Synthesis and Biological Effects of 9-(3-Hydroxy-2-phosphonomethoxypropyl) Derivatives of Deazapurine Bases

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Title:Synthesis and Biological Effects of 9-(3-Hydroxy-2-phosphonomethoxypropyl) Derivatives of Deazapurine Bases
Creators:
Dvořáková, Hana
Holý, Antonín
Alexander, Petr
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 58, 6, pp. 1403-1418

Abstract

Analogs of antiviral 9-(<i>S</i>)-(3-hydroxy-2-phosphonomethoxypropyl)adenine (HPMPA, <i>I</i>), containing modified purine bases 3-deazaadenine <i>XII</i>, 1-deazaadenine <i>XIV</i>, 7-deaz-7-cyanoaadenine <i>XXXII</i> and 3-deazaguanine <i>XXXVIII</i>, were prepared by alkylation of the bases with synthon <i>XVII</i>, containing preformed structure of the side chain, in the presence of cesium carbonate. The obtained protected derivatives were deblocked successively with sodium methoxide and bromotrimethylsilane to give phosphonic acids <i>XII, XIV, XXXII</i> and <i>XXXVIII</i>. Compounds <i>XII, XIV</i> and <i>XVI</i> were also prepared from (<i>S</i>)- or (<i>R</i>)-9-(2,3-dihydroxypropylderivatives <i>VI, VII</i> and <i>XV</i> by the reaction with chloromethanephosphonyl dichloride, isomerization of the arising 2'- and 3'-chloromethanephosphonates and conversion of the 3'-isomers into the phosphonic acids in alkaline medium. The 3-deaza analog <i>XII</i> was also prepared by ditritylation of <i>VI</i>, reaction with bis(2-propyl) tosyloxymethanephosphonate (<i>XXII</i>), subsequent acid hydrolysis and reaction with bromotrimethylsilane. 3-DeazaHPMPA (<i>XII</i>) is a potent inhibitor of DNA viruses (HSV-1, HSV-2, VZV, CMV) and exhibits activity against <i>Plasmodium sp.</i>

Title:Synthesis and Biological Effects of 9-(3-Hydroxy-2-phosphonomethoxypropyl) Derivatives of Deazapurine Bases
Creators:
Dvořáková, Hana
Holý, Antonín
Alexander, Petr
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:58
Number:6
Page Range:pp. 1403-1418
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19931403UNSPECIFIED
ID Code:259
Item Type:Article
Deposited On:06 Feb 2009 16:59
Last Modified:06 Feb 2009 15:59

Citation

Dvořáková, Hana; Holý, Antonín; Alexander, Petr (1993) Synthesis and Biological Effects of 9-(3-Hydroxy-2-phosphonomethoxypropyl) Derivatives of Deazapurine Bases. Collection of Czechoslovak Chemical Communications, 58 (6). pp. 1403-1418. ISSN 0010-0765

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