANOL AND ITS AMINO DERIVATIVES

A series of compounds derived from the acyclic nucleoside antiviral 9- (2-phosphonomethoxyethyl)adenine (PMEA), in which the adenine ring is replaced by phenyl, 4-aminophenyl, 3-aminophenyl or 3,5-diaminophenyl group, has been prepared starting from the corresponding phenethyl alc ohols. 2-(3-Aminophenyl)ethanol was prepared from 3-nitrobenzoyl chlor ide using the Amdt-Eistert reaction. The primarily formed diazoketone Ia was converted into ethyl 3-nitrophenylacetate (IIa) which on cataly tic hydrogenation afforded ethyl 3-aminophenylacetate (IIIa). Compound IIIa was reduced with lithium aluminium hydride to give 2-(3- aminoph enyl)ethanol (IVa). 2-(3,5-Diaminophenyl)ethanol (IVb) was prepared an alogously from 3,5-dinitrobenzoyl chloride. After protection of the am ino group with dimethylaminomethylene group, the alcohol IVa was conve rted to diisopropyl 2-(3-aminophenyl)ethoxymethylphosphonate (XII) by reaction with sodium hydride and diisopropyl p-toluenesulfonyloxymetha nephosphonate followed by deprotection of the amino group by treatment with ammonia. Reaction of diisopropyl ester XII with bromotrimethylsi lane gave free 2-(3-aminophenyl)ethoxymethylphosphonic acid (XVII). Th e same procedure, applied to the corresponding aminophenethyl alcohols , afforded: 2-(4-aminophenyl)ethoxymethylphosphonic acid (XVI) and 2-( 3,5-diaminophenyl)ethoxymethylphosphonic acid (XVIII). The synthesized compounds were tested in vitro on cell cultures for the cytostatic an d antiviral activity (HSV-1, HSV-2, VSV, VZV, CMV). No antiviral activ ity has been found for any of the compounds.