Synthesis and Biological Effects of Acyclic Analogs of Deazapurine Nucleosides

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Title:Synthesis and Biological Effects of Acyclic Analogs of Deazapurine Nucleosides
Creators:
Dvořáková, Hana
Holý, Antonín
Votruba, Ivan
Masojídková, Milena
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 58, 3, pp. 629-648

Abstract

Deaza analogs of three basic types of S-adenosyl-L-homocysteine hydrolase (SAHase) inhibitors, (<i>S</i>)-DHPA (<i>I</i>), eritadenine (<i>II</i>) and AHPA (<i>III</i>), were prepared. Alkylation of 3-deazaadenine (<i>V</i>), 3-deazapurine (<i>VI</i>), 1-deazaadenine (<i>VII</i>) and 4-amino-6-bromo-5-cyanopyrrolo[2,3-<i>d</i>]pyrimidine (<i>XXII</i>) with (<i>R</i>)-2,2-dimethyl-4-tosyloxymethyl-1,3-dioxolane (<i>XIIIb</i>), followed by acid hydrolysis, afforded the corresponding (<i>S</i>)-2,3-dihydroxypropyl derivatives <i>XVIIa -XIXa</i> and <i>XXV</i>. Reaction of <i>V</i> and <i>VII</i> with 2,3-<i>O</i>-cyclohexylidene-D-erythrono lactone (<i>XXIX</i>) and subsequent removal of the protecting groups in an acid medium gave eritadenine analogs <i>XXVII</i> and <i>XXVIII</i>. Compounds <i>V</i> and <i>VII</i> were alkylated with bromoacetaldehyde diethyl acetal to give <i>N</i>-(2,2-diethoxyethyl) derivatives <i>XXXII</i> and <i>XXXIII</i> from which the substituted acetaldehyde derivatives were liberated in situ and converted into compounds <i>XXX</i> and <i>XXXI</i> by cyanohydrine reaction followed by acid hydrolysis. The alkylations were performed in dimethylformamide with sodium or cesium salts of the bases. Biological activity was observed only with 3-deazaadenine derivatives <i>XVIIa, XXVII</i> and <i>XXX</i>, which exhibit both enzyme-inhibitory and antiviral activities.

Title:Synthesis and Biological Effects of Acyclic Analogs of Deazapurine Nucleosides
Creators:
Dvořáková, Hana
Holý, Antonín
Votruba, Ivan
Masojídková, Milena
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:3
Page Range:pp. 629-648
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19930629UNSPECIFIED
ID Code:187
Item Type:Article
Deposited On:06 Feb 2009 16:58
Last Modified:06 Feb 2009 15:59

Citation

Dvořáková, Hana; Holý, Antonín; Votruba, Ivan; Masojídková, Milena (1993) Synthesis and Biological Effects of Acyclic Analogs of Deazapurine Nucleosides. Collection of Czechoslovak Chemical Communications, 58 (3). pp. 629-648. ISSN 0010-0765

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