Synthesis of Acyclic Adenine 8,N-Anhydronucleosides

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Title:Synthesis of Acyclic Adenine 8,N-Anhydronucleosides
Creators:
Meszárosová, Kateřina
Holý, Antonín
Masojídková, Milena
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 65, 7, pp. 1109-1125
Uncontrolled Keywords:Purines, Cyclizations, Nucleosides, Diazepines, Acyclic nucleoside analogues, Anhydronucleosides

Abstract

9-(4-Hydroxybutyl)adenine (<strong>10</strong>) was obtained by reaction of adenine with 4-[(2-tetrahydropyran-2-yl)oxy]butyl chloride (<strong>7</strong>) in the presence of DBU. 8-Bromo-9-(4-hydroxybutyl)adenine (<strong>13</strong>) was prepared by bromination of <strong>10</strong> or by alkylation of 8-bromoadenine (<strong>11</strong>) with 4-bromoethyl acetate followed by methanolysis. Tosylation of compound <strong>13</strong> afforded the 4-tosyloxy derivative <strong>15</strong> which gave on heating with methylamine or cyclopropylamine 6-methyl- (<strong>17a</strong>) or 6-cyclopropyl-7,8,9,10-tetrahydro-6<i>H</i>-[1,3]diazepino[1,2-<i>e</i>]purin-4-amine (<strong>17b</strong>), while the reaction with hydrazine afforded 7,8,9,10-tetrahydro-6<i>H</i>-[1,3]diazepino[1,2-<i>e</i>]purine-4,6-diamine (<strong>17d</strong>). Treatment of compound <strong>13</strong> with thionyl chloride gave 9-(4-chlorobutyl)-8-chloroadenine (<strong>18</strong>) as the main product which was transformed to <strong>17b</strong>, 6-propyl-7,8,9,10-tetrahydro-6<i>H</i>-[1,3]diazepino[1,2-<i>e</i>]purin-4-amine (<strong>17c</strong>) or 7,8,9,10-tetrahydro-6<i>H</i>-[1,3]diazepino[1,2-<i>e</i>]purin-4-amine (<strong>17e</strong>) by reaction with cyclopropylamine, propylamine or ammonia, respectively. Compound <strong>17e</strong> was quite stable both in acid and alkaline solutions, at room temperature or at 90 °C. Compound <strong>13</strong> was converted to 9-(4-hydroxybutyl)-8-methylaminoadenine (<strong>19</strong>) by reaction with methylamine. Compound <strong>19</strong> failed to undergo intramolecular cyclization to diazepine <strong>17a</strong> on treatment with diphenyl carbonate, bis(4-nitrophenyl) carbonate or 1,1'-carbonyldiimidazole. <p>

Title:Synthesis of Acyclic Adenine 8,N-Anhydronucleosides
Creators:
Meszárosová, Kateřina
Holý, Antonín
Masojídková, Milena
Uncontrolled Keywords:Purines, Cyclizations, Nucleosides, Diazepines, Acyclic nucleoside analogues, Anhydronucleosides
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:65
Number:7
Page Range:pp. 1109-1125
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20001109UNSPECIFIED
ID Code:1704
Item Type:Article
Deposited On:06 Feb 2009 17:11
Last Modified:06 Feb 2009 16:12

Citation

Meszárosová, Kateřina; Holý, Antonín; Masojídková, Milena (2000) Synthesis of Acyclic Adenine 8,N-Anhydronucleosides. Collection of Czechoslovak Chemical Communications, 65 (7). pp. 1109-1125. ISSN 0010-0765

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