M. Krecmerova et A. Holy, PREPARATION OF PHOSPHONOMETHYL ETHERS DERIVED FROM 2-PHENYLETHANOL AND ITS AMINO DERIVATIVES, Collection of Czechoslovak Chemical Communications, 60(4), 1995, pp. 659-669
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.