Preparation of Phosphonomethyl Ethers Derived from 2-Phenylethanol and Its Amino Derivatives

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Title:Preparation of Phosphonomethyl Ethers Derived from 2-Phenylethanol and Its Amino Derivatives
Creators:
Krečmerová, Marcela
Holý, Antonín
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 60, 4, pp. 659-669

Abstract

<p>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 alcohols. 2-(3-Aminophenyl)ethanol was prepared from 3-nitrobenzoyl chloride using the Arndt-Eistert reaction. The primarily formed diazoketone <i>Ia</i> was converted into ethyl 3-nitrophenylacetate (<i>IIa</i>) which on catalytic hydrogenation afforded ethyl 3-aminophenylacetate (<i>IIIa</i>). Compound <i>IIIa</i> was reduced with lithium aluminium hydride to give 2-(3-aminophenyl)ethanol (<i>IVa</i>). 2-(3,5-Diaminophenyl)ethanol (<i>IVb</i>) was prepared analogously from 3,5-dinitrobenzoyl chloride. After protection of the amino group with dimethylaminomethylene group, the alcohol IVa was converted to diisopropyl 2-(3-aminophenyl)ethoxymethylphosphonate (<i>XII</i>) by reaction with sodium hydride and diisopropyl <i>p</i>-toluenesulfonyloxymethanephosphonate, followed by deprotection of the amino group by treatment with ammonia. Reaction of diisopropyl ester <i>XII</i> with bromotrimethylsilane gave free 2-(3-aminophenyl)ethoxymethylphosphonic acid (<i>XVII</i>). The same procedure, applied to the corresponding aminophenethyl alcohols, afforded: 2-(4-aminophenyl)ethoxymethylphosphonic acid (<i>XVI</i>) and 2-(3,5-diamino phenyl)ethoxymethylphosphonic acid (<i>XVIII</i>). The synthesized compounds were tested in vitro on cell cultures for the cytostatic and antiviral activity (HSV-1, HSV-2, VSV, VZV, CMV). No antiviral activity has been found for any of the compounds.

Title:Preparation of Phosphonomethyl Ethers Derived from 2-Phenylethanol and Its Amino Derivatives
Creators:
Krečmerová, Marcela
Holý, Antonín
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:60
Number:4
Page Range:pp. 659-669
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19950659UNSPECIFIED
ID Code:754
Item Type:Article
Deposited On:06 Feb 2009 17:03
Last Modified:06 Feb 2009 16:03

Citation

Krečmerová, Marcela; Holý, Antonín (1995) Preparation of Phosphonomethyl Ethers Derived from 2-Phenylethanol and Its Amino Derivatives. Collection of Czechoslovak Chemical Communications, 60 (4). pp. 659-669. ISSN 0010-0765

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