Synthesis of Some 2'-C-Alkyl Derivatives of 9-(2-Phosphonomethoxyethyl)adenine and Related Compounds

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Title:Synthesis of Some 2'-C-Alkyl Derivatives of 9-(2-Phosphonomethoxyethyl)adenine and Related Compounds
Creators:
Dvořáková, Hana
Holý, Antonín
Rosenberg, Ivan
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 59, 9, pp. 2069-2094

Abstract

<p>To study the effect of β-substitution in 2'-alkyl derivatives of 9-(2-phosphonomethoxyethyl)adenine (<i>Ia</i>) on the antiviral activity or group specificity, these derivatives were synthesized. 9-(2-Hydroxyalkyl)adenines <i>VIII</i> were prepared by alkylation of adenine with suitably substituted oxiranes <i>XIII</i> or 2-hydroxyalkyl <i>p</i>-toluenesulfonates <i>IV</i> and <i>VI</i>. After protection of the adenine amino group by benzoylation (compounds <i>IX</i>) or amidine formation (compounds <i>X</i>), the intermediates were alkylated with diisopropyl <i>p</i>-toluenesulfonyloxymethanephosphonate (<i>XI</i>) in the presence of sodium hydride. After deprotection, the obtained phosphonate diesters <i>XII</i> were converted into phosphonic acids <i>I</i> by transsilylation and hydrolysis. This synthetic scheme was used for the preparation of ethyl (<i>Ie</i>), propyl (<i>If</i>), 2-propyl (<i>Ig</i>), 2-methylpropyl (<i>Ih</i>), cyclopropyl (<i>Ii</i>), cyclohexyl (<i>Ij</i>), benzyl (<i>Ik</i>) and phenyl (<i>Il</i>) derivatives. The 2'-trifluoromethyl derivative <i>XXIIa</i> was prepared analogously from 9-(2-hydroxy-3,3,3-trifluoropropyl)adenine (<i>XXa</i>), obtained by alkylation of adenine sodium salt with 2-hydroxy-3,3,3-trifluoropropyl bromide. 2'-Trimethylsilyl derivative <i>XIXa</i> was obtained by alkylation of adenine with 2-diisopropylphosphonomethoxy-3-(4-toluenesulfonyloxy)propyltrimethylsilane (<i>XVII</i>) followed by transsilylation and hydrolysis of diester <i>XVIIIa</i>. 2,6-Diaminopurine derivatives <i>XVIIId</i> and <i>XXIIb</i> were obtained analogously. 9-(3-Phosphonomethoxybutyl)adenine (<i>XXVIII</i>) and 9-(2-methyl-2-phosphonomethoxypropyl)adenine (<i>XXXV</i>) were prepared from the corresponding hydroxy derivatives <i>XXVIb</i> and <i>XXXII</i>, respectively, by the same reaction pathway as derivatives <i>I</i>.

Title:Synthesis of Some 2'-C-Alkyl Derivatives of 9-(2-Phosphonomethoxyethyl)adenine and Related Compounds
Creators:
Dvořáková, Hana
Holý, Antonín
Rosenberg, Ivan
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:59
Number:9
Page Range:pp. 2069-2094
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19942069UNSPECIFIED
ID Code:632
Item Type:Article
Deposited On:06 Feb 2009 17:02
Last Modified:06 Feb 2009 16:02

Citation

Dvořáková, Hana; Holý, Antonín; Rosenberg, Ivan (1994) Synthesis of Some 2'-C-Alkyl Derivatives of 9-(2-Phosphonomethoxyethyl)adenine and Related Compounds. Collection of Czechoslovak Chemical Communications, 59 (9). pp. 2069-2094. ISSN 0010-0765

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